Clinicopathological features and immunoprofile of 30 cases of Brenner ovarian tumors.

AIM: The aim of this study was to investigate the clinicopathological and immunopathological features of Brenner ovarian tumors. MATERIALS AND METHODS: Thirty cases of Brenner ovarian tumors were examined in our laboratory among 1,680 cases of ovarian tumors, representing 1.5% of all tumors examined. Blocks of paraffin-embedded tumor tissue for all cases were available for additional immunohistochemical stain by a Ventana autoimmunostainer. Moreover, antibodies for Uroplakine III (cellmarque AU-1 clone, 1:25) Chromogen (monosan clone 5H7,1:25) WT1 (novocastra, clone 3F-H2, 1:25) NSE (DAKO, clone BB5/NC/V1-H14, 1:50), CK20 (DAKO, clone Ks20.8, 1:50),CK7 (Zymed 1:25, clone V-TL12/30)were used. RESULTS: The mean age of the patients was 51.4 years ranging from 16 to 82 years. The tumor was unilateral in 28 cases (16/28 in the right ovary and 12/28 in the left ovary) and bilateral in two cases. Twenty-eight cases (93%) were benign and two (7%) were proliferating (borderline) tumors. Seventeen cases (56%) were pure Brenner tumors, measuring from 0.5 to 2.5 cm and 13 cases (44%) were mixed tumors consisting of a Brenner tumor element and a mucinous ovarian tumor (10/13 cases, 53.8%) and a germ cell tumor in 3/13 cases. The largest diameter of the mixed tumors ranged from 7 to 22 cm. The largest area consisting of Brenner elements measured 7 cm. The immunoprofile of Brenner tumor cell was cytokeratine-7 positive (30/30 cases) cytokeratine-20 negative in the Brenner cell element but positive in the mucinous component in 5/7 cases of mixed Brenner tumors, focally WT-1 positive (5/30 cases), NSE negative (0/30 cases) and focally chromogranine positive (6/30 cases), Uroplakin-III positive in 23/30 cases, with faint cytoplasmatic or luminal distribution. In conclusion, Brenner ovarian tumors are unilateral, small and benign neoplasms in their majority and present specific histopathological and immunopathological characteristics and mixed forms with other epithelial and germ cell neoplasms. This could be explained as a form of metaplasia or a diverse histogenesis from surface epithelium and/or the germ cell ovarian component.

Transitional cell neoplasms of the ovary and urinary bladder: a comparative immunohistochemical analysis.

Walthard cell nests, the Brenner tumor (benign, proliferating, low malignant potential, and malignant), and primary ovarian transitional cell carcinoma are considered to be primary female genital tract proliferations of transitional-type (urothelial) epithelium on conventional light microscopic grounds. In order to further investigate the similarities (or dissimilarities) of proliferations of female genital tract transitional epithelium and urothelium, we compared transitional cell proliferations (TCPs) of the female genital tract (n = 25) and urinary bladder (n = 15) using antibodies to carcinoembryonic antigen (CEA; clone 0062), carbohydrate determinant 19-9 (CA19-9; clone 1116-NS-19-9), cytokeratin 7 (CK-7; clone OV-TL 12/30), and cytokeratin 20 (CK-20; clone Ks 20.8), four monoclonal antibodies that have been shown to stain transitional cell urothelial proliferations. Both groups of tumors exhibited significant staining for CEA, CA19-9, and CK-7, and the difference in numbers of cases staining was not significant. CA19-9 was present in 15 of 25 female genital tract TCPs as compared with 12 of 15 bladder TCPs; CEA was present in 17 of 25 female genital tract TCPs and nine of 15 comparable bladder TCPs. CK-7 was present in all cases studied with the exception of one Walthard cell nest and a malignant Brenner tumor that was not immunoreactive with the other antibodies tested. In contrast, 13 of 15 bladder TCPs were CK-20 positive, whereas only one of 25 female genital tract TCPs was positive (< 5% of cells). Walthard cell nests and benign Brenner tumors were more likely to be CA19-9 positive than were Brenner tumors of low malignant potential, malignant Brenner tumors, and primary transitional cell carcinoma of the ovary. We conclude that despite their apparent morphologic and immunologic similarity to TCPs of the urinary bladder (particularly at the histologically low-grade end of the transitional cells spectrum), Walthard cell nests and ovarian Brenner tumors constitute an immunophenotypically distinct form of TCP.

Epithelial antigens in carcinomas of the ovaries. Relation to histological classification.

In an attempt to assess and improve the histological classification of ovarian tumors the value of immunohistochemical techniques has been examined in 50 ovarian tumors. A panel of six immunohistochemical markers (two cytokeratins, EP4, EMA, CEA, and vimentin) seems to have no additional value in differential diagnosis and typing of ovarian tumors.

Serum CA 125 concentrations in patients with benign ovarian tumours.

Serum CA 125 concentrations have been measured in 115 patients with histologically confirmed nonmalignant pelvic disease, that is, serous cystadenoma (n = 56), mucinous cystadenoma (n = 14), fibroma (n = 33), thecoma (n = 8), and Brenner tumour (n = 4). Increased CA 125 concentrations (> 35 KU/L) were found in 14 patients, with a range of 46-891 KU/L, a mean of 205 KU/L, and a median of 97 KU/L. The highest values were found in patients with ascites. Serial measurements in one patient showed a fall in the 2 days immediately after surgery, over the next 3 days showing a two- to three-fold increase, followed by a slow return to normal over the next 7 weeks. Elevated CA 125 levels may not indicate ovarian malignancy and do not differentiate between benign and malignant pelvic masses.

An investigation of NCRC11 immunoreactivity in normal and neoplastic epithelia of the female genital tract and ovary.

NCRC11 is a monoclonal antibody raised against human mammary carcinoma cells. The prognostic value of tumour cell immunoreactivity to NCRC11 in breast cancer has been shown previously. This study describes NCRC11 immunoreactivity in a wide range of normal and neoplastic epithelial types from the female genital tract and ovary. In the tumours examined, a wide range of staining patterns was seen. The implications of these findings are discussed in relation to the potential uses of this antibody in diagnosis and monitoring of gynaecological diseases.

Malignant Brenner tumor with peritoneal metastasis.

A case of malignant Brenner tumor with peritoneal metastasis in a 67-year-old woman was reported. The multilocular cystic tumor of right ovary was 420 g in weight, and their cystic walls were covered with multilayered tumor cells showing papillary pattern very frequently. The tumor was histologically transitional cell carcinoma with occasional glandular structures but no squamous differentiation corresponding to grade 2 or 3 urinary bladder carcinoma. The pattern of benign Brenner tumor was not identified, but there was some area of proliferating Brenner tumor. Immunohistochemically, carcinoembryonic antigen was detected in several tumor cells, especially in the intercellular spaces among them, and cytokeratin was detected only in some tumor cells. Ultrastructurally, the malignant Brenner tumor shared many common features with the benign one and also bladder tumor. Intercellular spaces with microvilli were frequently found and thought to be important for diagnosis. The morphologic criteria of this rare tumor are discussed.

Lacto-N-fucopentaose III activity in the serum of patients with ovarian carcinoma.

The expression of the lacto-N-fucopentaose III (LNF III) epitope by tumor cells of the gastrointestinal tract and ovary has been observed in tissue sections with the use of the murine monoclonal antibody GA 29-1. The presence of the LNF III epitope in the circulation of patients with colorectal cancer has also been reported. In this preliminary study, we describe the presence of LNF III activity in the serum of patients with adenocarcinoma of the ovary. Twelve of 18 (66%) patients with stage I-IV disease demonstrated high reactivity to the GA 29-1 monoclonal antibody. This serum reactivity was independent of disease stage and histologic cell type. In contrast, only 1 of 6 control patients demonstrated a false-positive level of reactivity to GA 29-1. These preliminary results suggest that LNF III warrants further study of its potential application as a serum tumor marker test in patients with adenocarcinoma of the ovary.

The sebaceous gland antigen defined by the OM-1 monoclonal antibody is expressed at high density on the surface of ovarian carcinoma cells.

A monoclonal antibody, designated OM-1, was raised against ovarian serous papillary cystadenocarcinoma (stage IV) cells. This antibody was found to react strongly with primary and metastatic ovarian serous cystadenocarcinomas and endometrioid carcinomas but the antigen detected was either absent or at very low levels in ovarian mucinous adenocarcinomas, clear cell carcinomas, benign serous and mucinous cystadenomas and Brenner tumours. The OM-1 antibody gave no detectable reaction with 93 other human tumours, including examples of breast and colon adenocarcinomas. In normal tissues the OM-1 antibody reacted with normal sebaceous gland cells, lung type II pneumocytes and placental syncytial trophoblasts. In the normal ovary OM-1 reactivity was confined to extremely weak staining of the surface epithelium. No reaction with any other ovarian cell type could be detected. No evidence of reaction with other normal cell populations present in 24 adult and seven foetal tissues was found. The antigen detected is compared with other ovarian tumour-associated antigens. The OM-1 antibody is likely to prove of value in the detection and diagnosis of ovarian carcinoma.

Tumor and serum CEA content in gynecologic neoplasms.

The relationship of serum carcinoembryonic antigen (CEA) levels to tumor tissue CEA content, and tumor weight in patients with different genital tract neoplasms was studied. Two-step extraction of tumor tissues was performed using perchloric acid and 3 M KCl. Sera and tissue extracts were assayed for CEA content by double-antibody radioimmunoassay. No clear correlation was found between serum CEA and tumor CEA contents, tumor weight, and histological structure. Our results showed, however, that high CEA concentrations in tumor tissue (10 micrograms/g or higher) were accompanied by elevated values in plasma.

Histogenesis of Brenner tumors, II: histochemistry and CEA.

The histochemical characteristics of 21 benign Brenner tumors were studied. The mucins associated with these tumors are of transitional cell origin and do not represent a secondary metaplasia of transitional to intestinal-type epithelium. The goblet and ciliated columnar cells associated with the proliferative Brenner tumor are thought to represent a parallel mucinous metaplasia from celomic epithelium. Thirteen of the 16 benign Brenner tumors and the one proliferative Brenner tumor were found to contain carcinoembyronic antigen (CEA), indicating an additional antigenic similarity to transitional epithelium.