Adenocarcinomas of the prostate induced by N-nitroso-N-methylurea in rats pretreated with cyproterone acetate and testosterone

Prostatic adenocarcinomas were induced in 5 out of 20 Wistar rats upon a single administration of 50 mg/kg N-nitroso-N-methylurea (NMU). The rats were pretreated with a daily dose of 50 mg/kg cyproterone acetate for 3 weeks followed by 3 daily injections of 100 mg/kg testosterone. All tumours developed in the dorsolateral prostate and were invasively growing. In 2 cases distant metastases were found. Three proliferative lesions classified as carcinomas in situ were also found in the dorsolateral prostate. A total of 7/20 animals (35%) carried an adenocarcinoma and/or a carcinoma in situ. In addition, 6 epithelial hyperplasias were observed in the dorsolateral and 1 in the ventral prostate of non-tumour-bearing rats. The method described may provide a good animal model for cancer of the prostate and lead to a better understanding of prostatic carcinogenesis.     

Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies.

Prostatic adenocarcinoma commonly metastasizes to bone. Unlike most other bony secondaries, the majority of skeletal prostatic metastases are osteoblastic rather than osteolytic in nature. Several growth factors which are known to stimulate bone formation are expressed in benign and malignant prostate cells, but none has been specifically linked to osteosclerotic metastases. Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo. We have reported previously that BMP-6 mRNA and protein are expressed in the majority of primary prostatic carcinomas with established skeletal metastases but rarely in clinically organ-confined tumours. This study examines the expression of BMP-6 mRNA in matched prostatic primary and secondary bony lesions and in isolated skeletal metastases from prostatic adenocarcinomas, as well as other common human malignancies, by in situ hybridization. BMP-6 mRNA was detected in 11 out of 13 bone metastases from prostate carcinoma and in three paired samples of primary prostate carcinoma and matching skeletal metastasis. Weak signals for BMP-6 were also present in 5 out of 17 skeletal deposits from non-prostatic malignancies. BMP-6 mRNA appears to be strongly expressed in prostatic adenocarcinomas, both in the primary tumour and in bone metastases. It is also expressed, though less frequently, in skeletal metastases from other human carcinomas. Our findings suggest that BMP-6 may hold potential as an attractive marker and possible mediator of skeletal metastases, particularly in prostate carcinoma.     

A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential

Neuroendocrine (NE) cells may be involved not only in growth and differentiation of the normal prostate but also in carcinogenesis and progression of prostate adenocarcinoma (Pca), including development of androgen resistance. However, the exact pathophysiology of NE cells in Pca remains poorly understood. Here we describe a transgenic model of Pca with progressive NE differentiation. Seven lines of transgenic mice with the rat prostate-specific large probasin promoter linked to the SV40-large T antigen (Tag) that develop prostatic neoplasia have been established. In this study, one of the seven lines (12T-10) was characterized by examination of 52 mice aged from 2-12 months. With advancing age, low-grade prostatic intraepithelial neoplasia, high-grade prostatic intraepithelial neoplasia, microinvasion, invasive carcinoma, and poorly or undifferentiated carcinoma with NE differentiation appeared in the prostates in sequential order. Whereas Tag is expressed uniformly in prostate epithelium, only an increasing subset of cells in prostatic intraepithelial neoplasia showed NE differentiation by chromogranin immunostaining. Frankly invasive carcinoma developing subsequently showed occasional definitive glandular differentiation (adenocarcinoma) and particularly undifferentiated carcinoma with NE histological features similar to those observed in NE carcinomas in humans. The NE carcinomas occurred in the dorsolateral and ventral lobes and were generally androgen receptor negative. Twenty-one of 32 (66%) mice aged > or = 6 months and 15 of 17 (88%) mice aged > or = 9 months developed metastatic tumors, as confirmed by histology and/or Tag immunohistochemistry. Metastases occurred at the later time points, with metastasis to regional lymph nodes, liver, and lung being particularly common. Metastases showed histological features of NE differentiation, as confirmed by chromogranin immunostaining and electron microscopy. An athymic nude mouse that received a s.c. implant of a primary NE tumor developed Tag-positive metastatic tumors with similar NE differentiation. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified identical protein profiles between the primary NE tumor and lesions in the extraprostatic organs. Hence, in the 12T-10 large probasin promoter-Tag mouse, high-grade prostatic intraepithelial neoplasia develops progressively greater NE differentiation and progresses to invasive adenocarcinoma and NE carcinoma, with a high percentage of metastases. The predictable progression through these stages will allow testing of therapeutic interventions as well as possible further delineation of the role of NE cells in Pca progression.     

Differences in the leucine aminopeptidase activity in extracts from human prostatic carcinoma and benign prostatic hyperplasia.

Extracts of tissue showed that prostatic carcinomas contain less leucine aminopeptidase activity than benign prostatic hyperplasia. This is true when activity is expressed as specific activity (P = 0.0033), specific activity/% epithelium (P = 0.0007), activity/wet weight of tissue (P = 0.0028), or activity/wet weight of tissue/% epithelium (P = 0.0005). Almost all histochemically demonstrable activity is located in the epithelium. Enzymatic activities in extracts and in histochemical preparations showed similar differences between carcinoma and benign prostatic hyperplasia and were related (R = -0.38, P = 0.0400) to Gleason's grades. The transurethrally resected prostate cancers studied contained no well-differentiated tumors and a high proportion of poorly differentiated tumors. Histochemical activity is absent in most prostatic carcinomas and decreased in others. This observation is particularly interesting in view of the growing knowledge of tumor suppressor genes.     

Monoclonal-antibody pd-41 recognizes a prostate-cancer associated antigen whose expression increases in metastases and following hormonal-therapy

Tissues of prostatic origin representing variable phenotypes were tested for reactivity to the prostate cancer specific mouse monoclonal antibody PD-41. Avidin biotin immunoperoxidase was applied on formalin-fixed, paraffin-embedded tissue sections of 15 benign prostatic hyperplasia (BPH), 23 prostatic intraepithelial neoplasia (PIN), 14 untreated primary adenocarcinoma, 35 diethylstilbestrol (DES) treated tumors, 50 lymph node and 11 bone metastases. Specimens were stratified according to the percentage of tumor cells expressing PD-41 antigen and degree of staining intensity, and correlated with PIN grade, Gleason score, flow cytometry (FCM) measured DNA ploidy, and reactivity to other antibodies. In PIN, 4 specimens (17.4%) showed reactivity in a significant number of cells while a few cells were reactive in most cases. PD-41 was significantly reactive (>5% of tumor cells) in 88% of nodal metastases and in 73% of bone metastases in contrast to 49% reactivity in primary tumors (p=0.0003). There was a tendency of increased antigen expression in hormonally treated primary tumors. In addition, involutional and metaplastic changes in hormonally treated cases were reactive in many instances. Semi-quantitative evaluation of PD-41 reactivity showed a statistically significant correlation with Gleason score in primary tumors (p=0.007) and in lymph node metastases (p=0.009). Moreover, the PD-41 antibody reacted in metastatic lesions that failed to express both prostatic acid phosphatase and prostate specific antigen. These data suggest that monoclonal antibody PD-41 merits further investigation to evaluate its potential diagnostic, prognostic and therapeutic role in prostate cancer.     

18F-FDG PET显像在原发灶不明转移癌中的应用价值

目的 转移性肿瘤原发灶的定位对指导组织学诊断及选择治疗方式具有重要意义。本文对50例原发灶不明转移癌患者进行~(18)F-FDG PET全身显像,以评价其在探测原发灶中的价值。 方法 50例原发灶不明转移癌患者,男36例,女14例,其中颈部转移瘤18例,骨骼转移瘤15例,脑转移瘤12例,其他5例。所有患者均进行FDG PET全身显像,结果判断应用目测法和半定量分析方法(标准摄取值,SUV)。 结果 50例患者中,有32例PET可检出原发灶(64％),且经组织学或细胞学证实,其中肺癌17例,鼻咽癌9例,乳腺癌2例,卵巢癌、结肠癌、前列腺癌、甲状腺癌各1例。2例(4％)FDG PET呈假阳性,分别为子宮和结肠病变各1例。18例FDG PET显像原发灶不明者,经临床随访2～26个月,有2例发现原发灶,1例证实为前列腺癌,1例为粘液性胃癌。17例患者PET检出了其他部位的转移灶。 结论 PET一次检查可了解肿瘤原发灶及全身转移情况,包括骨骼及软组织的转移,对原发灶不明转移癌患者进行全身PET检查有助于原发灶的寻找,为临床制订治疗方案提供可靠依据。     

Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors

In colorectal tumors, S-phase kinase-associated protein 2 (Skp2) still has numerous important questions unanswered: its expression in adenomas, its correlation with key clinicopathological indices, its association with patient prognosis, its variation in lymph node metastases, and its association with many cell-cycle regulators. To answer these questions in colorectal tumors, Skp2, cyclin A, cyclin B1, cyclin E, CDK2, and Ki67 were immunohistochemically stained in 12 normal mucosa, 36 adenomas, 11 carcinomas in adenomas, 102 primary carcinomas, and 12 paired lymph node metastases; and Skp2 was examined by Western blot in 8 pairs of normal mucosa and carcinomas. Situated in nuclei, Skp2 expression significantly increased from normal mucosa through adenoma to primary carcinoma (p<0.0001), from mild through moderate to severe dysplasia in adenomas (p=0.038), from peripheral adenoma to paired central carcinoma (p=0.0033), and from primary carcinoma to lymph node metastasis (p=0.015), and these increases were confirmed by Western blot. Expression, however, relatively declined significantly in the primary carcinomas showing deep invasion (p=0.0113), lymph nodal metastases (p=0.0268), and poor prognosis for all (p=0.0104) or stage III patients (p=0.0119). High Skp2 was also significantly linked with elevated cyclin A, cyclin B1, cyclin E, CDK2 (in primary carcinomas only), and Ki67 in both adenomas and primary carcinomas. Thus, overexpression of Skp2 is associated with colorectal carcinogenesis and late metastasis to lymph nodes, whereas relative reduction of Skp2 is correlated with local invasion of primary carcinoma.     

Inhibin-like material--an immunohistologic marker for prostatic origin of metastases

Immunocytochemical localization of inhibin-like material (ILM) using a specific antiserum generated against ILM of prostatic origin was carried out in metastatic lymph nodes of known primary prostatic tumours and in rectal biopsies showing direct invasion with known prostatic carcinoma. Nine of the 11 metastatic lymph nodes gave positive reaction, which was readily apparent in differentiated tumours showing micro-acinar formation. In poorly differentiated tumours it was often focal and indicated intracytoplasmic staining within randomly scattered cells. Rectal biopsies showing invasion of prostatic carcinoma (4 cases) also showed positive reaction for ILM. Using this experimental protocol, the reaction for metastatic lesions from patients with non-prostatic carcinomas was completely negative indicating the specificity of the test for prostatic origin of metastasis. In conclusion, the present investigation indicates the potential application of ILM in confirming or excluding the prostatic origin of invasive tumour in metastatic lesions.     

Prostate carcinoma skeletal metastases: cross-talk between tumor and bone

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.     

Relationship between DNA ploidy, glandular differentiation, and tumor spread in human prostate cancer

DNA ploidy was evaluated by flow cytometry for 45 human prostate carcinomas (34 prostatectomy specimens and 11 biopsies). Twenty tumors (44.4%) contained a distinct aneuploid stem line. All 11 tumors confined to the prostate gland (pathological Stage B) were diploid. The frequency of aneuploidy increased with advancing stage, and most tumors with distant metastases were aneuploid. The degree of glandular differentiation was characterized by the Gleason score. One-third of tumors with a Gleason score of 5 to 6 were aneuploid, whereas over 70% of poorly differentiated tumors with a Gleason score of 9 to 10 were aneuploid. Among diploid tumors, 45.5% were localized carcinomas (Stage B), 36.4% were characterized by invasion outside the prostate (Stage C), and 18.2% formed pelvic nodal or distant metastases (Stages D1 and D2). In nearly two-thirds of patients with aneuploid tumors, pelvic nodal or distant metastases were found. When tumors were classified according to both DNA ploidy and degree of glandular differentiation, then subgroups of tumors with the highest and lowest degree of malignant potential became apparent. Only 7.1% of diploid tumors with a Gleason score of 5 to 6 formed metastases, but 80% of aneuploid tumors with a higher Gleason score (7 to 10) formed metastases. Diploid tumors with higher Gleason scores and aneuploid tumors with lower Gleason scores had intermediate frequencies of metastases. The presence of an aneuploid stem line in prostate carcinomas indicated that the tumor had spread outside the prostate gland or had metastasized. DNA ploidy may be an important prognostic factor for human prostate cancer. DNA ploidy and the degree of glandular differentiation considered together may improve prognostic evaluation of prostate carcinomas.     

Topographical analysis of p53 expression and DNA ploidy in early bronchial squamous cell carcinoma and preneoplastic lesions.

The significance of p53 mutations and DNA aneuploidy in carcinoma cells has been investigated on the basis of a multi-step development theory of carcinogenesis. It has, however, not been determined whether these alterations can be used as diagnostic markers for the early detection of bronchial squamous cell carcinoma (BSqCC). To address this problem, we topographically investigated p53 alterations and DNA aneuploidy in 24 X-ray-negative, early BSqCC patients with various preneoplastic lesions and in 25 non-carcinoma patients with preneoplastic lesions. Bronchial lesions (n=88) were morphologically classified as hyperplasia (HP, n=5), squamous metaplasia (SM, n=23), low-grade dysplasia (LGD, n=14), high-grade dysplasia (HGD, n=11), intraepithelial carcinoma including 'carcinoma in situ' (CIS) (IEC, n=15), and microinvasive carcinoma (MIC, n=20). Immunohistochemistry for the p53 protein and image cytometry for DNA ploidy detection were performed in serial sections of each lesion. Overexpression of p53 protein was detected in 36, 73, and 65% of the HGD, IEC, and MIC lesions, respectively. Aneuploid DNA profiles were found only in carcinoma lesions, 33% in IEC and 85% in MIC. The topographical analysis revealed two types of early BSqCCs, one with adjacent preneoplastic lesions (sequential type, n=8) and another without such lesions (de novo type, n=16). The p53 protein was frequently overexpressed in both types (sequential type, 79%; de novo type, 62%). In the sequential type, however, the p53 protein was overexpressed in HGD lesions that were directly adjacent to p53-overexpressing carcinoma lesions without exception. The present topographical study suggests that p53 mutations play an important role in the carcinogenesis of BSqCC and that p53-overexpressing HGD lesions in sequential types should be regarded as 'truly' preneoplastic lesions that actually develop into carcinomas. In addition, our study demonstrated that DNA aneuploidy might occur at times after p53 alteration with increasing frequency, as invasive growth begins. Such combination analysis of p53 immunohistochemistry and nuclear DNA ploidy in routine histology may contribute to estimates of malignant potential in preneoplastic and intraepithelial squamous lesions and provide additional information for early detection of BSqCC.     

Establishment and Characterization of Three Androgen-independent, Metastatic Carcinoma Cell Lines from 3,2'-Dimethyl-4-aminobiphenyl-induced Prostatic Tumors in F344 Rats

Three stable carcinoma cell lines, designated PLS10, PLS20 and PLS30, have been established from 3,2'-dimethyl-4-aminobiphenyl plus testosterone-induced carcinomas in the dorsolateral prostate of male F344 rats. The cells are keratin-positive and grow as typical epithelial monolayers in culture. When injected into intact male nude mice, PLS10 and PLS30 cells form well-differentiated adenocarcinomas with abundant connective tissue stroma, while PLS20 cells give rise to poorly differentiated adenocarcinomas. Growth of all PLS cell lines in nude mice is not affected by castration and the cells are immunohistochemically negative for androgen receptors. Tumor growth rates in nude mice were found to be PLS20 > PLS10 > PLS30, with significant in vitro stimulation by insulin/transferrin, but not epidermal growth factor, dexamethasone or basic fibroblast growth factor. Spontaneous lung metastases were observed in all cases. However, skeletal invasion including bone is essentially observed only with the PLS20 tumors. Gelatin zymography showed predominant secretion of the active form of gelatinase B (Mr 92,000 type IV collagenase) by all the cell lines. Karyotype analysis revealed PLS10, PLS30 and PLS20 to be diploid, hyperdiploid and hypertetraploid, respectively. The results demonstrate that the three PLS cell lines are androgen-independent and metastatic in common, but have different histology, growth potential and invasiveness. They may therefore be useful models for understanding progression and metastasis of human prostatic carcinomas.     

Prostate cancer induction in autoimmune rats and modulation of T cell apoptosis

In this study we present an experimental model of prostate gland cancer induced by long term hormonal treatment with testosterone in combination with a chemical carcinogenic agent in male Wistar rats with autoimmune prostatitis (AIP). This system is particularly attractive in order to study the factors involved in the transition from a non-invasive to an invasive carcinoma, decisive in the risk of human cancer. At first, autoimmune prostatitis was induced by immunization in 3 months-old male Wistar rats with autologous accessory glands. Then, rats were treated with continuous intradermal implants of testosterone propionate (TP) and with single doses of the chemical carcinogen 7, 12 dimethylbenz (alpha) anthracene (DMBA) by intraperitoneal injection. Histopathological studies of the prostate gland revealed the presence of pre-malignant lesions, particularly the so-called prostatic intraepithelial neoplasm (PIN) in 50% of animals. Moreover, we observed the development of carcinomas in 50% of treated-animals, which could be histologically discriminated in adenocarcinomas, carcinoma of epidermal origin and undifferentiated carcinoma. In autoimmune rats which did not receive any other treatment, exposure to autoantigens gave rise to an atypical hyperplasia of the prostatic gland which could be attributed to the hyperactive state of the gland. Control groups constituted by autoimmune rats treated with TP or DMBA, and normal rats which were exposed to TP and/or DMBA evidenced the presence of PINs at different degrees, but did not develop carcinomas. Moreover, serum acid phosphatase significantly increased as treatment was accomplished, reaching its maximum levels in animals with carcinoma, in which DNA content, determined by image cytometry, showed to be aneuploid. Finally, we provided biochemical and cytofluorometrical evidence of the induction of apoptosis of spleen T cells in carcinoma-bearing hosts, and to a lesser extent in animals with PIN, but not in autoimmune or normal controls, which could represent an alternative molecular mechanism for explaining host immunosuppression triggered by tumors.     

Papillary adenocarcinomas of the prostate. An immunohistochemical study

Five cases of papillary adenocarcinomas of the prostate were studied for prostate-specific acid phosphatase, using the immunoperoxidase method, to determine the origin and histogenesis of these uncommon tumors. All five cases were prostatic-acid-phosphatase positive, whereas four cases showed in situ carcinoma involving large periurethral ducts. Positive immunohistochemical localization of prostate-specific acid phosphatase is useful in identifying papillary carcinoma of true prostatic origin and distinguishing them from prostatic-acid-phosphatase-negative carcinomas which may include tumors arising from periurethral glands or metaplastic urethral mucosa.     

Expression of nm23-Hl and nm23-H2 Proteins in Prostate Carcinoma

The nm 23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm 23-H1 and nm 23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm 23-H1 or nm 23-H2 protein, respectively. Negative staining for nm 23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm 23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm 23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm 23-H2 protein was detected in 83% of primary tumors and its expression appeared to he significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm 23-H1 and nm 23-H2 expression. These data suggest that the nm 23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.     

Target validation of cytochrome P450 CYP1B1 in prostate carcinoma with protein expression in associated hyperplastic and premalignant tissue

PURPOSE: To investigate the localization and distribution of cytochrome P450 CYP1B1 protein expression in patients diagnosed with prostate carcinoma compared to those with bladder carcinoma. To validate CYP1B1 as a molecular target for the development of selective cancer therapeutics for use in combination with radiation. METHODS AND MATERIALS: Prostatectomy specimens (n = 33) of moderate Gleason grade (3 + 3 and 3 + 4) were analyzed immunohistochemically for CYP1B1 protein expression using a specific monoclonal antibody for the enzyme. The intensity of CYP1B1 staining was assessed both semiquantitatively using visual scoring and quantitatively by spectral imaging microscopy using reference spectra and compared with bladder carcinoma (n = 22). RESULTS: CYP1B1 protein expression was present in 75% of prostate carcinomas (n = 27) compared to 100% of bladder carcinomas (n = 22). In both cases, CYP1B1 protein expression was heterogeneous and localized in the cytoplasm of the tumor cells but absent from the surrounding stromal tissue. CYP1B1 was also detected in premalignant prostatic intraepithelial neoplasia (n = 2, 100%), as well as noncancerous tissues, including benign prostatic hyperplasia (n = 27, 82%), metaplastic prostatic urothelium (n = 8, 100%), and hyperplastic prostatic urothelium (n = 14, 100%). Higher CYP1B1 protein expression in bladder vs. prostate carcinoma was confirmed by their corresponding average normalized absorbances (+/- standard deviation), measured as 1.40 +/- 0.44 and 0.55 +/- 0.09, respectively. Overall CYP1B1 staining intensity in prostate carcinoma was similar to that in prostatic intraepithelial neoplasia, benign prostatic hyperplasia, and hyper-/metaplastic urothelial tissue. No CYP1B1 was detected in normal prostate tissue. CONCLUSIONS: CYP1B1 is overexpressed in prostate carcinoma at a high frequency and is also detectable in the associated premalignant and hyperplastic tissue, implicating a possible link with malignant progression and CYP1B1 as a suitable target for therapy. Spectral imaging microscopy has highlighted differences in CYP1B1 protein expression between different cancers.     

The histogenesis of small cell carcinoma of the prostate. An immunohistochemical study

Small cell carcinomas of the prostate are rare. A few reported cases have manifested morphologic and functional neuroendocrine characteristics, and it has been suggested that these tumors are derived from the argentaffinic/argyrophilic cells normally present in the prostate. The authors have recently studied three cases of primary prostatic small cell carcinoma in which the small cell component developed during the course of progression of "regular" prostatic adenocarcinoma, and reflected a terminal aggressive phase of the disease. Immunoperoxidase staining for prostate-specific acid phosphatase (PSAP) showed positivity in the adenocarcinoma but absence in the small cell component of each tumor. The association of small cell carcinoma with prostatic adenocarcinoma indicates that in considering the histogenesis of prostatic small cell carcinoma, a specific neuroendocrine cell of origin need not be implicated.     

Adenocarcinoma of the prostate with endometrioid features. A light microscopic and immunohistochemical study of ten cases

The authors reviewed the histologic slides of 2600 prostatic carcinomas seen at Memorial Hospital from 1963 to 1983. In ten cases, resection specimens had a predominantly endometrioid appearance. Six patients had polypoid lesions in and around the verumontanum, and one had a polypoid lesion away from the verumontanum. Two patients had no mucosal lesions and one was not cystoscoped. Histologically, the tumors showed a tall pseudostratified columnar epithelium, usually with amphophilic cytoplasm. The cells were arranged either along papillae or in complexes of large acini or in single glands. In eight of the ten cases, the endometrioid carcinomas were associated with a prior or coexistent typical microacinar prostatic adenocarcinoma. In four cases, the endometrioid pattern existed in a pure form, although in two such cases with urethral tumors, the patients had histories of successfully treated microacinar adenocarcinomas of the posterior prostatic lobe. In one case, a urethral endometrioid tumor coexisted with a small posterior lobe microacinar adenocarcinoma. In five cases, both endometrioid and microacinar carcinomas were seen, including endometrioid and microacinar carcinomas found at the same site at different times (2 cases), tumors with a predominantly endometrioid, yet focally microacinar pattern (1 case), and primary tumors where lymph node metastases had different histologic features (2 cases). Of the three patients with a pure or predominantly endometrioid pattern treated with diethylstilbestrol, two had a marked clinical response. All ten endometrioid prostatic adenocarcinomas showed prostate-specific antigen and prostate-specific acid phosphatase immunoreactivity, in contrast to none of the control uterine endometrial carcinomas. In material spanning a 20-year period, the authors have not seen a single prostatic tumor entirely analogous to the uterine endometrial carcinoma. Until such proof exists, prostatic carcinomas with endometrioid features are best classified and treated as variants of prostatic duct carcinomas.