Prospective comparison between serum monoclonal prostate specific antigen and acid phosphatase measurements in metastatic prostatic cancer

Prostate specific antigen, prostatic acid phosphatase antigen and acid phosphatase activity were measured on 175 serum samples serially collected from 80 patients with metastatic stage D adenocarcinoma of the prostate. Prostate specific antigen and prostatic acid phosphatase antigen concentrations were measured with a monoclonal radioimmunometric assay, and acid phosphatase activity was measured enzymatically. The over-all frequency of abnormal levels of prostate specific antigen (76 per cent) was significantly greater than abnormal prostatic acid phosphatase antigen (60 per cent) and acid phosphatase activity (49 per cent) results (p less than 0.001). These differences were greater among the subset of patients in clinical remission. Levels greater than 10 times normal were observed in 68 per cent of prostate specific antigen, 43 per cent of prostatic acid phosphatase antigen and 31 per cent of acid phosphatase activity measurements (p less than 0.001). Three or more serial prostate specific antigen measurements in 17 patients demonstrated excellent correlation with independently assessed clinical disease activity. These results suggest that prostate specific antigen is a more sensitive and potentially more useful tumor marker than acid phosphatase measurements in patients with metastatic prostatic carcinoma.     

Heterogeneous subpopulations of human prostatic adenocarcinoma cells: potential usefulness of P21 protein as a predictor for bone metastasis

Expression of the p21 protein of the ras oncogene family was studied in a case of human prostatic adenocarcinoma tissue and the cell line was derived from the primary tumor. Flow cytometry analysis of the tumor cells obtained from the primary tumor indicated that approximately 25 per cent of the cells were positive for this oncogene product. However, by the immunoperoxidase method almost all of the tumor cells at the vertebral metastatic sites in the same patient were positive for the p21 protein. The cell line established from the primary tumor displayed 2 distinct subpopulation growth patterns in vitro: a monolayer, density-inhibited growth and a multicellular aggregate type growth morphology. These 2 subpopulations could be separated by density elutriation centrifugation. The isolated subpopulation cells were noted to express prostatic acid phosphatase and prostate specific antigen at high frequency. High levels of expression of these 2 prostatic markers also were found in the tumor cells at the vertebral metastatic sites. However, when the isolated subpopulations were analyzed for the expression of p21 protein, the multicellular grown cells were almost 90 per cent positive for the p21 antigen, whereas only approximately 5 per cent of the monolayer grown cells were positive for the same protein. Our findings suggest that primary prostatic carcinomas are composed of heterogeneous subpopulations of neoplastic cells while only specific subpopulations have metastatic potential. Quantification of prostatic acid phosphatase and prostate specific antigen in the primary tumor cells probably will not offer a predictive value for the eventual behavior of the tumors. However, evaluation of oncogene products, such as the p21 protein, may be useful as a clinical predictor for metastatic potential.     

Mucinous adenocarcinoma of prostate: a case report and review of the literature

Mucinous adenocarcinoma of the prostate is rare and its biological behavior is not well known. We report a case of mucinous adenocarcinoma of the prostate, which was treated successfully with castration. Positivity for prostatic specific antigen by immunohistochemistry confirmed the prostatic origin of this tumor. A review of the literature revealed 30 authentic cases. Prostatic mucinous adenocarcinoma has been said to be different clinically from ordinary prostatic adenocarcinoma. It is insensitive to hormonal therapy, rarely produces acid phosphatase and rarely metastasizes to the bone. However, our case, together with the frequent presence of coexisting acinar elements in mucinous adenocarcinoma, indicates no significant difference in the clinical behavior between mucinous and ordinary acinar carcinomas.     

The prognostic significance of tumor-associated markers p53, HER-2/neu, c-myc, v-H-ras, PCNA and EGFr of local and distant recurrence in localized human prostatic adenocarcinoma

The intracellular expression of the gene products of tumor-associated markers p53, proliferative cell nuclear antigen (PCNA), HER-2/neu, c-myc, H-ras, and epidermal growth factor receptor (EGFr) in 86 cases of localized prostatic adenocarcinoma was investigated immunohistochemically in formalin-fixed paraffin-embedded tissue sections after pretreatment with a novel antigen retrieval buffer. A scoring system was devised to assess strength, pattern, and combined strength/pattern of immunostainings in the nucleus and cytoplasm for each immunomarker. The results were evaluated to determine whether overexpression of the gene products in the nucleus and cytoplasm was predictive of local and/or distant tumor recurrence and whether their expression was associated with known clinical prognostic factors. There was no significant relation between p53, PCNA, HER-2/neu, c-myc, and H-ras protein expression with risk of recurrence. EGFr expression showed a trend of increasing risk of tumor recurrence with higher composite score. Analysis of the association with other known prognostic factors in prostatic adenocarcinoma showed that PCNA was significantly correlated with tumor stage while H-ras and HER-2/neu were marginally correlated with prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) pretreatment serum levels, respectively. Together our findings suggest that overexpression of these intracellular oncoproteins in the tumor cells may not play an important role in determining whether prostatic tumors are likely to recur in localized prostatic adenocarcinoma.     

前列腺导管腺癌一例报告并文献复习

目的探讨前列腺导管腺癌的临床、病理特征及治疗方法。方法1例反复血精5个月，血尿4个月的患者直肠指诊示：前列腺右侧可及直径约1cm质软肿物。血清前列腺特异抗原（PSA）0.7ng/ml。前列腺穿刺活检提示前列腺腺癌。患者行根治性前列腺切除术。结果病理报告：前列腺右叶大导管腺癌，向外浸润右侧精囊，Gleason分级5/4（Sum=9），pT3b;免疫组化染色PSA（＋），前列腺酸性磷酸酶（PAP）（＋＋），雄激素受体（AR）（-）。患者术后恢复良好，血精、血尿消失，随访7年仍存活。结论前列腺导管腺癌是前列腺癌罕见的亚型，难于早期诊断，确诊主要依靠病理和免疫组化检查，治疗方法可采用根治性前列腺切除术。     

Breast metastases of prostatic carcinoma: immunohistochemical case study

A breast mass developed in a patient receiving estrogen therapy for prostatic cancer. The prostate tumor was adenocarcinoma of small acinar type, whereas that of the breast was infiltrating medullary adenocarcinoma. Histological features of the two tumors differed and double cancer was suspected by conventional pathological study. However, immunohistochemical staining with prostatic specific antigen and prostatic acid phosphatase was positive in each tumor. These results indicate the breast tumor to be a metastasis from the prostatic cancer.     

Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. I. Untreated patients

Serum prostate specific antigen levels were determined (Yang polyclonal radioimmunoassay) in 230 men with untreated adenocarcinoma of the prostate after careful clinical staging. Prostate specific antigen was directly proportional to advancing clinical stage, statistically failing to distinguish only between consecutive stages B2 and B3, and between stages C and D1. Serum prostatic acid phosphatase by radioimmunoassay was unable to distinguish men with stages C plus D1 from B2 plus B3 disease but it could distinguish stages C plus D1 from A2 plus B1 (p equals 0.015). Serum prostate specific antigen was directly proportional to increasing Gleason score. In 59 untreated patients multiple prostate specific antigen values were obtained during a mean followup of 10 months. Of the patients 81 per cent showed a steady increase with time, including 91 per cent of men with clinical stage B2 or greater disease. The rate of increase accelerated with time, and correlated with advancing tumor stage and increasing serum concentration of prostate specific antigen. The rate of increase of prostate specific antigen in clinical stages A and B cancer patients suggested a doubling time of at least 2 years. Serum prostate specific antigen was significantly decreased by transurethral resection of prostatic tissue in patients with cancer, as has been shown previously in patients with benign prostatic hyperplasia.     

Flow cytometric analysis of comedocarcinoma of the prostate: an uncommon histopathological variant of prostatic adenocarcinoma

Pathological data from 321 patients who underwent radical prostatectomy or cystoprostatectomy with a diagnosis of prostatic adenocarcinoma were reviewed. Of these specimens 4 (1.2 per cent) demonstrated histopathological findings consistent with prostatic comedocarcinoma. Prostatic acid phosphatase and prostate specific antigen detected by immunoperoxidase technique confirmed the prostatic origin of all comedocarcinomas studied. Flow cytometric analysis of deparaffinized sections from these specimens as well as a total of 40 representative specimens from normal prostate, and low, intermediate and high grade prostatic carcinomas was performed. Frequency of aneuploidy in low, intermediate and high grade prostatic adenocarcinoma was 0, 43 and 75 per cent, respectively. All cases of prostatic comedocarcinoma studied had distinctly aneuploid deoxyribonucleic acid histograms and the mean deoxyribonucleic acid content in comedocarcinoma was the highest of all groups analyzed. The mean time to recurrence in patients with comedocarcinoma was 13 months. Our flow cytometric data suggest that prostatic comedocarcinoma represents a potentially aggressive tumor demonstrating cytogenetic aberration shown to be associated with poor clinical outcome in prostatic adenocarcinoma.     

Mucinous adenocarcinoma of the prostate with good response to hormonal therapy: a case report]

A 79-year-old man complained of pollakisuria and sense of retention. The prostate was stony hard and heterogeneously enhanced on computed tomographic (CT) scan. The serum levels of prostatic specific antigen, prostatic acid phosphatase and gamma-Seminoprotein were abnormally high. Prostatic biopsy showed mucinous adenocarcinoma which was stained by prostatic specific antigen. Bone scintigraphy revealed multiple metastases. Hormonal therapy was performed. Each prostatic tumor marker decreased to the normal range within 2 months. After 3 months, the prostate was almost normalized on digital examination and CT scan. There were no new metastases, prostatic biopsy revealed that most cancer cells had degenerated to nonviable cells and bone metastases had decreased.     

Enzyme activity and distribution in rat prostatic adenocarcinoma

The activity and distribution of acid phosphatase, alkaline phosphatase, nonspecific esterases, beta-glucuronidase, and aminopeptidase were examined in the transplantable R-3327 rat prostatic adenocarcinoma and compared with those in the four prostatic lobes of the rat. Both the well and poorly differentiated tumor cells in R-3327 carcinoma were characterized by high activities of beta-glucuronidase and aminopeptidase. The poorly differentiated cells had a high alkaline phosphatase activity. The enzymatic profile of the R-3327 adenocarcinoma closely resembled that of the anterior and dorsal prostate. The origin of the tumor in one of these prostatic lobes is probable, but not certain.     

Pre-treatment and post-treatment evaluation of prostatic adenocarcinoma for prostatic specific acid phosphatase and prostatic specific antigen by immunohistochemistry

Prostatic specific acid phosphatase and prostatic specific antigen have been used as specific markers of prostatic adenocarcinoma in immunohistochemical studies, particularly when seeking the primary site of a poorly differentiated metastasis. We herein evaluate the effect of therapy on the persistence of these markers in surgically obtained tissues. Prostatic biopsies from 30 patients with adenocarcinoma of the prostate gland before and after treatment with orchiectomy alone, diethylstilbestrol, external beam radiation or combined radiation and diethylstilbestrol were studied for prostatic specific acid phosphatase and prostatic specific antigen using the indirect immunoperoxidase technique. The interval between biopsies ranged from 3 to 72 months, with an average of 28 months. All pre-treatment biopsies stained positively for prostatic specific acid phosphatase and prostatic specific antigen. Staining for prostatic specific antigen and prostatic specific acid phosphatase was seen easily in 29 of 30 post-treatment biopsies, while in 1 case infiltrating anaplastic cells surrounded by stroma showed staining for these antigens in an extremely small percentage of cells, which were overlooked easily unless examined carefully. In view of this small number of positively staining cells this case was designated as equivocal. While some cases demonstrated less intense staining in post-treatment biopsies compared to pre-treatment, this finding was by no means constant. With these primary antisera a higher percentage of cytologically malignant cells stained positively for prostatic specific acid phosphatase than for prostatic specific antigen in adjacent tissue sections in some cases. Prostatic specific acid phosphatase and prostatic specific antigen appear to be sensitive and persistent markers of prostatic adenocarcinoma despite morphologic changes accompanying various therapies.     

Urothelial-type adenocarcinoma of the prostate mimicking metastatic colorectal adenocarcinoma

Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.     

Ethnicity and its significance in the pathobiology of prostatic carcinoma in Southern Israel

BACKGROUND: Several studies have noted ethnic differences in the natural history of prostatic carcinoma. Southern Israel has been regarded as a melting pot and, perhaps more than the rest of the country, has encouraged the ingathering of immigrants from several countries, as well as a large Bedouin community. OBJECTIVES: In an attempt to determine any differences that may exist in population groups in Israel, we have examined clinical and biologic markers in patients diagnosed with prostatic cancer in Southern Israel in 1996-2000. We wanted to demonstrate differences in the incidence and features of prostate carcinoma among the population groups in Southern Israel, and to evaluate their possible biologic significance. METHODS: Clinical parameter features, including the ethnicity origin of patients with prostatic adenocarcinoma, were reviewed in a cohort of 189 patients seen between 1996 and 2000. Tissue sections from specimens in a subset of 40 of these patients who had undergone prostatectomy were studied by immunohistochemistry for TP53, Bcl-2, and chromogranin A using the ABC peroxidase method. These markers were chosen because of their suggested impact on the biology of this tumor. Clinical correlations were examined. RESULTS: We confirm the presence of ethnic differences in the features of prostatic adenocarcinoma in our geographic area. Notably, patients of North African origin were treated surgically at a younger age than immigrants from East Europe. Higher total prostate-specific antigen levels and more robust tumor cell Bcl-2 expression were detected in the East European patients. The number of Bedouin subjects in our cohort of patients with prostatic cancer was much more limited than expected. No immigrants from Ethiopia were included in our study diagnosed with prostate carcinoma during this period. CONCLUSIONS: The proportion of patients of European, especially East European, origin was relatively high among the cohort of 189. Their older age and the lower proportion of subjects that underwent surgery, together with the tendency toward higher total prostate-specific antigen levels and higher Bcl-2 expression, suggest that this ethnic group may not differ significantly from the African-American group in the United States. The low representation of Bedouin and absence of Ethiopian immigrants among our patients with prostate cancer may point to a genuinely low incidence or it may be related to inadequate medical supervision in these population groups.     

Detection of prostate specific antigen in pancreas and salivary glands: a potential impact on prostate cancer overestimation

Purpose

We explored the immunohistochemical expression of prostate specific antigen (PSA) in pancreas and salivary glands.

Materials and Methods

We investigated 62 specimens from male and female subjects, representing normal cases and several pathological conditions of pancreas and salivary glands. Two commercially available monoclonal antisera for PSA and 1 for prostatic acid phosphatase were used.

Results

A consistently positive reaction for PSA and prostatic acid phosphatase, independent of patient sex, was noted in ductal cells of normal pancreas and normal salivary glands, as well as pleomorphic adenoma, adenocarcinoma and all oncocytic epithelial cells of Warthin's tumor. Reaction was absent in normal stromal and acinar cells, and squamous carcinoma.

Conclusions

PSA is detectable in normal and cancer tissues far from the prostate. Therefore, we may not entirely rely on specificity of PSA alone to diagnose metastatic prostate cancer.     

Immunohistochemical diagnosis of a case of metastatic prostate cancer to breast

Bilateral breast mass was found in a 71-year-old male who had been placed on estrogen therapy for stage D2 prostatic adenocarcinoma. Microscopically the mass contained adenocarcinoma morphologically similar to that of the prostate, but the differential diagnosis was impossible between metastatic prostatic carcinoma and primary breast carcinoma. Formalin-paraffin sections of both tumors were stained positively by PSA (prostatic specific antigen) and PAP (prostatic acid phosphatase) using B-SA (biotin-streptavidin) system technique and prostatic origin of the breast mass was confirmed. Prostatic origin for metastatic carcinoma in the breast is are with only 30 reported cases in the literature including 5 Japanese cases. In most of them the diagnosis of the breast lesion as prostatic carcinoma has been made on morphologic and clinical grounds only. Accurate diagnosis is important for the prognosis of the patient, and immunohistochemical method is useful for he diagnosis of breast carcinoma metastasized from prostatic origin.     

A case of ductal adenocarcinoma of the prostate treated with endocrine therapy and radiation therapy

We report a case of ductal adenocarcinoma of the prostate. A 81-year-old man presented with a complaint of microhematuria. Serum prostate specific antigen (PSA) was 18. 44 ng/ml. A cystourethroscopic examination revealed a papillary tumor near the verumontanum. Transurethral resection of the tumor and transrectal prostatic needle biopsy was carried out. The pathological diagnosis was ductal adenocarcinoma and acinar adenocarcinoma of the prostate. The tumor responded to endocrine therapy and radiation therapy. At the follow up at 18 months, the PSA level was in the undetectable range (＜0.01 ng/ml), and no reccurence of the tumor was seen. Pathogenesis and management of this rare condition is discussed.     

Primary mucin-producing urothelial-type adenocarcinoma of prostate: report of 15 cases

Prostatic urothelial-type adenocarcinoma arises through a process of glandular metaplasia of the prostatic urethral urothelium and subsequent in situ adenocarcinoma sometimes associated with villous adenoma. These prostatic adenocarcinomas are analogous to nonurachal adenocarcinomas arising in the bladder from cystitis glandularis. Only 2 cases of urothelial-type adenocarcinoma from an institution other than our own have been previously described. The distinction between adenocarcinoma from another organ secondarily involving the prostate, usual adenocarcinoma of the prostate, and prostatic urothelial-type adenocarcinoma can present a significant diagnostic challenge and has significant therapeutic implications. Fifteen cases of prostatic urothelial-type adenocarcinoma were retrieved from the consult files of one of the authors. Mean patient age at diagnosis was 72 years (range 58 to 93 y). All men had negative colonoscopies, clinically excluding a colonic primary. Bladder primaries were ruled out clinically or pathologically in radical resection specimens. Follow-up was available on all men with a mean of 50.3 months (range 2 to 161 mo). All men presented with urinary obstruction symptoms with 3 (20%) also having mucusuria and 2 (13.3%) also having hematuria. Four men (26.7%) developed metastatic disease and 8 (53.3%) died of disease. In 8/15 (53%) cases, glandular metaplasia of the prostatic urethra and contiguous transition to adenocarcinoma were identified. Multiple histologic patterns were observed including dissection of the stroma by mucin pools 15/15 (100%), villous features 7/15 (47%), necrosis 2/15 (13.3%), signet ring cells 3/15 (20%), perineural invasion 1/15 (6.7%), focal squamous differentiation 1/15 (6.7%), and a granulomatous inflammatory response 1/15 (6.7%). Immunohistochemical stains were negative for prostate specific antigen, prostate specific acid phosphatase, CDX2, and beta-catenin in all cases. Stains were positive for high molecular weight cytokeratin in 12/12 cases (100%), and CK7 and CK20 in 10/12 cases (83.3%). Prostatic urothelial-type adenocarcinoma is a rare aggressive cancer arising in the prostate. The differential diagnosis includes conventional prostatic mucinous adenocarcinoma and secondary infiltration from a colonic or bladder adenocarcinoma. Immunohistochemistry for prostate specific antigen, prostate specific acid phosphatase, and high molecular weight cytokeratin along with morphology can help rule out conventional prostate carcinoma. beta-catenin, CDX2, and clinical studies are needed to rule out colonic adenocarcinoma. As prostatic urothelial-type adenocarcinoma is entirely analogous to bladder adenocarcinoma in both, its morphology and immunophenotype, only clinical studies or in some cases pathologic examination of the cystoprostatectomy specimen can exclude infiltration from a primary bladder adenocarcinoma.     

Two cases of mucinous adenocarcinoma of the prostate]

We report two cases of mucinous adenocarcinoma of the prostate. A 56-year-old man underwent subcapsular prostatectomy under the diagnosis of benign prostatic hyperplasia in 1968, and was found to have mucinous adenocarcinoma of the prostate, which proved to be prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) positive, and carcinoembryonic antigen (CEA) negative by immunohistochemical staining. Subsequently he received 70 Gy of irradiation to the prostate, but died in 1976, when serum PAP was elevated. Autopsy revealed metastases to the liver, lungs, bone, peritoneum, spleen, pancreas, lymph nodes, and no primary gastrointestinal adenocarcinoma. The other case was a 57-year-old man, who underwent transurethral resection (TUR) for papillary tumor located just lateral to the verumontanum in 1982. The tumor was misdiagnosed as adenomatous polyp, and was PSA and PAP negative, and CEA positive. After 3 TURs of the recurrent tumor on the prostatic urethra, he underwent prostatourethrectomy, pelvic lymphadenectomy, and cystostomy for radical cure in 1985. The specimen proved to be mucinous adenocarcinoma of the prostate. He suffered recurrence of the tumor in the retrovesical space in 1987, and died in 1990. Autopsy revealed no evidence of metastasis except the local recurrence and no primary gastrointestinal adenocarcinoma.     

Age-related changes in tissue levels of prostatic acid phosphatase and prostate specific antigen

Immunoperoxidase localization of prostatic tissue antigens has become useful in identifying the prostate as the origin of metastatic disease. Much research has been aimed at investigating the presence of these antigens in the adult prostate gland in benign and neoplastic states. Few studies have been done to determine the presence of these markers before puberty. We studied the prostate gland of 42 children of varying ages to determine the presence of these antigens at all age ranges to puberty. Sequential sections of the prostate were cut for prostate specific antigen, prostatic acid phosphatase, and hematoxylin and eosin staining. The degree of immunoperoxidase stain was graded from 0 to 4. The results showed that staining levels of prostate specific antigen and prostatic acid phosphatase were high at birth, decreased by age 6 months, reappeared by age 10 years and increased to puberty. Thus, the levels of prostate specific antigen and prostatic acid phosphatase appear to follow the testosterone levels, suggesting a hormonal dependence.