Does prostatic ductal adenocarcinoma exist?

Prostatic ductal (endometrioid) adenocarcinoma has been considered a distinct pathologic and clinical entity since it was first described more than 30 years ago. Its current status as a unique neoplasm is controversial, however, because it has considerable histologic overlap with typical acinar adenocarcinoma, particularly in small specimens such as needle biopsies. There are also conflicting views regarding its clinical behavior. We recently encountered a series of typical peripheral zone cancers of the prostate gland with prominent papillary or cribriform pattern that apparently did not involve the large periurethral prostatic ducts or verumontanum. To determine the incidence of these "ductal features" in nonductal carcinoma, we reviewed the findings in 338 consecutive totally embedded whole-mount prostatectomy specimens with typical clinical and pathologic features of acinar carcinoma. We defined carcinoma with significant "ductal features" as one that displayed papillary or cribriform pattern involving an arbitrarily defined aggregate focus at least 5 mm in diameter. Anti-keratin 34beta-E12 immunohistochemical staining for basal cells allowed exclusion of areas of papillary or cribriform pattern of high-grade prostatic intraepithelial neoplasia. We identified carcinoma with ductal features (papillary or cribriform growth) in 17 prostatectomy specimens (5% of cases) exclusively in the peripheral zone without involving the periurethral region. Papillary pattern was present in 11 of these cases (65%) and cribriform pattern in 10 (59%), including 4 cases (24%) with both patterns. Of 11 needle biopsy specimens available for examination from these 17 cases, 4 (36%) contained at least focal papillary or cribriform pattern of carcinoma. We conclude that adenocarcinoma arising in the peripheral zone of the prostate gland may display ductal carcinoma features (papillary or cribriform growth) classically associated with ductal adenocarcinoma. These findings, together with the recognized near-constant association of prostatic ductal adenocarcinoma and typical prostate cancer, suggest that ductal adenocarcinoma results from spread of typical prostatic acinar carcinoma into the large accommodating periurethral ducts and stroma, and that there are no unique histologic features other than site of growth. Identification of papillary or cribriform growth of cancer in prostate needle biopsies usually results from peripheral zone adenocarcinoma and not ductal adenocarcinoma.     

Immunohistochemical stains for p63 and alpha-methylacyl-CoA racemase, versus a cocktail comprising both, in the diagnosis of prostatic carcinoma: a comparison of the immunohistochemical staining of 430 foci in radical prostatectomy and needle biopsy tissues

The diagnosis of prostatic carcinoma and especially minimal prostatic carcinoma can sometimes be challenging on needle core biopsy and occasionally immunohistochemistry is an aid in the diagnosis. Immunostains, such as those directed against the basal cell marker p63 and, more recently, employing antibodies reactive with alpha-methylacyl-CoA racemase (AMACR), can be useful in this situation. The aim of this investigation was to assess the diagnostic utility of a p63/AMACR antibody cocktail and compare the staining pattern it produces with that using the individual antibodies alone. A retrospective review of 31 consecutive radical prostatectomy specimens and 150 prostate needle biopsy samples was performed to select histologic sections showing foci of prostatic carcinoma and/or minimal prostatic carcinoma, high-grade prostatic intraepithelial neoplasia (HGPIN), as well as common benign mimickers of prostatic carcinoma, to include atrophy and basal cell hyperplasia, especially with prominent nucleoli. Serial histologic sections from the corresponding paraffin blocks were stained with hematoxylin and eosin and by immunostains for p63, AMACR, and a prediluted antibody cocktail comprising both. The diagnostic utility of the cocktail was assessed, and the staining characteristics it produced were compared with those using the individual immunostains. In 430 foci, the cocktail produced a p63 staining profile identical to that using the single p63 antibody. Distinction of the nuclear p63 signal from the cytoplasmic AMACR localization was readily accomplished. There was an excellent agreement (kappa=0.91; P<0.0001) between the AMACR staining profile using the cocktail and the single AMACR antibody alone. The cocktail was very useful in highlighting prostatic carcinoma associated with HGPIN, flat and cribriform HGPIN, and distorted foci of minimal prostatic carcinoma. These data indicate that use of a p63/AMACR cocktail is essentially equivalent to use of each antibody separately for immunohistochemical confirmation of a diagnosis of prostatic carcinoma in needle biopsy. This cocktail would be of diagnostic utility when only limited tissue is available for immunohistochemical evaluation of small, diagnostically difficult foci in prostate needle biopsy tissue.     

High-grade prostatic intraepithelial neoplasialike ductal adenocarcinoma of the prostate: a clinicopathologic study of 28 cases

Most of the prostatic ductal adenocarcinomas of the prostate are characterized by cribriform and/or papillary architecture lined by columnar pseudostratified malignant epithelium. We report 28 cases of ductal adenocarcinomas on needle biopsy and transurethral resection of prostate closely resembling high-grade prostatic intraepithelial neoplasia (HGPIN) composed of simple glands with flat, tufting, or micropapillary architecture. The mean age of the patients was 68 years (range, 50 to 91 y). Prostate specific antigen serum level at diagnosis ranged from 1.2 to 12.1 ng/mL. Treatment included radical prostatectomy (n=9), hormone therapy (n=7), radiotherapy (n=5), and cryotherapy (n=1). Three patients had recent biopsies without information on treatment and 3 patients were lost to follow-up after diagnosis. The number of cores involved by tumor in each case ranged from 1 to 18, with more than 1 core involved in 13 cases. Flat was the most common pattern (42%), followed by tufted (41%), and micropapillary (17%) (some with more than 1 pattern). Fourteen cases revealed segments of dilated gland on the edge of the biopsies, suggesting a large gland component. In radical prostatectomies, tumor was primarily composed of small (25%), medium (17%), or cystically dilated (58%) cancer glands, with all cases demonstrating a mixture of different gland sizes. Cytologically, tumors were characterized by tall columnar atypical cells, basally located nuclei, and amphophilic cytoplasm. The tumors lacked marked pleomorphism, necrosis, solid areas, cribriform formation, or true papillary fronds. Immunohistochemically, alpha-methyl acyl coenzyme-A racemase staining was seen in 93% of cases, with the majority showing strong and diffuse staining. No basal cells were present on p63 and/or high molecular weight cytokeratin staining. In the radical prostatectomy specimens, tumor volumes ranged from a small focus (less than 0.01 cm3) to 1.2 cm3. Concurrent conventional acinar Gleason score 6 adenocarcinomas were seen in 6 of the 9 radical prostatectomy cases, in all cases as separate nodules from the PIN-like ductal adenocarcinomas. Only one of the PIN-like ductal adenocarcinomas at radical prostatectomy had extraprostatic extension, which was focal. PIN-like ductal adenocarcinoma differs from HGPIN by the presence of cystically dilated glands, a greater predominance of flat architecture, and less frequently prominent nucleoli. Verification often requires the immunohistochemical documentation of the absence of basal cells in numerous atypical glands. Although usual ductal adenocarcinoma is considered comparable to Gleason score 8, PIN-like ductal adenocarcinoma was accompanied by Gleason score 6 acinar carcinoma and behaved similar to Gleason score 6 acinar cancer. Recognition of this entity is critical to differentiate it from both HGPIN and conventional ductal adenocarcinoma.     

Partial atrophy on prostate needle biopsy cores: a morphologic and immunohistochemical study

Partial atrophy is the most common benign mimicker of prostate cancer on needle biopsy. Of 3916 prostate needle core biopsy cases received in our consultation service over a period of 3 months (March 1, 2007 to May 31, 2007), 170 cases (4.3%) with partial atrophy were diagnosed as atypical glands by outside pathologists and prospectively identified. We supplemented our material with 108 cases of partial atrophy sent to our consultation service in 2006 from a single institution, which frequently uses a triple cocktail stain [p63, high molecular weight cytokeratin (HMWCK), alpha-methyl acyl-Coa racemase (AMACR)]. The morphologic features of the 278 cases and immunohistochemistry of 236 cases (198 with prostate cocktail and 38 with only basal cell makers) were analyzed. Forty-eight of 278 (17.3%) partial atrophy cases were mixed with postatrophic hyperplasia. Enlarged nuclei were visible in 43/278 (15.5%) cases, with prominent nucleoli seen in 58/278 (20.9%) cases (30 cases associated with nuclear enlargement). Of 198 cases with a prostatic cocktail stain, 48 (24.2%) had a cancer pattern for both basal cells and AMACR (p63-, HMWCK-, and AMACR+), 14 (7.1%) had a cancer pattern for basal cells (p63-, HMWCK-, and AMACR-), 89 (44.9%) had a cancer pattern for AMACR (p63+, HMWCK+, and AMACR+), and 47 (23.7%) had a totally benign pattern (p63+, HMWCK+, and AMACR-). Of the 198 cases using the cocktail stain, 136 (68.7%) had positive basal cell staining. The percentage of basal cells labeled with the combination of p63/HMWCK was: <5% in 42 (21.2%) cases, 5% to 75% in 58 (29.3%) cases, and >75% in 36 (18.2%) cases. An additional 38 cases immunostained only for p63 and/or HMWCK was negative in 2 (5.2%) cases, <5% (13.1%) in 5 cases, 5% to 75% in 19 (50%) cases, and >75% in 12 (31.6%) cases. In conclusion, partial atrophy is a benign mimicker of adenocarcinoma both as a result of its routine morphologic features and its immunohistochemical profile. Recognition of the classic morphology of partial atrophy on routine hematoxylin and eosin-stained sections is critical to avoid misdiagnosing partial atrophy as adenocarcinoma.     

Small glandular proliferations on needle biopsies: most common benign mimickers of prostatic adenocarcinoma sent in for expert second opinion

The current study aimed to determine the incidence of various benign mimickers of prostatic adenocarcinoma most commonly encountered in a busy consultation practice. All prostate needle biopsies from the consult service of one of the authors were prospectively evaluated over a 7-month period. Only cases with foci where the contributor questioned malignancy and which upon expert review the entire case was determined to be benign were included in this study. A total of 567 separate suspected atypical foci from 345 patients of a total of 4,046 patients (8.5%) received in consultation were identified. Of these, 281 foci (49.5%) had immunohistochemical (IHC) studies performed by the outside institution, which included high molecular weight cytokeratin (HMWCK) (n = 280), alpha-methylacyl-CoA racemase (AMACR) (P504s) (n = 45), and p63 (n = 34). The most common mimicker was partial atrophy (203 of 567; 35.8%). Technically adequate IHC for basal cells was performed in 117 cases of partial atrophy with patchy or patchy/negative staining seen in 102 of 117 (87%), with the remaining 13% of cases completely negative. A total of 15 of 19 (79%) cases of partial atrophy were positive with AMACR. Crowded benign glands, insufficiently crowded or numerous to warrant a diagnosis of adenosis, was the second most common mimicker (146 of 567; 25.7%). Crowded benign glands had patchy or patchy/negative IHC for basal cells in 66 of 81 (81%) cases with the remaining 19% of cases completely negative. A total of 7 of 11 (64%) cases of crowded glands were positive for AMACR. In the past, complete atrophy, adenosis, seminal vesicle, and granulomatous prostatitis were considered common mimickers of prostate cancer on prostatic needle biopsies. Our study shows that currently partial atrophy and crowded benign glands are the most common benign changes causing diagnostic difficulty and prompting consultation. Negative or patchy staining for basal cells and positive staining for AMACR may contribute to diagnostic difficulty in these entities.     

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (相似文献   

False positive labeling of prostate cancer with high molecular weight cytokeratin: p63 a more specific immunomarker for basal cells

Occasional nonspecific staining of prostate cancer cells with high molecular weight cytokeratin (HMWCK) can lead to false-negative diagnoses. We compared p63 and HMWCK immunostaining to check their specificity for basal cell identification. Out of 6887 prostate cancer cases sent in consultation to one of the authors over 1.5 years, we identified 22 (0.3%) cases with HMWCK labeling of cancer cells, including 20 needle biopsies and 2 transurethral resections of prostate (TURP). Cases were sent in consultation because of the confusing immunostaining pattern, where prostate cancer cells labeled with HMWCK at the outside institutions. In 6 cases, p63 immunostains were also received from the outside institution, whereas in the remaining 16 cases p63 immunohistochemistry was performed at our institution. In 14 cases, we used either an extra destained hematoxylin and eosin slide or a negative control slide for immunohistochemistry with antibodies to p63, and in the 2 remaining cases submitted unstained slides were used. The Gleason scores were 3+3=6 in 20 cases and 4+4=8 in 2 cases. The size of the tumor on needle biopsy ranged from 0.5 to 6.0 mm (mean 1 mm) and on the 2 TURP cases consisted of 44 and 68 cancer glands, respectively. The number of tumor cells positive for HMWCK in each of the needle biopsy cases ranged from 3 to 48 (mean 13 cells), whereas on the 2 TURP cases 26 and 10 cells were labeled with HMWCK. Corresponding stains for p63 on the same cases were negative in 18 cases. In 3 of 4 cases, p63 labeled 1, 1, and 2 tumor cells, respectively. The fourth case had 5 positive cells on p63 staining with 4 positive for HMWCK. To assess whether overstaining was a factor, we evaluated the intensity of HMWCK staining in the basal cells of the benign glands, which was moderate in 6 and strong in 16 cases. The cytoplasm of benign secretory cells showed focal weak (n=3), diffuse weak (n=1), and focal moderate (n=2) staining for HMWCK. HMWCK labeling of prostate cancer cells is uncommon and does not seem to be solely attributable to overstaining. p63 is a more specific marker for basal cells than HMWCK, with less labeling of tumor cells. Recognition of this phenomenon and performing stains for p63 when it occurs can help prevent underdiagnosing prostatic carcinoma.     

Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma

Objective

In this study, we aimed to investigate which basal cell marker should be used with α-methylacyl coenzyme A racemase (AMACR) to increase diagnostic accuracy in the diagnosis of prostate carcinoma.

Materials and methods

A total of 98 cases of prostate biopsy, comprising 65 cases with prostate adenocarcinoma and 33 cases without adenocarcinoma, were included in this study. Prostate-specific antigen (PSA) serum levels before biopsies were obtained. The number of cores with malignant glands and Gleason scores for each case were determined. Paraffin sections were stained immunohistochemically with 34βE12, keratin 5/6, p63, bcl-2, and AMACR.

Results

According to staining pattern, extensiveness, and intensity of basal cell markers in benign glands, 34βE12 gave the best results. As negative markers for prostate adenocarcinoma, the best markers were p63 and 34βE12. According to the AUC values in ROC curves for both extensiveness and intensity, the arrangement from the best to the worst was 34βE12, p63, bcl-2, and keratin 5/6. The 34βE12 had the best sensitivity and specificity values (95% and 98%, respectively). Staining extensiveness and intensity of keratin 5/6 in malignant glands, and those of bcl-2 in benign glands had statistically significant positive correlation with serum PSA levels. Even though AMACR is a negative marker for benignity, some of the benign glands also had positive immune reaction with AMACR. However, AMACR positivity was usually focal and weak. Nevertheless, intensively stained subjects were also present. No correlation was present between AMACR and basal cell markers.

Conclusions

As a result, we suggest that keratin 5/6 and bcl-2 should not be used to identify benign glands in prostate biopsy since they show high positivity in malignant glands and high negativity in benign glands. 34βE12 should be the first choice as a basal cell marker. p63 can be used together with 34βE12, but it may not give additional diagnostic information. When we evaluated the correlation of basal cell markers, we did not find any complementary staining results among basal cell markers. Our study showed that 34βE12 is the most appropriate negative marker to combine with AMACR as a positive marker for the diagnosis of prostate adenocarcinoma.     

Rare and unusual histological variants of prostatic carcinoma: clinical significance

We review the clinicopathological features of the following unusual histological variants of prostatic carcinoma: small cell carcinoma, ductal adenocarcinoma, sarcomatoid (carcinosarcoma), basal cell, squamous cell and adenosquamous, and urothelial carcinoma. These variants are rare and account for 5-10% of carcinomas that originate in the prostate. Some develop from acinar adenocarcinoma after hormonal or radiation therapy. They are usually aggressive tumours that often present with secondary deposits. The outcome is generally poor. Only basal cell carcinoma is seen as a low-grade carcinoma.     

Carcinoma of prostatic ducts.

Carcinoma of prostatic ducts is a rare clinical feature. We have reviewed 398 histories of patients with histologic diagnosis of prostatic carcinoma and found 10 patients with the ductal variety (2.51%). Four had pure ductal transitional cell carcinoma, 5 had mixed acinar adenocarcinoma plus ductal transitional cell carcinoma, and the last one had mixed acinar and ductal adenocarcinoma. Age, symptoms, physical findings, and imaging diagnoses were similar to those of acinar carcinoma. Rectal examination disclosed hard prostate in 9 patients. The metastatic way depended on the histologic elements present in each patient. Cystoscopy showed a malignant-resembling image in 4 cases. The mean survival (23 months) was lower than that of patients with acinar carcinoma. Early diagnosis and radical surgery still are the only way to increase the expectation of life of patients affected by this pathology.     

Variants and Unusual Patterns of Prostate Cancer

Beyond the typical acinar morphology observed in most prostatic adenocarcinoma, a spectrum of morphologic variants and prostate cancer subtypes exists. These unusual entities may be further classified into (1) cancer morphologies arising by divergent differentiation of prostatic ductal, acinar, or basal cells and associated with unique clinical features or therapeutic approaches, and (2) histologies occurring in the context of usual prostatic adenocarcinoma that may result in diagnostic misinterpretation or difficulties in Gleason grade assignment, especially in limited samples. This article details several variants, with emphasis on diagnostic criteria, differential diagnoses, and clinical significance.     

AMACR(P504S)、P63、34βE12联合检测在前列腺癌早期诊断中的应用

目的:探讨AMACR(P504S)、P63、34βE12联合检测在前列腺癌(PCa)早期诊断中的临床应用价值。方法:应用即用型组合式单克隆抗体和双酶标记的免疫组化MaxvisionTM一步法检测42例PCa、12例高级别前列腺上皮内瘤变(HGPIN)和30例良性前列腺增生(BPH)穿刺活检标本中AMACR、P63、34βE12的表达情况。比较Glea-son评分各组中AMACR阳性表达情况。结果:AMACR、P63、34βE12抗原在PCa和BPH穿刺标本中的表达差异均有极显著性(P<0.01),PCa组织中AMACR阳性表达率为100%,无P63和34βE12表达;BPH组织中均无AM-ACR表达,P63和34βE12均高表达。HGPIN中AMACR的阳性表达率(91.67%)与BPH差异有极显著性(P<0.01),与PCa差异无显著性(P>0.05);P63和34βE12阳性表达率HGPIN(100%)与PCa差异有极显著性(P<0.01),而与BPH差异无显著性(P>0.05)。AMACR表达强弱与PCa的Gleason评分无关(P>0.05)。结论:AMACR是PCa高度敏感和特异的标志物,P63和34βE12联合标记基底细胞的特异性高,3者联合检测能增加前列腺穿刺活检标本诊断的准确性,在PCa早期诊断中具有重要的临床应用价值。     

Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma

Alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a useful marker for the diagnosis of prostatic adenocarcinoma and a potential aid in its distinction from its many mimics, one of which is the benign lesion, nephrogenic adenoma (NA). The goal of this study was to assess the expression of AMACR in NA by immunohistochemistry, as well as other potentially useful markers, high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases showed circumferential granular cytoplasmic AMACR expression of at least moderate intensity, in >75% of tubules in 3 cases and in <10% of tubules in the remaining case. The AMACR-positive cases in the bladder typically showed focal weak noncircumferential staining of the tubules and stronger staining of the cells lining the papillae. 34betaE12 staining was observed in 1/4 prostatic NAs and 4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63 and PSA were negative in all cases. Our data indicate that NA of the prostatic urethra commonly expresses AMACR and lacks basal cell-specific markers, making it not only a potential morphologic mimic of prostatic adenocarcinoma but also a significant immunohistochemical mimic as well. Awareness of NA as a significant pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of hematoxylin and eosin-stained sections remains the key to the correct diagnosis, which can be supported by a negative PSA stain.     

Age-associated changes in alpha-methyl CoA racemase (AMACR) expression in nonneoplastic prostatic tissues

Alpha-methyl CoA racemase (AMACR) is overexpressed in several human cancers, most notably colon and prostate. AMACR expression in the prostate has been investigated primarily in patients, in an older age group, treated for prostatic carcinoma and benign prostatic hypertrophy. No studies have assessed the age distribution of AMACR expression in normal men. Archival paraffin-embedded prostate tissue from 41 organ donor men (age range, 13-63 years) with no evidence of prostate neoplasia was stained with a monoclonal antibody for AMACR. Intensity was graded on a scale of 0 to 3. Semi-quantitative analysis of staining in acinar cells was used to generate a composite score (CS) [Sigma(% area x intensity)] for each case. Nondonor cases with foci of prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN) were used as external positive controls for AMACR. These sections were also stained for Ki-67, to assess proliferative index. The 41 cases encompassed different age groups (13-20 years, N = 11; 20-45 years, N = 17; >45 years, N = 13). Acinar cells showed granular cytoplasmic staining. Focal positive staining was also seen in the prostatic urethra and the periurethral glands. There was wide variation in the level of expression within each age group. The level of expression seen in subjects younger than 45 years was higher (mean CS = 41.3; median CS = 22.5) than that seen in subjects older than 45 years (mean CS = 8.8; median CS = 9.0) with a P value of 0.01. Most cases in the control set of prostatic adenocarcinoma cases showed moderate to strong staining. A negative correlation was seen evaluating CS and age in subjects 20 years of age and older (r = -0.47). Ki-67 staining was variable. 1) AMACR expression can be seen in benign prostatic glandular epithelium, across all age groups. However, it is age-related, with significantly lower expression in subjects younger than 45 years. This could account for the negative staining reported in benign glands, due to biased sampling of the older population. 2) Focal positive staining is seen in the prostatic urethra and periurethral glands in 71% of the cases, with no age correlation. This is of concern because this epithelium could potentially be misinterpreted as foci of PIN. 3) The low expression of AMACR in benign glands in the older age group makes this marker useful in detecting malignancy. However, AMACR staining should be interpreted with caution and the diagnosis of PIN or prostate cancer should be rendered only with convincing histologic evidence. 4) Ki-67 staining was very variable and showed no correlation with age and AMACR expression levels. AMACR expression had no correlation with proliferative index.     

A case of prostatic duct adenocarcinoma: its clinical significance in comparison with typical acinar adenocarcinoma

We report a case of prostatic duct adenocarcinoma treated with radical prostatectomy. Advanced pathological stage (pT3bpN1) was beyond the prediction of the favorable preoperative parameters (cT1cN0, PSA 7.64 ng/ml). The main tumor of ductal adenocarcinoma was occupying the transitional zone and surrounded by scattered micro-foci of acinar adenocarcinoma. We identified coexistence of ductal and acinar adenocarcinoma cells side by side in the same gland. Pure ductal cancer cells were detected in the metastasized lymph node without acinar cancer cells. Strong staining of PSA and loss of p63 expression by both types of adenocarcinoma cells were confirmed immunohistochemically. We discuss the clinical significance of prostatic duct adenocarcinoma in comparision with typical acinar adenocarcinoma.     

α-甲酰基辅酶A消旋酶和雄激素受体在前列腺癌中的表达及其意义

目的 探讨α-甲酰基辅酶A消旋酶(AMACR)和雄激素受体(AR)在前列腺癌中表达的临床病理学意义,并对中日两组前列腺癌患者进行对比分析.方法 采用组织病理学方法 对113例前列腺癌进行复查并对其中101例腺泡癌进行分级,免疫组织化学方法 观察103例前列腺腺泡癌AMACR和AR的表达情况.肿瘤细胞胞质中出现棕黄色细颗粒为AMACR阳性,细胞核中出现棕黄色颗粒为AR染色阳性.结果 中国人组83例中腺泡癌73例,尿路上皮癌4例,神经内分泌癌6例.除2例因组织太少不宜分级外,71例腺泡癌中Gleason评分小于7分3例;7分10例;大于7分58例.日本人组30例前列腺癌均为前列腺腺泡癌.Gleason评分小于7分16例,7分12例,8分2例.中国人组73例中AMACR阳性表达率为63.01%(46/73),日本人组为96.67%(29/30),中日两组的表达水平差异有统计学意义(χ~2=12.160,P＜0.01).中国人前列腺癌三组评分与AMACR阳性表达率差异无统计学意义(χ~2s=2.035,P＞0.05).中日两组前列腺癌组织中AR的阳性表达率分别为39.73%(29/73)和80.00%(24/30),两组阳性表达率差异有统计学意义(χ~2=13.807,P＜0.01).中国人前列腺癌三组评分与AR阳性表达率差异无统计学意义(χ~2=2.079,P＞0.05).结论 AMACR、AR的表达可对前列腺癌的诊断与鉴别诊断提供参考,也是患者预后判定的依据之一;中、日两国前列腺癌的生物学行为存在着差异,中国人组分化差、恶性程度高、预后不良.     

Sarcomatoid carcinoma of the prostate: a study of 42 cases

Sarcomatoid carcinoma of the prostate is a rare type of prostatic cancer. With the exception of 1 study, the morphologic features and patient outcomes have been reported only in relatively small case series and individual reports. We examined transurethral resection, needle biopsy, and radical prostatectomy specimens from 42 patients with sarcomatoid carcinoma of the prostate, all of which were received in consultation. Clinical information on 32 patients was obtainable. Five patients were lost to follow-up and information on the 5 remaining patients could not be obtained. Prior prostatic adenocarcinoma: The majority of patients (n=21; 66%) had a prior history of acinar adenocarcinoma of the prostate. Of the 14 men with available data, reported Gleason scores were 6 (n=7), 8 (n=4), and 10 (n=3). Of the remaining patients for whom this information was known, 11 patients presented with de novo sarcomatoid carcinoma. The time between the original diagnosis of acinar adenocarcinoma and diagnosis of sarcomatoid carcinoma ranged from 6 months to 16 years (mean 6.8 y). Concurrent adenocarcinoma: The majority of patients demonstrated a concurrent high grade acinar carcinoma of Gleason score 7 (n=3), 8 (n=9), 9 (n=10), and 10 (n=10). A subset of patients contained an admixed ductal adenocarcinoma (n=4), small cell carcinoma (n=3), squamous cell carcinoma (n=3), or other unusual pattern of prostate carcinoma (n=3). In 1 case, the diagnosis was based on immunohistochemical evidence of epithelial differentiation along with the history of prior adenocarcinoma. Morphology of the sarcomatoid component: The percentage of sarcomatoid growth ranged from 5% to 99% (mean 65%). Bizarre atypia with giant cells was present in 55% of cases. Admixed heterologous elements were identified in 10 cases (29%), including osteosarcomatous (n=7), chondrosarcomatous (n=5), and rhabdomyosarcomatous (n=2) elements. Of the 12 cases with received immunostains of the sarcomatoid component, 5/7 cases were at least focally positive for cytokeratin, 1/1 case was focally positive for Cam5.2, and 3/6 cases were focally positive for prostate acid phosphatase. The sarcomatoid component did not demonstrate immunoreactivity for prostate-specific antigen in 8 cases. Prognosis: approximately half of all patients developed metastatic disease either at time of presentation or subsequently. Of patients with meaningful follow-up, 6/7 died within 1 year of the diagnosis of sarcomatoid carcinoma; 20 were alive yet with very short follow-up (median 1 y; mean 2.3 y). Kaplan-Meier analysis revealed that the actuarial risk of death at 1 year after diagnosis of sarcomatoid carcinoma was 20%. No correlation was identified between patient survival and morphologic features, before radiation or hormone therapy, or concurrent high-grade prostate cancer. Sarcomatoid carcinoma demonstrates diverse spindle and epithelial cell morphologies. The sarcomatoid component often has heterologous elements and, in 1 case, no epithelial component was seen on hematoxylin and eosin-stained sections. The epithelial component is typically high-grade acinar adenocarcinoma, yet other aggressive tumor subtypes such as ductal adenocarcinoma and small cell carcinoma may also be seen. Sarcomatoid carcinoma is an aggressive form of prostate cancer, the prognosis of which is dismal regardless of other histologic or clinical findings.     

Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma

BACKGROUND: The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. METHODS: Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. RESULTS: We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests that androgens may not be required for the initiation or progression of these cancers. CONCLUSIONS: Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard, the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally, we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together, these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development.     

Role of canine basal cells in prostatic post natal development, induction of hyperplasia, sex hormone-stimulated growth; and the ductal origin of carcinoma

BACKGROUND: The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men it appears to be rare in dogs and unlike the disease in humans it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. METHODS: Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from 19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5 alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5 alpha-androstane-3 alpha diol and estradiol-17 alpha as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), Pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. RESULTS: We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed KI-67. In contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The numbers of HMC and KI-67-stained acinar basal cells were dramatically increased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic carcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR which suggests that androgens may not be required for the initiation or progression of these cancers. CONCLUSIONS: Our findings indicate that two biologically distinct populations of basal cells may exist in the canine prostate. In this regard the age-related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine prostatic hyperplasia. Additionally we find that prostatic carcinoma in the dog likely arises from ductal cells. Taken together these findings may indicate that canine acinar basal cells and ductal epithelium have separate susceptibilities to factors that promote hyperplastic or neoplastic development. Prostate 47:149-163, 2001.     

Expression of alpha-methylacyl-coenzyme A racemase in nephrogenic adenoma

Nephrogenic adenoma is a benign lesion composed of small glandular structures that develops along the urothelium with uncertain pathogenesis. Some investigators believe that nephrogenic adenoma develops by a metaplastic process in response to injury to the urothelium, while others believe that it arises from detached renal tubules. Nephrogenic adenoma may be present in the prostatic urethra and morphologically mimic prostatic adenocarcinoma. Alpha-methylacyl-coenzyme A racemase (AMACR), a recently identified prostate cancer marker, is typically negative in normal urothelium and prostatic glands, and positive in distal convoluted renal tubules in addition to prostatic adenocarcinomas. Therefore, evaluation of AMACR expression in nephrogenic adenoma will have significance in the pathologic diagnosis and in understanding pathogenesis of this lesion. We studied 38 nephrogenic adenomas by clinical, histologic, and immunohistochemical analyses for AMACR (P504S) and high molecular weight cytokeratin (34betaE12). Twenty-two of 38 nephrogenic adenomas (58%) demonstrated strong cytoplasmic positivity for AMACR, ranging from patchy, focal to diffuse staining. In addition, 16 of 26 (62%) nephrogenic adenomas were negative for 34betaE12. To our knowledge, this is one of the first report of a completely benign lesion, which can be found in the prostate, showing strong AMACR immunoreactivity. Our findings suggest using caution when interpreting positive AMACR immunostaining in prostatic specimens. These findings could be explained by possible renal tubular origin or renal differentiation, at least in a subset, of nephrogenic adenomas.