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Cell proliferation and apoptosis in BRCA-associated hereditary ovarian cancer
Douglas A Levine1, Mark G Federici, Victor E Reuter
1Gynecology and Breast Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Objective:
The goal was to test the hypothesis that cellular growth properties differ between hereditary and sporadic ovarian cancers.
Methods:
Cell proliferation and apoptosis were assessed in 67 tumors associated with deleterious germline BRCA mutations (hereditary) and 69 tumors without BRCA mutations (sporadic). Cell proliferation was evaluated by immunohistochemical analysis of Ki-67 expression, and apoptosis was assessed using a TUNEL assay.
Results:
The mean number of Ki-67-immunopositive nuclei was significantly higher in ovarian cancers from the hereditary group compared with those from the sporadic group (P = 0.017). Cell proliferation did not differ significantly between BRCA1- and BRCA2-associated hereditary tumors, and apoptosis did not differ significantly between the hereditary and sporadic tumors.
Conclusion:
These data indicate that ovarian carcinomas associated with germline BRCA mutations have a significantly higher growth fraction than sporadic cancers. This property may contribute to an improved response to cytotoxic chemotherapy, partially accounting for the longer recurrence-free interval and overall survival observed in the hereditary group.