Pathologic Findings in Prophylactic Oophorectomy Specimens in High-Risk Women

Leeper, K.R.; Garcia, Rochelle L.; Swisher, Elizabeth M.; Goff, Barbara A.; Greer, Benjamin E.; Paley, Pamela J.

doi:10.1006/gyno.2002.6779

Cited by 280 publications

(149 citation statements)

References 15 publications

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“…Although papillary serous carcinoma occurs more often in the ovary than in fallopian tubes clinically, the early premalignant lesions were more frequently identified in the fallopian tubes. [31][32][33] It is proposed that the fallopian tube, particularly the fimbria, is the most common location for early serous carcinoma. 34 In the present study, we demonstrated that a significant number (67%) of ovarian PSC were focally or diffusely positive for PAX2 and that PAX2 was detected in fallopian tubes and secondary Mü llerian structures in the ovary, but not in the ovarian surface epithelium or inclusion cysts.…”

Section: Discussionmentioning

confidence: 99%

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

et al. 2007

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PAX2 is a urogenital developmental transcription factor expressed in the Wolffian ducts, developing kidneys, and Mü llerian ducts during embryonic stage. Its function in renal development is well documented and its clinical application in the diagnosis of lesions of renal origin has been reported recently. However, information on its role in the Mü llerian-derived genital tract is sparse. In this study, we investigated the expression of PAX2 in human female genital tract using immunohistochemistry. We demonstrated that PAX2 was expressed specifically in the epithelial cells of fallopian tube, endometrial and endocervical glands, but not in the stromal tissues in these areas. PAX2 was detected in secondary Mü llerian structures in the ovary, such as endometriotic and endosalpingiotic glands and rete ovarii, but not in ovarian surface epithelium, surface epithelium-derived inclusion cysts, stroma, or sex-cord-derived structures such as follicles, oocytes, and corpus luteum. In addition, PAX2 was detected in 67% of ovarian papillary serous carcinomas (N ¼ 36) but rarely in peritoneal malignant mesotheliomas, with two exceptions (N ¼ 54). Interestingly, the two PAX2-positive 'peritoneal malignant mesotheliomas' were from female patients and were positive for estrogen receptor. The significance of expression of PAX2 and estrogen receptor in these cases is under investigation. Taken together, we suggest that PAX2 is a novel Mü llerian-specific epithelial marker when used in proper clinical settings. Identification of PAX2 in the majority of papillary serous carcinomas of the ovary but not in the ovarian surface epithelium or epithelium-derived inclusion cysts suggests that this malignant epithelial tumor may be directly derived from the primary or secondary Mü llerian epithelium in or surrounding the ovary, rather than from the surface epithelium or its derivatives.

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Section: Discussionmentioning

confidence: 99%

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

et al. 2007

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“…Previous studies have reported that FTC show an aneuploid DNA content, overexpression of TP53, ERBB2 and CMYC (Hellstro¨m et al, 1994;Chung et al, 2000), as well as a high frequency of KRAS mutations (Mizuuchi et al, 1995). Deficiency for BRCA1 may also contribute to the genesis of FTC, since the incidence of FTC is higher in families carrying BRCA1 mutations (Zweemer et al, 2000;Aziz et al, 2001;Leeper et al, 2002) and dysplasia is a frequent finding in prophylactically removed Fallopian tubes from BRCA1 carriers (Piek et al, 2001). However, the application of chromosome comparative genomic hybridization (CGH) to the study of FTC revealed that these tumors are characterized by a high level of copy number aberrations with frequent amplification of 3q (Heselmeyer et al, 1998;Pere et al, 1998).…”

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confidence: 98%

Genome-wide-array-based comparative genomic hybridization reveals genetic homogeneity and frequent copy number increases encompassing CCNE1 in Fallopian tube carcinoma

et al. 2003

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“…[9][10][11] Although the identification of serous cancer precursor lesions in the ovary has been elusive, we and others have documented occult carcinomas in the ovaries and fallopian tubes of women with BRCA1 or BRCA2 mutations undergoing prophylactic surgery, with a significant proportion of these early cancers present in the fallopian tube and not the ovary. [12][13][14][15] Fallopian tube epithelium in the premenopausal woman frequently shows some degree of epithelial proliferation, a finding considered to be within normal limits. 16 Reports describing abnormalities of the tubal epithelium have used various terminologies, including dysplasia, atypical hyperplasia, and mucosal epithelial proliferations, but until recently, there has been no attempt at defining a serous cancer precursor within tubal mucosa.…”

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confidence: 99%

Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers

et al. 2009

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Occult invasive and intraepithelial carcinomas have been identified in the tubal fimbria of BRCA mutation carriers undergoing prophylactic surgery, and recently described lesions overexpressing p53 in the distal tubes of mutation carriers, and non-carriers, have been proposed as histological precursors of high-grade serous carcinoma. The aim of this study was to confirm these findings in a larger, independent case set, to further characterize the cancer precursor lesions, and to determine their frequency in BRCA mutation-positive (n ¼ 176) and control groups (n ¼ 64). For the purposes of this study, we excluded cases without documentation of a germline mutation of BRCA1/2, and without histological examination of the entire tube, and cases with a diagnosis of invasive carcinoma. Controls included salpingectomies from women undergoing surgery for reasons other than ovarian malignancy. Diagnostic categories were assigned based on combined histological review and immunostaining results. Histological abnormalities were identified in 23% of the BRCA group and in 25% of the control group, and included localized p53 overexpression in 20% of the BRCA group and 25% of the control group. Tubal intramucosal carcinoma was identified in 8% of the BRCA cases and in 3% of the control group. Four cases of intraepithelial carcinoma (21%) did not overexpress p53. There was no significant difference in the median age, frequency of histological abnormalities, p53 signatures, or tubal intraepithelial carcinoma between the BRCA mutation-positive and control groups. This large, blinded review of tubes from BRCA mutation carriers confirms previous reports of putative cancer precursors in distal tubal mucosa, and that p53 signatures occur with similar frequency in women at low and high genetic risk of tubal/ovarian carcinoma. Tubal intraepithelial carcinoma, which, like invasive serous cancer, usually but not always overexpresses p53 protein, is more frequent in BRCA mutation carriers.

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Pathologic Findings in Prophylactic Oophorectomy Specimens in High-Risk Women

Cited by 280 publications

References 15 publications

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

Genome-wide-array-based comparative genomic hybridization reveals genetic homogeneity and frequent copy number increases encompassing CCNE1 in Fallopian tube carcinoma

Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers

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