Raspollini Maria Rosaria, Susini Tommaso, Amunni Gianni, Paglierani Milena, Taddei Antonio, Marchionni Mauro, Scarselli Gianfranco, Taddei Gian Luigi
Department of Human Pathology and Oncology, University of Florence, School of Medicine, 85, 50134 Florence, Italy.
Gynecol Oncol. 2005 Jan;96(1):159-67. doi: 10.1016/j.ygyno.2004.09.050.
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.
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.
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.
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.
子宫癌肉瘤较为罕见，是侵袭性很强的肿瘤，手术治疗及辅助放化疗后常复发。复发患者对挽救性化疗和放疗反应欠佳。转移性疾病患者需要新的治疗选择。有临床证据表明酪氨酸激酶抑制剂STI571对c-KIT阳性胃肠道肿瘤有效，环氧化酶（COX）抑制剂在结直肠癌患者化疗中的作用以及抗HER2治疗在转移性乳腺癌中的成功治疗可能性，促使我们研究c-KIT、COX-2和HER-2/neu在子宫癌肉瘤中的表达情况。
我们分析了24例子宫癌肉瘤中COX-2、c-KIT和HER-2/neu的表达及其与临床结局的相关性。无病生存期和精算生存率为研究终点。
8例（33.3%）观察到COX-2高染色强度。4例（16.7%）表达c-KIT，7例（29.2%）表达HER-2/neu。COX-2阳性肿瘤患者的无病生存期和生存率显著较差（分别为P = 0.01和P = 0.05）。所有c-KIT阳性肿瘤患者均为早期疾病。尽管如此，其生存率并不显著优于c-KIT阴性病例。HER-2/neu表达与临床结局无任何相关性。
c-KIT、COX-2和HER-2/neu在不同比例的子宫癌肉瘤中表达。COX-2表达是预后不良的有力指标。这些结果值得进一步研究，以评估COX-2抑制剂这种新的分子靶向癌症治疗方法在子宫癌肉瘤患者中的可能作用。c-KIT表达的作用以及因此假设使用STI571应在更大系列中进行测试。
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