Cultures of ovarian surface epithelium from women with and without a hereditary predisposition to develop female adnexal carcinoma.
OBJECTIVE
Conflicting evidence exists on whether in vivo morphological characteristics can distinguish Ovarian Surface Epithelium (OSE) of ovaries obtained from women with and without a predisposition to develop female adnexal (ovarian and fallopian tube) carcinoma. This study aims to detect differences in growth potential and morphology that are maintained or specifically expressed in vitro.


METHODS
Ovarian surfaces were scraped to retrieve OSE cells from 56 women at hereditary high risk for female adnexal carcinoma, of whom 33 are BRCA1 and four are BRCA2 mutation carriers (Predisposed OSE, POSE) and from 26 women without such risk (Non Predisposed OSE, NPOSE). Number of passages and total cell yield until last passage, as well as morphology was compared between both groups. To confirm morphology, the expression of epithelial, mesothelial, and fibroblast markers was assessed.


RESULTS
Both POSE and NPOSE cultures displayed similar growth potential and morphology. The expression of epithelial markers cyto-keratins 7 and 8 was similar between both groups. Only in cultures in which cells did not uniformly exhibit these markers, the percentage of cells expressing these markers was significantly lower at last passage when compared to the initial culture. In these latter cultures, cells that were morphologically indistinguishable from fibroblasts were observed. Mesothelial marker calretinin was expressed in 75% of cells of both POSE and NPOSE cultures and correlates with cyto-keratins 7 and 8 expression. CA 125 expression was equally low in POSE and NPOSE cultures (4.3%). Fibroblast markers FSM and vimentin were expressed in 100% and collagen IV was expressed in 16% of cells in all cultures.


CONCLUSIONS
OSE cells derived from women with a hereditary predisposition to develop female adnexal cancer possess similar in vitro characteristics as OSE from women without this predisposition. On basis of our results, it seems advisable to study only 100% cyto-keratins 7 and 8 positive OSE cultures, since contamination of fibroblasts in some primary OSE cultures cannot be ruled out.
Piek
Jurgen M J
JM
Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, The Netherlands.
Dorsman
Josephine C
JC
Shvarts
Avi
A
Ansink
Anca C
AC
Massuger
Leon F A G
LF
Scholten
Piet
P
van Diest
Paul J
PJ
Dijkstra
Jan C
JC
Weegenaar
Jitske
J
Kenemans
Peter
P
Verheijen
René H M
RH
D000290:Adnexa Uteri / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018394:CA-125 Antigen / Q000096:biosynthesis; D064032:Calbindin 2; D018929:Cell Culture Techniques; D024141:Collagen Type IV / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D053552:Keratin-7; D007633:Keratins / Q000096:biosynthesis; D008875:Middle Aged; D009154:Mutation; D010053:Ovary / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C576764:CALB2 protein, human; D064032:Calbindin 2; D024141:Collagen Type IV; C507497:KRT7 protein, human; D053552:Keratin-7; D064030:S100 Calcium Binding Protein G; D007633:Keratins