The utility of Ki-67 expression in the differential diagnosis of prostatic intraepithelial neoplasia and ductal adenocarcinoma

Cribriform and/or papillary prostatic lesions observed on limited tissue, such as needle biopsy, can pose diagnostic dilemmas. One such area of difficulty is the distinction between papillary and/or cribriform prostatic high-grade prostatic intraepithelial neoplasia (HG-PIN) and ductal adenocarcinoma. Over 48 months, we identified 17 cases of ductal adenocarcinoma and 17 cases of HG-PIN from radical retropubic prostatectomy specimens. The HG-PIN lesions were in all cases associated with an acinar prostatic adenocarcinoma component. For each case, we evaluated the proliferative activity, assessed by Ki-67 immunohistochemistry. The majority (82%) of ductal adenocarcinomas were composed of mixed papillary and cribriform patterns, with the remaining demonstrating pure papillary or cribriform patterns. The HG-PIN lesions showed a papillary, cribriform, or mixed papillary/cribriform architecture. The proliferative activity, defined as Ki-67 labeling index, was statistically higher in ductal adenocarcinoma (mean 33%, range 21%-66%) as compared with HG-PIN (mean 6%, range 2%-15%), with no overlap in the Ki-67 indices (P = 0001). A combination of histological features and measurements of cellular proliferation may be helpful to distinguish HG-PIN from ductal adenocarcinoma in limited prostatic tissue samples.     

尿道前列腺型息肉1例并文献复习

目的:探讨尿道前列腺型息肉的临床病理学特点、诊断及鉴别诊断.方法:收集天津市武清区人民医院诊治的尿道前列腺型息肉l例,收集患者详细的临床资料、实验室检查、病理检查资料、患者的治疗及随访情况,结合文献进行分析.结果:患者,33岁,男性,右侧腰腹部间断疼痛2年.泌尿系超声检查示:右肾盂积水,右输尿管结石.经输尿管钬激光碎石术中发现尿道前列腺部有直径5 mm的息肉一枚.镜下可见肿物被覆两种上皮,为无异型的前列腺型上皮和移行上皮.腺上皮形成腺泡状和乳头状结构,细胞排列为两层.免疫组织化学示基底层细胞胞核表达p63,分泌层细胞胞浆表达PSA,两种细胞均未表达P504s和Ki-67.结合病史、辅助检查及病理组织学,最终诊断为尿道前列腺型息肉.患者经碎石及息肉切除后痊愈,随访2年无复发.结论:尿道前列腺型息肉少见,正确诊断对治疗有重要指导意义.组织学形态需注意与表现为尿道息肉的前列腺导管腺癌等鉴别.诊断需结合病史、临床症状、内镜下表现、组织学及免疫组织化学检查等综合分析.     

Urinary cytologic findings in patients with benign and malignant adenomatous polyps of the prostatic urethra

CONTEXT: Urethral adenomatous polyps with prostatic epithelium (also known as benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria, dysuria, and hematospermia, conditions that may prompt cytologic evaluation of urine. DESIGN: The urine cytologic test findings in 5 cases of biopsy-proven BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a urethral polyp were retrospectively evaluated. Immunocytochemical stain for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high-molecular-weight cytokeratin (34betaE12) were used in evaluation of the lesions. RESULTS: In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform, oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the prostatic origin of the clusters in 2 cases. One urine sample contained abundant goblet cells and extracellular mucin, consistent with intestinal metaplasia coexisting in the bladder biopsy specimen. The urine sample in the fifth case of BPEPs contained no columnar cells. The last case had multiple urine cytologic evaluations that demonstrated PSA-positive, malignant-appearing clusters of columnar cells. A biopsy specimen of the polyps was described as a high-grade prostatic intraepithelial neoplasm in adenomatous polyp. However, in this patient, PDA was diagnosed on transurethral resection of the prostate specimen 4 years after the initial urine cytologic test. CONCLUSION: Benign prostatic epithelial polyps should be considered in the differential diagnosis of clusters of columnar cells in urine cytologic testing. Cells with malignant nuclear features should instigate a careful search for a (prostatic) neoplasm, which may present as urethral polyps (e.g., PDA). Stains for PSA or PAP are useful adjuncts in differential diagnosis of this condition.     

Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia

Reactive urothelial atypia (RUA) can be difficult to differentiate from dysplastic urothelium. The goal was to evaluate the efficacy of cytokeratin 20 (CK20), Ki-67 and E-cadherin (E-Cad) in this regard. Fifty carcinoma in situ (CIS) cases, 50 non-neoplastic urothelia (25 normal, 25 reactive urothelial atypia (RUA)) and 17 atypia of unknown significance (AUS) cases were evaluated. All cases were stained with monoclonal antibodies against Ki-67, CK20 and E-Cad. All (100%) normal urothelia showed normal staining patterns. In the CIS group, 86%, 82% and 20% of cases showed abnormal expression with CK20, Ki-67 and E-Cad, respectively. Both Ki-67 and CK20 were positive in 68% of cases. In the RUA group, 96%, 72% and 100% of cases showed normal expression patterns with CK20, Ki-67 and E-Cad, respectively. Of 28% RUA cases with increased Ki-67, none demonstrated abnormal CK20 or E-Cad expression. In the AUS group, 47% demonstrated abnormal CK20 and increased Ki-67 expression, suggestive of urothelial dysplasia/CIS, 29% were negative with both, suggestive of RUA, and the remaining 24% cases could not be resolved. In summary, abnormal CK20 is a useful adjunct to morphology for confirming dysplasia. Ki-67 by itself is a less reliable marker of dysplasia. E-Cad is not a useful marker in this setting.     

Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.     

抗体鸡尾酒AMACR/P63/34βE12在前列腺良恶性病变鉴别诊断中的应用价值

目的:探讨抗体鸡尾酒AMACR/P63/34βE12在前列腺良恶性病变鉴别诊断中的应用价值。方法:收集2001~2005年111例前列腺手术切除标本，其中前列腺腺癌39例，高级别前列腺上皮内瘤（high-grade prostatic intraepithelial neoplasias，HGPIN）29例，非典型性腺瘤样增生（atypical adenomatous hyperplasia, AAH）3例，前列腺结节性增生（benign prostatic hyperplasia, BPH）40例。作抗体鸡尾酒AMACR/P63/34βE12的免疫标记，观察3种抗体在各类病变中的表达情况。结果:39例前列腺腺癌AMACR全部呈阳性，癌巢周围无基底细胞残存（P63/34βE12阴性）。29例高级别前列腺上皮内瘤变，14例（48.3%）腺泡上皮AMACR呈阳性，29例腺泡上皮周围有连续或不连续的基底细胞（P63/34βE12阳性）。3例非典型性腺瘤样增生中2例腺泡上皮AMACR呈弱阳性；3例腺泡上皮周围有较连续的基底细胞（P63/34βE12中度阳性）。40例前列腺结节性增生，腺泡上皮AMACR染色均呈阴性，周围有连续的基底细胞（P63/34βE12强阳性）。结论:鸡尾酒抗体AMACR/P63/34βE12标记前列腺组织，能够同时高特异性和敏感性地检测出前列腺腺癌细胞（或非典型增生的腺泡上皮细胞）和基底细胞，为前列腺腺癌与高级别上皮內瘤变、非典型性腺瘤样增生、前列腺结节性增生的鉴别诊断提供有力的证据。     

Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker

AIM: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. METHODS AND RESULTS: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). CONCLUSIONS: We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.     

结直肠锯齿状病变104例形态学及细胞增殖活性的观察

目的 探讨结直肠锯齿状病变增生性息肉(HP)、广基锯齿状腺瘤(SSA)、传统锯齿状腺瘤(TSA)的临床特征,组织病理学诊断,鉴别诊断及细胞增殖状况.方法 复习北京军区总医院2002年11月至2007年12月2628例病理诊断为结直肠息肉/腺瘤的病理切片,从中收集104例结直肠锯齿状病变,综合文献标准进行分类,观察各类型病变临床病理学特征,以及细胞增殖指数Ki-67的表达特点.结果 104例锯齿状病变中包括HP 60例,TSA 20例,SSA 11例,混合性锯齿状息肉/腺瘤7例,混合件锯齿状息肉/腺瘤+普通腺瘤6例.对各型组织学特征进行总结归纳.免疫组织化学显示正常结肠黏膜Ki-67阳性细胞位于基底(隐窝下1/3),呈间隔分布;51例HP中阴性或阳性细胞数最<25%的40例(78%),大多数阳性位于隐窝下1/3(基底);15例TSA中11例阳性细胞数量在25%～50%或>50%,其中大多数位于隐窝中1/3,少数(2例)隐窝弥漫分布;SSA的数量与分布和TSA相似;相比之下低级别管状腺瘤26例中24例(92%)阳性数量>50%,18例(69%)分布于隐窝表面,6例(23%)弥漫分布;高分化管状腺癌10例全部呈弥漫分布,7例Ki-67阳性指数在70%左右.阳性细胞多少与分布部位差异有统计学意义,阳性细胞)χ2=34.601,P=0.000,阳性分布χ2=63.077,P=0.000.结论 HP、SSA、TSA组织学鉴别诊断的主要难点是在HP与SSA两者之间,SSA锯齿状隐窝基底扩张结构特征是诊断的关键,比细胞学改变更重要.TSA与SSA的主要形态鉴别在于TSA锯齿状腺体有明显异型增生(普通腺瘤样增生)以及几乎所有TSA异型增生的腺体都不与黏膜肌相邻(ECF现象).细胞增殖指数Ki-67数量及分布的表达可为HP、SSA及TSA鉴别诊断提供一定帮助.锯齿状腺瘤中TSA和SSA的Ki-67表达指数都比普通腺瘤要低.     

Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia

Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89?%) endometrial polyps, but in only 1 (3?%) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90?% (mean, 47?%) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94?%) and hyperplasia 27 (82?%). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.     

Villous adenoma of the urinary tract; a clinicopathological study北大核心CSCD

Objective: To explore the clinicopathological features, immunophenotype, differential diagnosis, pathogenesis and prognosis of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract. Methods: Clinical and pathologic findings of 3 cases of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract were analyzed by gross examination, microscopic investigation and immunohistochemical staining. The related literatures were reviewed. Results: All of the three cases were middle-aged or elderly patients. Three cases all presented with hematuria and mucusuria. Endoscopic examination identified that case 1 had a polyp with broad attachment in the dome of bladder, case 2 had a solid mass in the ureter, and case 3 had a exophytic fungating tumor in the renal pelvis. Microscopically, case 1 revealed a papillary lesion with finger-like processes lined by pseudostratified columnar epithelium with abundant goblet cells. The cells demonstrated moderate degree dysplasia. In case 2 and case 3, both villous adenomas and poorly differentiated adenocarcinoma were observed, the adenoma cells arranged in a cribriform pattern, and the tumor cells showed severe atypia, mitotic activity, and transition with invasive poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells in three cases were positive for CK20,CEA,EMA and MUC-1; none of them expressed cdx-2 and PSA; In case 2 and 3, the same immunophenotype of villous adenomas and their associated adenocarcinomas was observed, but the number of the positive cells of p53 and Ki-67 staining were significantly increased in the area of adenocarcinomas than in that of the villous adenomas. Conclusions: Villous adenoma of the urinary tract is rare. It can occur in the urinary bladder, urachus, renal pelvis, ureter and urethra. These lesions may have malignant potential and frequently coexist with other malignant tumors. So, villous adenoma of the urinary tract should be removed completely and sampled thoroughly to avoid missing a more aggressive component.     

Clear cell adenocarcinoma present exclusively within endometrial polyp: report of two cases

Endometrial polyp is a common benign lesion that protrudes into the endometrial surface. The incidence of carcinoma within endometrial polyp is thought to be low, however, postmenopausal women with endometrial polyps are at an increased risk. Endometrial clear cell adenocarcinoma is a distinct and relatively rare subtype of endometrial carcinoma, and recent studies have proposed putative precursor lesions of clear cell adenocarcinoma, namely clear cell endometrial glandular dysplasia (EmGD) and clear cell endometrial intraepithelial carcinoma (EIC). Herein, we describe two cases of clear cell adenocarcinoma present exclusively within endometrial polyp and discuss the association of its precursor. Two postmenopausal Japanese females, 66-year-old (Case 1) and 54-year-old (Case 2) presented with abnormal genital bleeding. Cytological examination of both cases revealed adenocarcinoma, thus, hysterectomy was performed. Histopathological studies demonstrated clear cell adenocarcinoma within exclusively endometrial polyp in both cases. The peculiar finding in Case 1 was presence of atypical glandular cells with large round to oval nuclei and clear cytoplasm within the atrophic endometrial glands in the surrounding endometrial tissue, which corresponded to clear cell EIC. A recent study showed that 33% of uteri had at least one focus of clear cell EmGD in endometrial polyps. Accordingly, clear cell adenocarcinoma and clear cell EmGD can occur in association with endometrial polyps more frequently than previously thought. Therefore, detailed histopathological examination is important in diagnosis of endometrial polyps, especially in the postmenopausal women, moreover cytological examination is a useful tool in the postmenopausal women with endometrial polyps.     

Concomitant presence of inflammatory fibroid polyp and carcinoma or adenoma in the stomach

Four instances (8%) of inflammatory fibroid polyp (IFP) with concomitant adenocarcinoma or adenoma, in the same area, were noted among 50 cases of IFP of the stomach. Adding two cases from other sources, four cases of gastric IFP concomitant with an adenocarcinoma and two of gastric IFP concomitant with an adenoma were studied histopathologically and immunohistochemically. All lesions were located in the gastric antrum and they were restricted to the mucosa in three, and they involved both mucosa and submucosa in the other three. Neither S100 protein nor factor VIII-associated antigen was recognized in the principal component cells, using an immunoperoxidase technique. This finding suggests the conventional view that the proliferating cells were neither neurogenic nor angioblastic, but rather, were fibroblastic in origin. The four concomitant carcinomas were early adenocarcinomas restricted to within the mucosa, and the two concomitant adenomas were tubular adenomas with a moderate epithelial atypia. All these neoplasms were present in or adjacent to the IFP. We emphasize that the IFP, albeit benign, may carry an adenocarcinoma or an adenoma.     

Immunohistochemistry in diagnostic surgical pathology of the prostate

Immunohistochemistry (IHC) can play an important role in diagnostic surgical pathology of the prostate. Basal cell markers, such as the 34betaE12 antibody and antibodies directed against cytokeratin 5 and 6 or p63, are very useful for demonstration of basal cells as their presence argues against a diagnosis of invasive prostatic carcinoma (PC). However, several benign mimickers of PC, including atrophy, atypical adenomatous hyperplasia (AAH), nephrogenic adenoma, and mesonephric hyperplasia, can stain negatively with these markers, and thus, a negative basal cell marker immunostain alone does not exclude a diagnosis of benignancy. Although there are examples in the literature of high grade PC that stain focally with some of the basal cell markers, these cases are usually readily diagnosed based on H&E appearances and are unlikely to be confused with these benign mimickers. Alpha-methylacyl-coenzyme-A racemase (AMACR) is a sensitive marker of PC (except for a few uncommon variants: atrophic, foamy gland, and pseudohyperplastic variants), and its detection by immunohistochemical staining in atypical prostatic lesions can be very useful in confirming an impression of adenocarcinoma. AMACR expression can also be identified in high grade prostatic intraepithelial neoplasia (PIN), prostatic atrophy, AAH, and benign prostatic glands, and accordingly, a diagnosis of PC should not be based solely on a positive AMACR immunostain, especially when the luminal staining is weak and/or noncircumferential. The use of AMACR/basal cell antibody cocktails has been found to greatly facilitate the distinction between PC and its benign mimickers, especially when only limited tissue is available for staining. Prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) are both quite sensitive and fairly specific markers of PC (there are a few nonprostatic tumors that can express one or both), and are both very helpful in establishing or confirming the diagnosis of PC when the differential diagnosis includes other tumors that can involve the prostate such as urinary bladder urothelial carcinoma. 34betaE12, p63, thrombomodulin, and uroplakin III are additional urothelial associated markers useful in this differential diagnosis. CDX2 and villin are useful markers to diagnostically separate colonic adenocarcinoma from PC. AMACR positivity and negative basal cell marker reactions are useful to confirm the presence of residual PC after hormonal or radiation therapy. Pan-cytokeratin, PSA, and PSAP can also highlight subtle infiltrates of PC with hormonal or radiation therapy effect. PSA and PSAP immunohistochemical stains are valuable in confirming metastatic carcinoma as being of prostatic origin and should always be utilized in the diagnostic evaluation of metastatic adenocarcinoma of unknown primary origin in males.     

DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer

BACKGROUND: Recent studies have shown that minichromosome maintenance (MCM) proteins (Mcm2-7) may be useful proliferation markers in dysplasia and cancer in various tissues. AIMS: To investigate the use of Mcm7 as a proliferation marker in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly used cell proliferation marker. METHODS: The percentage of proliferating cells (proliferation index; PI) was calculated for basal and luminal epithelial cells in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with the preoperative prostate specific antigen concentration, the Gleason score, surgical resection margin status, and the AJCC pT stage for each patient. RESULTS: The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and 1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and 10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7, respectively. Mcm7 had a significantly higher mean PI (p<0.0001) than Ki-67 for all cell categories except benign luminal epithelial cells. Mcm7 was a better discriminatory marker of proliferation between benign epithelium, PIN, and invasive adenocarcinoma (p<0.0001) than Ki-67. The drop in Mcm7 mean basal cell PI from benign epithelium to PIN epithelium was significantly larger than for Ki-67 (p<0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level. CONCLUSION: Mcm7 may be a useful proliferation marker in prostatic neoplasia and warrants further evaluation as a complementary tool in the diagnosis of PIN and prostate carcinoma.     

假增生型前列腺癌的病理学特征

目的探讨假增生型前列腺癌（PHPA）的临床病理特征及其发生率和生物学行为。方法复查上海交通大学附属第六人民医院2005年1月1日-2006年12月31日860例直肠B超引导下前列腺穿刺活检和46例前列腺癌根治手术切片,对疑有PHPA组织作34βE12（或CK5／6）、p63和AMACR单项免疫组织化学标记（EnVision法）和34βE12／p63／AMACR鸡尾酒抗体双重免疫组织化学标记,将在1个组织块中PHPA占该组织块中癌总量的面积百分比〉60％的病例归入本组,并作病理学分析。结果PHPA在穿刺活检和前列腺癌根治标本中的发生率分别为7．0％和15．2％。66．7％的PHPA与普通型前列腺癌直接移行,76．7％在其他组织块中有普通型癌。PHPA占穿刺活检中癌总量的比例为5％～100％,占根治标本中癌总量的比例为1％～30％。PHPA以大中腺泡增生为主,癌细胞分化较好,排列有极性,腔内常有残存淀粉样小体,低倍镜下类似良性前列腺增生。但腺泡排列紧密,腔内有嗜酸性结晶体和颗粒状无定形物质,核增大,有大核仁,免疫标记AMACR阳性,基底细胞标记阴性,在20项提示恶性的形态学指标中10项出现几率966．7％。PHPA虽然分化较好,但66．7％的PHPA有间质浸润,6．7％有神经浸润,3．3％有腺外浸润,3．3％发生骨转移,肿瘤分布部位周围带多于移行带。结论PHPA的实际发生率不低,绝大多数与普通型癌并存,由于形态学类似良性,肿瘤细胞量又不占多数,因此在诊断中容易被忽视,PHPA高分化前列腺癌不同,应属于Gleason3级的中分化腺癌。     

Differenzialdiagnose des Prostatakarzinoms

Prostate cancer offers a wide range of growth patterns depicted in the classical Gleason diagram. For each Gleason pattern exist a number of benign and malignant mimickers that can simulate prostatic adenocarcinoma. In the present review, the use of immunohistochemical markers is discussed with emphasis to a pattern-based approach to differential diagnosis in prostate pathology. Basal cell markers (34betaE12 and P63) are very useful to analyze histo-architectural features of small and large glandular lesions. AMACR (P504 s) is helpful not only in identifying small amount of cancer in needle biopsies but also in the diagnosis of high grade prostatic intra epithelial neoplasia (HGPIN). A number of lesions which may be confused with small acinar adenocarcinoma (Cowper's gland, nephrogenic metaplasia, mesonephric glands) and poorly differentiated prostate cancer (urothelial neoplasia, mucinous colon cancer and other metastatic lesions) lacks convincing PSA immunoreactivity. Basal cell markers and the nuclear androgen receptors are important markers to differentiate Gleason grade 5 A und 5 B patterns from prostatic involvement by transitional cell carcinoma. Finally, a selected panel of markers is useful to classify prostatic stromal lesions. In each case, immunohistochemical findings should be interpreted in context with the various patterns on routine microscopy.     

Is there a role for fatty acid synthase in the diagnosis of prostatic adenocarcinoma?: A comparison with AMACR

Our aim was to compare the usefulness of fatty acid synthase (FASn) with that of α-methylacyl coenzyme-A racemase (AMACR) in the diagnosis of prostatic adenocarcinoma. The expression of these 2 markers was compared in a tissue microarray containing 62 foci of benign glands and 36 foci of prostatic adenocarcinoma. Similar to AMACR, there was significantly higher FASn expression in adenocarcinoma compared with that in benign glands. The optimal accuracy rate and area under curve (AUC) by receiver operating characteristic analysis for FASn were not significantly different from those for AMACR (accuracy, 80% vs 87%; AUC, 0.942 vs 0.956; P for both, > .05). Moreover, in cases with coexistent malignant and benign glands on the same core, FASn could selectively distinguish a proportion of cases (17/21 [81%]) similar to using AMACR. We conclude that FASn may aid in the diagnosis of prostatic adenocarcinoma, at least to supplement AMACR as another positive marker of carcinoma and potentially increase diagnostic accuracy.     

Immunocytochemical analysis of AE1/AE3, CK 14, Ki-67 and p53 expression in benign, premalignant and malignant oral tissue to establish putative markers for progression of oral carcinoma

Squamous cell carcinoma (SCC) is the most common form of oral malignancy and is often preceded by premalignant lesions, some of which are more likely to progress to carcinoma than others. In this study, a panel of monoclonal antibodies (AE1/AE3, cytokeratin [CK] 14, Ki-67 and p53) is applied to 10 cases of human oral tissue in each of six categories to establish staining patterns indicative of which lesions are more likely to progress to malignancy. The six tissue categories are normal tissue; abnormal benign lesions; mild, moderate and severe dysplasia; and SCC. A statistical analysis of Ki-67 and p53 immunoexpression is performed. The results showed that AE1/AE3 and CK 14 expression was reduced as a late event in oral carcinogenesis, particularly in poorly differentiated SCC. Expression of Ki-67 and p53 proved to be a weak but statistically significant predictor of malignant progression in oral tissue.     

肾源性腺瘤临床病理和免疫组化分析

目的探讨肾源性腺瘤(nephrogenic adenoma,NA)的临床病理表现和免疫组化特征。方法收集5例膀胱和输尿管NA,分析其临床病理和免疫表型特征。结果 3例NA位于膀胱,2例位于输尿管。眼观NA呈乳头状或息肉状,镜下见病变主要由增生上皮细胞形成的小管状、囊状和乳头状结构组成;增生上皮为单层立方状或扁平状,部分呈"鞋钉"样;间质慢性炎。免疫组化染色示增生上皮细胞呈PAX2、CK7、EMA、AMACR/P504S(+),p63、CD10、CD31、PSA(-),Ki-67增殖指数<2%。结论 NA是较少见的瘤样病变,可误诊为其他肿瘤(甚至腺癌)。熟悉其病理学和免疫表型特征是正确诊断的关键。     

Apocrine adenosis: a precursor of aggressive breast cancer?

AIM--To investigate overexpression of c-erbB2, expression of the p53 protein product and proliferation rates in benign breast lesions with specific reference to apocrine adenosis. METHODS--Twenty one cases of apocrine adenosis were stained with monoclonal antibodies to p185, the protein product of the c-erbB2 oncogene, the protein product of the p53 tumour suppressor gene and to the cell cycle related protein Ki67. Three cases were associated with concomitant ductal carcinoma in situ of large cell type and two were associated with invasive tubular or cribriform carcinoma. RESULTS--Twelve (57.1%) cases showed membrane staining for c-erbB2 oncoprotein of apocrine cells within sclerosing adenosis and six (28.6%) had occasional p53 protein positive cells. One case not associated with carcinoma showed extensive staining of apocrine metaplasia outside the area of apocrine adenosis. The proliferation rate, as measured by Ki67 staining, was increased in some of the lesions and all lesions showed at least some of the cells to be in the cell cycle. CONCLUSIONS--The expression of abnormal oncogene products and increased proliferation in some of these apocrine lesions questions the supposed degenerative nature of the atypia seen in such cases and suggests that there may be an association between these lesions and large cell ductal carcinoma in situ and hence invasive carcinoma.