The value of cell proliferation and angiogenesis in the prognostic assessment of ovarian granulosa cell tumors

Objectives: Most cases of granulosa cell tumors (GCT) of the ovary are char acterized by a relatively good outcome. However, some tumors behave aggress ively and some tend to recur many years after the initial diagnosis. Tumor growth depends on cell proliferation and angiogenesis. Thus, proliferative indices and microvessel density were studied to determine possible valuable methods to assess the GCT patient's outcome. Methods and study design: Paraffin-embedded tissue blocks were available fo r 60 patients with primary GCT and were investigated by immunostaining with monoclonal antibodies against PCNA, Ki-67 and factor VIII-related antigen. The follow-up was available for 51 patients and ranged from 25 to 206 mont hs. A clinical follow-up distribution of patients was made: 8 patients with recurrence (group I); 6 patients who lived with no evidence of recurrence for 100 months or more (group II), and 37 patients alive with no evidence o f recurrence in the follow-up period of less than 100 months (group III). Reslrlts: There was a statistical correlation between PCNA and Ki-67 prolif erative indices. A significant increase (P <0.05) of mean PCNA and Ki-67 pr oliferative indices and mean tumor size was seen in patients of Group I com pared to those of Group II. The mean PCNA proliferative index positively co rrelated with the mean Ki-67 proliferative index for Groups I and II. Mean microvessel density showed a positive correlation with mean PCNA and Ki-67 proliferative indices and with mean tumor size for Group I, whereas it was negatively correlated with PCNA proliferative index and tumor size for Grou p II. A positive correlation was found between mean mitotic count and both proliferative indices only for Group ii. The following features were indica tive of a relatively poor prognosis: GCT measuring >9 cm in diameter, PCNA >4.0%, Ki-67 >1.2%, and diffuse, insular and sarcomatoid histologic pattern s. Conclusions: The findings support the importance of proliferative factors, tumor size and histologic patterns as possible prognostic indicators for es timating the biologic behavior of patients with GCT. Unfortunately, angioge nesis did not seem to be a useful determinant parameter of a possible aggre ssive behavior. However, a longer follow-up period with larger series may b e required to assess the value of the parameters in prediction of patient s urvival.