Transitional Cell Tumors of the Ovary A Comparative Clinicopathologic, Immunohistochemical, and Molecular Genetic Analysis of Brenner Tumors and Transitional Cell Carcinomas

Transitional cell tumors of the ovary include 2 distinct clinicopathologic categories: Brenner tumors and transitional cell carcinomas (TCCs). Their molecular genetic alterations have not been fully investigated. We have performed a clinicopathologic, immunohistochemical. and Molecular genetic analysis of 19 transitional cell tumors including 13 Brenner tumors (5 benign, 7 borderline, and 1 malignant) and 6 TCCs. Immunoreactivity for epidermal growth factor receptor (EGFR), Ras. Cyclin D1, p16, Rb, and p53, as well as fluorescence in situ hybridization analysis for EGFR were assessed in all cases. Screening for mutations in K-Ras, B-Raf, CTNNB1, PIK3CA, and p53 genes was also performed. The mean patient age was 58 years (range, 32 to 85 y). Abdominal enlargement and pain were the usual complaints. Treatment was known in 14 patients: 10 had hysterectomy with bilateral salpingo-oophorectomy, which was accompanied by omentectomy in 7; and 4 had Only unilateral or bilateral salpingo-oophorectomy, 1 with omentectomy. Four patients had brachytherapy. Six borderline Brenner tumors were stage IA and 1 stage IIA. The malignant Brenner tumor was stage IA. One TCC was stage IA, one IC. 2 IIIC and the stage was unknown in 2 cases. Follow-up information was available only in 5 of the nonbenign cases. Two patients who had borderline Brenner tumors were alive and well at 3 and 10.9 years. The patient who had a malignant Brenner tumor died of pulmonary thromboembolism shortly postoperatively, and 2 patients with TCCs died of tumor 1.8 and 13 years, postoperatively. Brenner tumors and TCCs differed mainly in the expression of EGFR, p16, and p53. Benign Brenner tumors showed a low immunoexpression for all markers. Borderline Brenner tumors failed to immunoreact for p16, Rb. and p53 and showed weak immunostaining for Cyclin D1, moderate for Ras, and strong for EGFR. The malignant Brenner tumor was also negative for