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Several studies have reported on the use of antibodies to monoclonal carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably enthusiastic results. It is still unclear whether site of origin or pathway of differentiation (endometrioid [em] versus mucinous [m]) is more important in predicting immunohistochemical differences. In the present study, paraffin blocks from adenocarcinomas of known origin were retrieved and immunostained with monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20, estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors with mixed patterns received separate scores for the em and m foci). Mean CEA scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1, and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6; PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20, 0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with the latter more important for VIM and PR, the former for ER, both for CEA (only mEC was frequently strongly positive), and neither for the CKs studied. No one stain or combination reliably distinguished endometrial from endocervical origin. The only immunostaining pattern that might identify a site of origin with more accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in this series an endometrial origin of the tumor.

Objective: To report a case of secondary amenorrhea and infertility caused by an inhibin-B-producing ovarian fibrothecoma., Design: Case report., Setting: Academic medical center., Patient: A 37-year-old woman with a 2-year history of secondary amenorrhea and infertility., Intervention(s): Operative removal of a 5-cm ovarian fibrothecoma., Main Outcome Measure(s): Luteinizing hormone, FSH, E2, inhibin-B, TSH, and prolactin measured preoperatively and postoperatively. Immunostaining of tumor cells for inhibin and LH., Result(s): Preoperative hormone levels were as follows: FSH, 1.7 mIU/mL; LH, 23.4 mIU/mL; E2, 31 pg/mL; and inhibin B, 1,154 pg/mL. Three weeks postoperatively, the FSH was 1.5 mIU/mL, LH decreased to 7.1 mIU/mL, E2 increased to 276 pg/mL, and inhibin-B decreased to 17 pg/mL. The fibrothecoma did not stain for LH but was strongly positive for inhibin. Regular menstrual cycles resumed 28 days postoperatively., Conclusion(s): Inhibin-B produced by an ovarian tumor profoundly suppressed FSH levels and resulted in secondary amenorrhea and infertility. Use of sensitive and specific immunoassays for inhibin-A and -B may aid in the differential diagnosis of hormonally active ovarian tumors.

The histopathologic grade of ovarian epithelial carcinoma has generally been found to be of prognostic significance, but the grading system used has varied among published reports, and often has not been specified at all. The major proposed grading systems are reviewed, and a new system is proposed, which is modeled on the Nottingham system of breast cancer grading and is designed to be applied to all invasive epithelial carcinomas of the ovary. Results obtained in studies using this system are presented. When grading is compared with histopathologic typing of ovarian carcinoma, the latter is less valuable in predicting survival but better at predicting tumor responsiveness to chemotherapy, and can also suggest the chemotherapeutic agents to be used. Thus, both grade and type should be specified in the surgical pathology report for any ovarian carcinoma.

Objective: Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems--both architectural and cytologic features, as well as mitotic activity and histologic tumor type--to determine which of these components fit best with survival., Methods: We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival., Results: The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not., Conclusion: The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

Background: Most published series of ovarian carcinoma find a correlation between histologic grade and survival, but the grading system used commonly is not specified, and several different systems exist, some of which use different criteria for different histologic types. However, several studies have shown marked interobserver variability in distinguishing among the histologic types of ovarian carcinoma. The authors attempted to derive a universal grading system for all invasive ovarian carcinomas (IOC), based on the Nottingham system for grading all types of mammary carcinoma., Methods: The authors studied 461 patients with IOC of different histologic types and clinicopathologic stages who were treated in a uniform manner between 1980 and 1994 with surgery and cisplatin-based chemotherapy. All slides were reviewed and the tumors graded as follows: Architectural pattern (predominant): Glandular = 1, Papillary = 2, and Solid = 3; Nuclear pleomorphism: Slight = 1, Moderate = 2, and Marked = 3; Mitotic activity (mitotic figures per 10 high-power fields [1 HPF = 0.345 mm2]) in most active region: 0-9 = 1, 10-24 = 2, and > or = 25 = 3; Grade 1 = total score (adding three values obtained earlier) 3-5, Grade 2 = 6 or 7, and Grade 3 = 8 or 9., Results: Tumor grade correlated with survival in both early and advanced stage disease and for all major histologic types of IOC except clear cell carcinoma (CCC). Results for CCC approached but did not reach clinical significance. By multivariate analysis, only this tumor grade and performance status were significant in Stage I/II IOC. For Stage III/IV tumors, the new tumor grade also was significant, as were performance status, residual tumor size, response to chemotherapy, and mucinous (unfavorable) or transitional cell (favorable) histologic type. International Federation of Gynecology and Obstetrics grade (based primarily on architectural features) did not correlate significantly with survival except in Stage III/IV serous and Stage I/II mucinous carcinomas., Conclusions: The new grading system reported is simple, reproducible (among the current study authors), and useful for all histologic types and clinical stages of IOC. Further testing for reproducibility and clinical utility is recommended.

Primary transitional cell carcinoma (TCC) of the ovary has been recently recognized as a separate subtype of epithelial cancer. It has been proposed that recognition of such tumors is important on clinical grounds because of a favorable response to chemotherapy and an improved patient survival. The authors reviewed the histological and clinicopathologic findings of 58 patients with advanced stage (stages III and IV) ovarian cancer with a view to determining the frequency of TCC and confirming the favorable prognosis. Of these cases, 15 (26%) were reclassified as TCC; 13 were predominantly TCC, and 2 had a mixed pattern with approximately 50% of the tumor being TCC. TCC patients ranged in age from 44 to 70 years of age (mean, 57). Ten of the patients had stage III disease, and five were stage IV. The tumor was unilateral in 2 cases and bilateral in 11 (2 unknown). Tumor size varied between 3 and 23 cm. Of the stage III patients, five were optimally debulked, and five had residual disease. All patients received the same type of chemotherapy. The median overall survival was 28 months. There was no significant difference in the clinical outcome of patients with TCC compared with that of patients with serous carcinomas. These data suggest that TCC does not confer a favorable prognosis or better response rate to chemotherapy.

The presence of microinvasion (Mi) has not previously been investigated in nonserous low malignant potential (LMP) tumors of the ovary. In serous LMP tumors (SLMP), Mi has not worsened the prognosis compared with usual SLMP in previous reports. In a retrospective clinicopathologic review of 126 cases of serous and mucinous LMP (MLMP) tumors of the ovary, the authors identified 14 cases with Mi: seven of 72 SLMP, four of 44 mucinous intestinal LMP (MILMP), and three of 10 mucinous müllerian LMP (MMLMP). Tumors with Mi resembled usual LMP histologically except for small foci (up to 0.2 cm) in the stroma consisting predominantly of single cells or small clusters of cells, sometimes in a cribriform pattern. In SLMP-Mi, the cells had eosinophilic cytoplasm, and the stromal reaction was minimal/absent. In MILMP-Mi and MMLMP-Mi, nuclear staining was paler; the stroma often showed a fibrous reaction or edema, especially in MILMP-Mi. All 14 patients had follow-up (2.2 to 18.6 years) and were without evidence of disease. Careful screening of both mucinous and serous ovarian LMP can show Mi. Mi foci should be distinguished from true stromal invasion, pseudoinvasion, endothelial cells, decidual cells and histiocytes, and pseudomyxoma in mucinous LMP. Mi does not seem to worsen prognosis in MLMP and SLMP tumors of the ovary.

We have reviewed 44 mucinous intestinal (MI) and 10 mucinous mullerian (MM) tumors of low malignant potential (LMP) seen at The George Washington University Medical Center. As previously reported by Rutgers and Scully, MMLMP tumors occurred in younger women, were generally smaller and more frequently bilateral, had a papillary rather than multicystic appearance, and lacked goblet cells. All patients with MMLMP tumors were recurrence-free at last follow-up, including three whose tumors were microinvasive. Patients with MILMP tumors also all did well regardless of tumor grade, with the exception of a single patient with bilateral grade 1 ovarian tumors, an appendiceal villous adenoma, and pseudomyxoma peritonei. Microinvasion was also seen in four of these tumors, none of which recurred. Review of the literature suggests that MILMP tumors without stromal invasion but with either prominent cell stratification or marked nuclear atypia may have a worse prognosis than those lacking these features, but probably largely because of a correlation with higher stage disease. We believe that tumors of this sort should not be diagnosed as "noninvasive carcinomas," but should be sectioned more extensively for evidence of stromal invasion and subjected to careful staging. If the tumor is still noninvasive and in stage I after these procedures, the likelihood of treatment failure appears to be in the range of 1-3%.

The presence or absence of tubal mucosal epithelial proliferation (MEP) and its degree of severity when present were investigated in 191 cases, including 49 ovarian serous tumors of low malignant potential (LMP), 33 nonserous (predominantly mucinous) LMP tumors, various other benign and invasive malignant female genital tract lesions, and 37 cases (73 fallopian tubes) of tubal ligation for sterilization. MEP including all degrees of severity was found to be an almost ubiquitous (83% of all cases) lesion of no clinical significance. On the other hand, MEP of moderate or marked degree was rarely seen (3% of cases) in normal tubes obtained for sterilization, but was identified in from 25% to > 40% of tubes accompanying a wide variety of nonneoplastic and neoplastic lesions. Thus, we recommend that only moderate to marked MEP be considered as a diagnosable lesion in the future. There was no tendency in this material for MEP to show any specific association with ovarian serous LMP tumors, as was previously reported. However, when MEP was present, it was more likely to be widespread and mitotically active when it accompanied an ovarian LMP tumor of any histologic type than when it was found with benign ovarian lesions, invasive gynecologic cancers, uterine leiomyomas, or tubal inflammatory lesions and ectopic pregnancies.

Mature cystic teratomas of the ovary frequently contain intestinal-type tissues, but these rarely organize into complete intestinal walls, including all layers, and even more rarely develop secondary neoplasms. The present report documents two mature teratomas with formation of complete segments of intestinal wall, one also containing a benign mucinous cystadenoma of the appendiceal type and the other an intestinal-type adenocarcinoma infiltrating into the neoplastic bowel wall but not the surrounding ovarian parenchyma. The latter patient is alive and well 5 years after surgery. These cases expand the repertoire of secondary neoplasms, benign and malignant, developing in mature cystic teratomas.

In an attempt to clarify the histogenesis of carcinosarcoma (malignant mixed müllerian tumor) of the female genital tract, 20 uterine and eight ovarian tumors were studied by light microscopy, transmission electron microscopy, and immunohistochemistry. Cytokeratins (MAK-6 and AE1:AE3) and epithelial membrane antigen were detected in the epithelial component of all tumors and in the stromal component of 15 cases (55%). Vimentin was detected in the stromal component of all cases and was focally positive in the epithelial component of 18 cases (69%). Tumors showing rhabdomyosarcomatous or chondrosarcomatous differentiation were positive for myoglobin and S-100 protein, respectively. At the ultrastructural level epithelial cells were observed in tight clusters (usually surrounded by a basal lamina), in loose aggregates, and singly (sometimes spindle shaped), and were surrounded by cells displaying variable differentiation. The closest examples of "hybrid" epithelial/stromal cells were those with a prominent rough endoplasmic reticulum, cytoplasmic projections, poorly formed intercellular junctions, and an incomplete basal lamina. The observations support the view that carcinosarcomas of the female genital tract could represent examples of biphasic (metaplastic) carcinomas.

Abnormalities of epidermal growth factor receptor (EGFR) and c-erbB-2 have been demonstrated to be correlated with aggressive biologic behavior in a variety of human cancers. To analyze the possible roles of these oncogenes in ovarian neoplasms, immunolocalization of EGFR and c-erbB-2 oncogene product was performed in 45 cases of human ovarian mucinous and serous cystadenomas, carcinomas of low malignant potential (LMP), and invasive carcinomas by employing antibodies against these oncogene products. EGFR immunoreactivity was present in 15 of 35 LMP and invasive carcinomas and 1 of 10 cystadenomas. On the contrary, immunoreactivity of p185, which is an oncogene product of c-erbB-2, was detected only in five cases of carcinoma and in no benign cystadenoma. These results indicate that EGFR may be involved in the neoplastic process in epithelial ovarian adenocarcinoma, especially mucinous carcinoma, but involvement of c-erbB-2 is probably not as prevalent as considered previously. Four of the five cases immunohistochemically positive for p185 were also positive for EGFR, which suggests that expression of EGFR and p185 is to some extent correlated in human ovarian carcinoma.

Activation of c-myc oncogene has been reported in increasing numbers of human ovarian carcinomas and appears to play a role in the biologic behavior of the neoplasms. We have studied the immunohistochemical localization of p-62c-myc, the gene product of c-myc, in 44 cases of serous and mucinous cystadenoma, adenocarcinoma of low malignant potential, and invasive adenocarcinoma, using a monoclonal antibody raised to a synthetic human p62c-myc sequence (Myc 1-6E10). Both serous and mucinous cystadenomas demonstrated a higher frequency of nuclear localization than did carcinomas, which showed much greater cytoplasmic staining, while tumors of low malignant potential showed an intermediate pattern. However, the observed differences did not reach statistical significance. No significant correlation was observed between intracellular localization patterns of p62c-myc and histologic and nuclear grades and mitotic activity in the cases of carcinoma. Great care should be taken in the interpretation of immunohistochemical analysis of oncogene products, especially when attempting to correlate the findings with biologic tumor behavior.

The lectin-binding properties of 44 cases of serous and mucinous ovarian cystadenoma, tumor of low malignant potential (LMP), and invasive carcinoma were examined histochemically. Wheat germ agglutinin (WGA), concanavalin A (con A), Ulex europaeus agglutinin I (UEA-I), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), soybean agglutinin (SBA), and Robina pseudoaccacia (RPA) were employed. All the lectins examined were bound to neoplastic epithelial cells of benign and malignant tumors, but none bound exclusively to ovarian tumor cells. Different lectin-binding patterns between serous and mucinous neoplasms were observed, with the exception of RPA. UEA-I, con A, RPA, and PNA in serous neoplasms and UEA-I, RPA, and WGA in mucinous neoplasms demonstrated lectin-binding properties of LMP tumors intermediate between those of cystadenoma and invasive carcinoma. These findings indicate that serous and mucinous ovarian neoplasms contain different glycoconjugates, that malignant transformation of the neoplasms is associated with alteration of these glycoconjugates, and especially that LMP tumors have a different composition of cellular glycoconjugates from that of invasive ovarian carcinoma.

The altered expression of the human retinoblastoma (RB) gene has been demonstrated to play an important role in the pathogenesis of RB and other tumors. To determine whether the RB gene might be involved in the pathogenesis of human ovarian and endometrial cancer, DNA from 24 human ovarian tumors, 3 normal ovaries, 3 endometrial carcinomas, and 1 endometrial hyperplasia was examined with an RB complementary DNA probe. Evidence for homozygous deletion of the RB gene was observed in only one specimen. Interestingly, the specimen was an endometrioid tumor of the ovary of low malignant potential (LMP). This patient experienced rapid progression of the tumor and died 8 months after diagnosis. Abnormalities of the RB gene may be involved in the aggressive biologic behavior of certain forms of ovarian carcinoma, particularly those of LMP.

Ten granulosa cell tumors of the ovary were investigated using clinicopathologic and flow cytometric parameters. Three of the patients had recurrent or metastatic lesions 3 to 9 years after resection of the primary ovarian tumor. These three cases demonstrated diploidy in both the primary tumor and metastatic or recurrent lesions. Among the seven cases without recurrence, five had diploid DNA indexes. One case was characterized by a high degree of cytologic atypia and tetraploidy (DNA index, 1.98); this patient died of metastatic breast cancer 4 years after resection of the ovarian tumor. Another case demonstrated a high mitotic rate and exhibited aneuploidy (DNA index, 1.33); this woman was alive and well at 5 years of follow-up. In this study, no correlation was found between the recurrence rate and ploidy but, in view of the small numbers and limited follow-up, we cannot definitively analyze these prognostic factors. It does not appear feasible to predict the clinical course of granulosa cell tumors by DNA flow cytometry. However, it can be concluded that: (1) most granulosa cell tumors have diploid DNA content and (2) DNA ploidy correlates well with histologic factors, such as cellular anaplasia and high mitotic activity, which may have predictive prognostic value for granulosa cell tumors.

The reactivity of a new monoclonal antibody (MAb), MSN-1, raised against a human endometrial cancer cell line (SNG-II), was studied in a variety of endometrial, endocervical, and ovarian carcinomas as well as normal cycling endometrium. Moderate to strong reactivity (2-3+) was seen in six of nine normal secretory endometria (67%), one of 10 normal proliferative endometria (10%), 18 of 18 endometrial adenocarcinomas (100%), 10 of 11 endometrioid ovarian adenocarcinomas (91%), seven of nine clear cell ovarian adenocarcinomas (78%), one of 12 endometrial hyperplasias without atypia (9%), two of four endometrial hyperplasias with atypia (50%), zero of five endometrial serous adenocarcinomas, two of 17 serous ovarian adenocarcinomas (12%), zero of 10 intestinal-type mucinous ovarian adenocarcinomas, and zero of nine metastatic adenocarcinomas in ovary. Endocervical adenocarcinomas showed moderate to strong staining in 75% (six of eight). It is concluded that MSN-1 can be used to confirm endometrioid/clear cell differentiation in ovarian and endometrial tumors, cannot be used to discriminate endocervical from endometrial differentiation, cannot be used to discriminate atypical hyperplasia from carcinoma, and may be useful to distinguish between atypical (premalignant) endometrial hyperplasias and those without atypia.

We present five cases in which ovarian neoplasms (three clear cell carcinomas, two endometrioid carcinomas) were associated--and in four cases contiguous--with atypical glandular epithelial changes in endometriosis. This association has not been reported previously in the ovary, but four cases of extragonadal malignant tumors have been noted to occur with or after atypical endometriosis. We propose that a diagnosis of atypical endometriosis be followed by careful long-term observation of the patient to detect possible subsequent development of neoplasia.

Human yolk sac carcinomas have been studied only twice with the electron microscope, and have never been compared at this level with normal human yolk sac. In the present study, the ultrastructural features of three primary ovarian yolk sac carcinomas, omental metastases from one of these, and a primary retroperitoneal yolk sac carcinoma in a male are reported, as are the ultrastructural findings in human yolk sac from normal 7- and 12-week gestations. The most prominent feature of the tumors is the presence of voluminous basement membrane material (the nature of which is confirmed by indirect enzyme-labeled antibody technique in one case) in both intra-and extracellular location, corresponding to the PAS-positive hyaline globules seen in these tumors by light microscopy. The tumor cells are also demonstrated to produce this material in tussue culture. Although basement membrane has not been described previously in normal human yolk sac at 8 and 10 weeks' gestation, it was present in the 7-week specimen which we studied, suggesting that its production may be a feature of only very young sac. Other ultrastructural findings are also similar in human yolk sac carcinoma, normal human yolk sac, and rodent yolk sac and yolk sac carcinomas. Thus, these studies confirm the suggested germ cell-derived yolk sac origin of the human tumor.

The first case of ovarian sclerosing stromal tumor associated with endometrial adenocarcinoma in a 44-year-old woman is presented. By ultrastructural study, typical steroid-secreting type theca cells and various transitional tumor cells from fibroblast-like cells to theca-like cells were observed in the ovarian tumor. The clinical history of the patient and the ultrastructural study of this tumor suggested hormonal activity, but no apparent evidence of active hormone secretion was detected by plasma analysis for steroid hormones.

We report a population-based histopathologic review of primary ovarian neoplasms. No significant changes in incidence were encountered between the 1969 and 1979 review periods. The most frequent single tumor was benign cystic teratoma (26.5%), while the coelomic-derived "epithelial" tumors constituted the most frequent group (57.6% of all tumors and 93.8% of all malignant tumors). The high frequency of borderline tumors reported by others in nonpopulation-based material is confirmed, and the usual disseminated state of invasive carcinomas at the time of diagnosis is noted. Other data concerning incidence and bilaterality rates, patient ages, multiple primary malignancies, and problems in differential diagnosis and tumor grading are discussed.

Twenty cases of immature teratoma of the ovary with a neural component are analyzed. A plea is made for use of the nomenclature adopted from the new World Health Organization classification of ovarian tumors, the past confusion over terminology and histogenesis of this rare tumor is discussed. All the primary tumors in the present series contained at least some immature tissues (predominantly of neural origin) and were thus graded from 1 to 3 according to the criteria of Thurlbeck and Scully. No grade 0 tumors ("benign solid teratomas") were identified. We believe that thorough sectioning almost always insures the identification of immature elements. The prognosis was closely related to the histologic grade, but correlated poorly withthe clinical stage, the latter being influenced by the common finding (25 per cent of the cases in this series) of peritoneal implants composed exclusively of mature glial tissue, which is associated with a benign clinical evolution. This phenomenon of maturation or differentiation appears to be the rule rather than the exception in this tumor, since implants are usually of better or equal differentiation when compared with their primary tumors and older patients tend to have lower grade tumors than younger patients. Since the majority of patients with this tumor are young, primary surgical therapy should be conservative, unilateral salpingooophorectomy often being sufficient. Spontaneous or operative rupture of the tumor capsule carries an increased risk of subsequent dissemination. We have noted impressive clinical responses in patients with disseminated tumors of a high histologic grade after treatment with triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide) but do not recommend adjuvant therapy in patients with only grade 0 implants.

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.

Aromatase, 17 alpha-hydroxylase, and cholesterol side-chain cleavage P-450 cytochromes (P-450AROM, P-450(17 alpha,) and P-450SCC, respectively) were immunohistochemically localized in nine granulosa cell tumors, 15 thecomas, ten Sertoli-Leydig cell tumors, two steroid cell tumors, five fibromas, and five sclerosing stromal tumors. In the thecomas, P-450SCC and P-450(17 alpha) were positive in luteinized theca cells and in cells with vacuolated cytoplasm, while P-450AROM was not observed. In the steroid cell tumors, all the P-450 cytochromes were intensely stained. P-450SCC and P-450(17 alpha) were present in cells with vacuolated cytoplasm in two cases of sclerosing stromal tumor. P-450AROM was weakly demonstrated in one of the granulosa cell tumors. P-450(17 alpha,) P-450SCC, and P-450AROM were all faintly stained in the Sertoli-Leydig cell tumors. No P-450 cytochrome immunoreactivity was observed in any fibroma.

Immunohistochemical analysis of cytochromes P-450 aromatase and P-450 17 alpha-hydroxylase, which catalyze the production of estrogens and androgens, respectively, was performed for 23 cases of ovarian Brenner tumor. Immunoreactivity for P-450 aromatase was observed in the epithelial cells of the tumor distinctly in two cases and faintly in four cases, while immunoreactivity for P-450 17 alpha-hydroxylase was seen in two cases. No immunoreactivity was observed in the stromal cells of the tumors, nor were luteinized cells observed in the cases examined. No correlation was observed between the immunoreactivity of cytochromes P-450 in the epithelial cells of the tumor and endometrial abnormalities. These findings, together with a review of the literature, suggest that the usual Brenner tumor is not associated with specific steroidogenesis. Rare massive Brenner tumors may, however, be capable of androgenic or estrogenic activity.