Ovarian clear cell
carcinoma is found more often confined to the ovary (stage I) than high-grade serous
carcinoma. The
RHO GTPase family of
proteins is involved in
tumor invasion and
metastasis through regulation of the cytoskeleton. The expression of several RHO family genes, including RHOA, RHOC, CDC42, and 3 ARHGDIs (Rho
GDP dissociation inhibitors), was studied by real-time polymerase chain reaction in 22 clear cell
carcinomas and 31 high-grade serous
carcinomas. Immunoreaction for
p21-activated kinase 1 (a downstream effector of CDC42) was also investigated on 6 tissue microarrays containing 76
carcinomas (13 clear cell
carcinomas and 63 high-grade serous
carcinomas). Eight clear cell
carcinomas (8/21; 38%) were at stage I, whereas only 3 high-grade serous
carcinomas (3/31; 10%) were at stage I. Postoperatively, all patients were treated with
taxane and cisplatinum or carboplatinum. ARHGDIA
messenger RNA expression was higher in clear cell
carcinomas than high-grade serous
carcinomas (P = .07). In contrast, CDC42
messenger RNA levels were lower in clear cell
carcinomas than high-grade serous
carcinomas (P = .02). Immunoreaction for
p21-activated kinase 1 was concordant with the results obtained by real-time polymerase chain reaction for CDC42. In clear cell
carcinomas, RHOA and RHOC
messenger RNA expression was lower in stage I than in advanced-stage
tumors (P = .03 and P = .005, respectively). Furthermore, in high-grade serous
carcinomas, RHOA expression was higher in patients who did not respond to
chemotherapy (P = .04). ARHGDIA, CDC42, RHOA, and RHOC expression may contribute to explain the different stage at diagnosis of clear cell and high-grade serous
carcinomas. RHOA may cause resistance of high-grade serous
carcinoma to
chemotherapy.