Ovarian dysplasia in prophylactic oophorectomy specimens

BACKGROUND The authors suggested that the loss of collagen IV and laminin‐containing basement membrane and the loss of Disabled‐2 (Dab2) expression were two critical events associated with morphologic dysplastic changes of the ovarian surface epithelium as a step in tumorigenicity. Both the basement membrane and Dab2, a candidate tumor suppressor of ovarian carcinoma, were involved in epithelial cell surface positioning and organization. The authors speculated that the purging of the basement membrane may be similar to the proteolysis during gonadotropin‐stimulated ovulation, a cyclooxygenase 2 (Cox‐2)‐mediated process. METHODS Prophylactic oophorectomy is used to prevent breast and ovarian carcinoma in high‐risk populations. These ovarian tissue specimens often contain an increased presence of morphologically abnormal lesions that are believed to be preneoplastic. The authors evaluated archived prophylactic oophorectomy specimens to verify whether the loss of Dab2 expression and the removal of the basement membrane that occur at the ovarian surface and inclusion cyst epithelia are molecular markers of preneoplastic lesions. Of the 36 samples containing identifiable ovarian surface epithelial components on slides, immunostaining was employed to evaluate the intactness of the basement membrane (periodic acid–Schiff [PAS], collagen IV, and laminin) and the expression of Dab2 and Cox‐2. Expression of Cox‐1 and Cox‐2 also were evaluated in cultured ovarian surface epithelial cells prepared from ovarian tissue specimens removed from patients who underwent prophylactic surgery. RESULTS The morphologically normal ovarian surface epithelium typically contained a collagen IV‐ and laminin‐positive basement membrane, which also was detected by PAS staining. Many morphologically altered areas, such as papillomatosis, invaginations, inclusion cysts, stratification, adenomas, and microscopic adenocarcinomas, were found in these specimens. Both the morphologically altered and adjacent morphologically normal epithelia consistently exhibited loss of basement membrane and/or Dab2 expression and an increase in Cox‐2 staining. Frequently, an increase in Cox‐2 staining was correlated with the loss of epithelial basement membrane in morphologically normal areas. CONCLUSIONS The loss of Dab2 and basement membrane and the overexpression of Cox‐2 were observed in presumptive neoplastic precursor areas of oophorectomy specimens obtained from a population at high risk for ovarian carcinoma. Transient loss of collagen IV and laminin in the basement membrane of the preneoplastic epithelium and the loss of Dab2 expression are common early events associated with morphologic alteration and tumorigenicity of the ovarian surface epithelium. The authors concluded that Cox‐2 overexpression may play a role in the purging of basement membrane of the ovarian surface epithelium, mimicking the process of ovulation. Further experiments may be able to test the hypothetical model derived from these histologic observations. Cancer 2003;98:2607–23. ...

Section: Resultssupporting

confidence: 87%

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confidence: 99%

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confidence: 99%

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Loss of surface and cyst epithelial basement membranes and preneoplastic morphologic changes in prophylactic oophorectomies

Roland

Yang

et al. 2003

“…The macroscopic appearance of the removed ovaries usually is unremarkable. Thorough histologic examination of entirely submitted ovaries, however, may yield a number of structural changes, as reported in microscopic descriptions4–8 and computerized image analyses 9–12. For some of these changes, the terms ovarian dysplasia or ovarian intraepithelial neoplasia have been proposed,4, 5 suggesting that they may represent precursor lesions of invasive ovarian carcinoma.…”

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confidence: 99%

Prophylactic oophorectomy

Schlosshauer

Cohen

Penault‐Llorca

et al. 2003

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BACKGROUND The tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia‐associated markers in prophylactically removed ovaries, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium. METHODS Morphologic features and immunohistochemical expression patterns of CA‐125, Ki‐67, p53, E‐cadherin, and Bcl‐2 were evaluated in 21 normal ovaries, 31 ovaries that were removed prophylactically for increased carcinoma risk, and 7 ovarian papillary serous carcinomas. Representative slides from formalin‐fixed, paraffin‐embedded tissue blocks were submitted to immunohistochemical staining and were evaluated independently by three gynecologic pathologists. For statistical analyses, Fisher exact tests, multivariate analyses, Spearman rank correlation coefficients, Wald statistics, Kruskal–Wallis tests, and Mann–Whitney tests were used. Immunohistochemical staining results were correlated with morphologic findings. RESULTS The authors found progressive increases in reactivity with the lowest expression in normal ovarian epithelium, stronger expression in epithelium from prophylactically removed ovaries, and the highest expression in carcinomas for Ki‐67 and p53. A similar trend was observed for CA‐125. Positivity for Ki‐67 and p53 was seen predominantly in the epithelium of inclusion cysts and deep invaginations, including those areas that had been identified as hyperplastic or dysplastic on routine hematoxylin and eosin‐stained sections. CONCLUSIONS The current results suggest biologic/molecular evidence for the existence of preneoplastic changes in ovarian surface epithelium and support the previously proposed concept of ovarian dysplasia. Subtle morphologic alterations of the ovarian epithelium may be biologically significant. Cancer 2003;98:2599–606. © 2003 American Cancer Society.

“…The frequencies of several types of morphologic alterations, including epithelial pseudostratification, papillomatosis, cortical invagination, inclusion cysts, and stromal hyperplasia, were shown to be significantly higher in the cancer‐prone ovaries than in control tissues. However, of two similar studies, one failed to document morphologic differences in ovaries from BRCA heterozygotes compared with control ovarian tissues,16 whereas another found ovarian dysplasia to be more common in ovaries from BRCA heterozygotes than from controls 17…”

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confidence: 99%

Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens fromBRCA1 heterozygotes

Barakat

Federici

Saigo

et al. 2000

BACKGROUND The high mortality associated with ovarian carcinoma is largely a reflection of the inability to diagnose the disease at an early stage; the identification of a histologic lesion or molecular marker associated early stages of transformation would represent an important advance in understanding the natural history of this cancer. The existence of individuals with germline mutations in the ovarian and breast carcinoma susceptibility gene BRCA1 represents a unique opportunity to search for such premalignant alterations in ovarian tissues that are at unusually high risk for tumorigenesis. In this study, the authors addressed the hypothesis that pathologically normal ovaries removed from BRCA1 heterozygotes are likely to display premalignant histologic, molecular, and/or cell biologic alterations that may provide insight into early stages of ovarian tumorigenesis. METHODS Ovarian tissues from 18 BRCA1 heterozygotes and from 20 age‐matched controls were examined in a blinded fashion for histologic evidence of surface epithelial pseudostratification, epithelial inclusion cysts, deep cortical invaginations of surface epithelium, increased stromal cell activity, and surface papillomatosis. Immunohistochemical analyses for expression of BRCA1, p53, and ERBB‐2 and quantitation of cell proliferation (Ki‐67 expression) and apoptosis (TUNEL assay), were also performed on all specimens. RESULTS Although histologic alterations were observed, there was no difference in frequency between cases and controls. Analysis of BRCA1 expression revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of all ovaries. Similarly, no evidence was found of p53 overexpression in any ovarian tissue or of a difference in ERBB‐2 expression between cases and controls. Finally, no differences were observed in epithelial cell proliferation or apoptosis. CONCLUSIONS Clinically, normal ovaries from BRCA1 heterozygotes do not show evidence of premalignant alterations in histology, molecular markers, cell proliferation, or apoptosis, indicating that such changes are likely rare. Cancer 2000;89:383–90. © 2000 American Cancer Society.