COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Abstract

Objectives: Uterine carcinosarcomas are uncommon, highly aggressive neoplasms that frequently recur after surgical treatment and adjuvant chemo-radiotherapy. Patients with recurrent disease respond poorly to salvage chemotherapy and irradiation. New therapeutic options are required for patients with metastatic disease. Clinical evidences showing the effect of a tyrosine kinase inhibitor, STI571, in c-KIT-positive gastrointestinal tumors, the role of COX-inhibitors chemotherapy-associated in colorectal cancer patients and the successful therapeutic possibility of anti-HER2 therapy in metastatic breast carcinoma, have encouraged us to study the expression of c-KIT, COX-2 and HER-2/neu in uterine carcinosarcomas.

Methods: We analyzed the expression of COX-2, c-KIT and HER-2/neu in 24 uterine carcinosarcomas and their correlation with clinical outcome. Disease-free interval and actuarial survival rates were the end points of the study.

Results: High staining intensity for COX-2 was observed in 8 cases (33.3%). C-KIT was expressed in 4 cases (16.7%) and HER-2/neu in 7 cases (29.2%). Patients with COX-2-positive tumors had a significantly poorer disease-free interval and survival (P = 0.01 and P = 0.05, respectively). All patients with c-KIT-positive tumors had early stage disease. In spite of this, their survival was not significantly better than that of c-KIT-negative cases. HER-2/neu expression did not show any correlation with clinical outcome.

Conclusion: c-KIT, COX-2, and HER-2/neu were expressed in different proportions of uterine carcinosarcomas. COX-2 expression was a strong indicator of unfavorable prognosis. These results warrant further study to evaluate the possible role of a new molecularly targeted cancer therapy with COX-2 inhibitors in patients with uterine carcinosarcomas. The role of c-KIT expression and consequently the hypothetical use of STI571 should be tested in a larger series.