COX-2, c-KIT and HER-2/neu expression in uterine carcino sarcomas: prognostic factors or potential markers for targeted therapies?
COX-2, c-KIT and HER-2/neu expression in uterine carcino sarcomas: prognostic factors or potential markers for targeted therapies?
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DOI：
10.1016/j.ygyno.2004.09.050
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Taddei, GL
中科院分区：
文献类型：
--
作者：
Raspollini, MR;Susini, T;Taddei, GL
目标。子宫癌肉瘤是一种罕见的高侵袭性肿瘤，在手术治疗和辅助化疗后经常复发。复发性疾病患者对补救性化疗和放疗反应较差。转移性疾病患者需要新的治疗选择。临床证据显示酪氨酸激酶抑制剂STI571在c-KIT阳性胃肠道肿瘤中的作用，cox -抑制剂在结直肠癌化疗相关患者中的作用以及抗her2治疗转移性乳腺癌的成功治疗可能性，鼓励我们研究c-KIT， COX-2和HER-2/neu在子宫癌肉瘤中的表达。我们分析了COX-2、c-KIT和HER-2/neu在24例子宫癌肉瘤中的表达及其与临床预后的关系。无病间期和精算生存率是研究的终点。COX-2高染色8例（33.3%）。C-KIT表达4例（16.7%），HER-2/neu表达7例（29.2%）。cox -2阳性肿瘤患者的无病间期和生存期明显较差（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，他们的生存并没有明显优于c- kit阴性病例。HER-2/neu的表达与临床预后无相关性。c-KIT、COX-2、HER-2/neu在子宫癌肉瘤中表达比例不同。COX-2表达是不良预后的有力指标。这些结果值得进一步研究，以评估COX-2抑制剂在子宫癌肉瘤患者中新的分子靶向癌症治疗的可能作用。c-KIT表达的作用以及因此假设的STI571的使用应该在更大的系列中进行测试。(C) 2004爱思唯尔公司版权所有。
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. (C) 2004 Elsevier Inc. All rights reserved.