Expression of differentiation and proliferation related proteins in epithelium of prophylactically removed ovaries from women with a hereditary female adnexal cancer predisposition.
OBJECTIVE
To investigate the occurrence of preinvasive neoplastic lesions in ovarian surface epithelium and ovarian inclusion cyst epithelium of women with a hereditary predisposition to the development of female adnexal (ovarian and fallopian tube) carcinoma and to assess the expression of differentiation and proliferation related proteins within putative sites of origin of serous ovarian carcinoma, the ovarian surface epithelium and ovarian inclusion cyst epithelium.


METHODS
Twenty-one ovaries, prophylactically removed from 11 women predisposed to the development of female adnexal cancer (cases) were compared with 22 ovaries from 11 women without such predisposition (controls). Archival histological specimens were screened for hyperplastic and dysplastic epithelial lesions. In both the ovarian surface and inclusion cyst epithelia, the percentage of cells was determined that stained positively for Ki67, p21, p27, p53, cyclin A, cyclin D1, bcl-2 and the presence of HER-2/neu, oestrogen (ER-alpha) and progesterone receptors (PR).


RESULTS
No preinvasive neoplastic lesions were detected. However, hyperplastic areas were found in three cases and in four controls (NS). ER-alpha (P = 0.013), PR (P < 0.001), bcl-2 (P = 0.008), p21 (P = 0.046) and p27 (P = 0.008) were expressed in a significantly higher percentage of cells in inclusion cyst epithelium than in ovarian surface epithelium (both groups). The latter showed higher bcl-2 expression in cases (P = 0.05) compared with controls. The inclusion cyst epithelium of cases showed higher expression of bcl-2 (P = 0.006) and PR (P = 0.039) compared with controls. Proliferation was low in both cases and controls as reflected by low Ki67 expression. Over-expression of p53, cyclin D1 and HER-2/neu was not detected.


CONCLUSIONS
Premalignant changes are not a common feature of ovaries removed prophylactically from women predisposed to the development of female adnexal carcinoma. Increased expression of p21, p27, and ER-alpha is seen in inclusion cyst compared with ovarian surface epithelium of women with and without an inherited risk of adnexal carcinoma. This is most probably caused by the different intraovarian hormonal milieu of inclusion cyst epithelium. However, the increased expression of bcl-2 and PR in the inclusion cyst epithelium of patients with a hereditary predisposition may reflect early disruption of hormonal balance and growth control.
Piek
J M J
JM
Department of Obstetrics and Gynaecology, VU University Medical Centre, 1007 MB Amsterdam, the Netherlands.
Verheijen
R H M
RH
Menko
F H
FH
Jongsma
A P M
AP
Weegenaar
J
J
Gille
J J P
JJ
Pals
G
G
Kenemans
P
P
van Diest
P J
PJ
D000291:Adnexal Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005187:Fallopian Tubes / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010052:Ovariectomy; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins