TY - JOUR
T1 - Age-dependent morphological alterations of human ovaries from populations with and without BRCA mutations
AU - Qi Cai, Kathy
AU - Klein-Szanto, Andres
AU - Karthik, Devarajan
AU - Edelson, Mitchell
AU - Daly, Mary B.
AU - Ozols, Robert F.
AU - Lynch, Henry T.
AU - Godwin, Andrew K.
AU - Xu, Xiang Xi
PY - 2006/11
Y1 - 2006/11
N2 - Objective.: From analysis of pre-cancer ovarian tissues obtained from prophylactic oophorectomies, several studies reported the increased ovarian morphological changes in high-risk ovaries, but whether these morphological changes are associated with BRCA1/BRCA2 genotypes or are cancer precursors is controversial. Here, we have investigated a recent collection of ovaries from prophylactic oophorectomies and control ovaries from surgeries due to other non-ovarian-related cancer or non-neoplastic diseases to determine if ovarian morphological changes relate to BRCA1/2 genotypes or reproductive history. Methods.: We assembled a panel of archived ovarian tissues: 52 ovarian tissue blocks were from prophylactic oophorectomies of a high-risk (HR) population; 66 ovaries were from surgeries due to non-ovarian-related diseases, referred to as normal-risk (NR) group. The morphology of ovarian tissues was examined, and morphological changes including papillomatosis, invaginations, inclusion cysts, and epithelial stratification were assessed in a blinded fashion. Results.: No statistically significant difference in frequency of these histolopathologic features was found between HR and NR groups. However, inclusion cysts and deep invaginations were found much more commonly in women age 45-54 of either HR or NR groups. Conclusions.: This study suggests that no significant increase in the presence of non-neoplastic ovarian morphological changes is associated with BRCA1/BRCA2 mutations. Rather, the frequency of these histological features, especially inclusion cysts, may associate with age or menopausal status. We propose that ovulatory and perimenopausal gonadotropin stimulation produces ovarian morphological changes, and these histological features may promote the transformation of genetically compromised epithelial cells in the development of ovarian cancer.
AB - Objective.: From analysis of pre-cancer ovarian tissues obtained from prophylactic oophorectomies, several studies reported the increased ovarian morphological changes in high-risk ovaries, but whether these morphological changes are associated with BRCA1/BRCA2 genotypes or are cancer precursors is controversial. Here, we have investigated a recent collection of ovaries from prophylactic oophorectomies and control ovaries from surgeries due to other non-ovarian-related cancer or non-neoplastic diseases to determine if ovarian morphological changes relate to BRCA1/2 genotypes or reproductive history. Methods.: We assembled a panel of archived ovarian tissues: 52 ovarian tissue blocks were from prophylactic oophorectomies of a high-risk (HR) population; 66 ovaries were from surgeries due to non-ovarian-related diseases, referred to as normal-risk (NR) group. The morphology of ovarian tissues was examined, and morphological changes including papillomatosis, invaginations, inclusion cysts, and epithelial stratification were assessed in a blinded fashion. Results.: No statistically significant difference in frequency of these histolopathologic features was found between HR and NR groups. However, inclusion cysts and deep invaginations were found much more commonly in women age 45-54 of either HR or NR groups. Conclusions.: This study suggests that no significant increase in the presence of non-neoplastic ovarian morphological changes is associated with BRCA1/BRCA2 mutations. Rather, the frequency of these histological features, especially inclusion cysts, may associate with age or menopausal status. We propose that ovulatory and perimenopausal gonadotropin stimulation produces ovarian morphological changes, and these histological features may promote the transformation of genetically compromised epithelial cells in the development of ovarian cancer.
KW - Aging
KW - BRCA1/BRCA2
KW - Epithelium
KW - Etiological factor
KW - Menopause
KW - Ovarian cancer
KW - Ovulation
KW - Pre-malignant lesion
KW - Prophylactic oophorectomies
UR - http://www.scopus.com/inward/record.url?scp=33750144168&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000241759600061&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.ygyno.2006.03.053
DO - 10.1016/j.ygyno.2006.03.053
M3 - Article
C2 - 16698071
SN - 0090-8258
VL - 103
SP - 719
EP - 728
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -