Tangjitgamol Siriwan, Kittisiam Thannaporn, Tanvanich Sujitra
1 Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
2 Department of Anatomical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
Tumour Biol. 2017 Sep;39(9):1010428317725834. doi: 10.1177/1010428317725834.
The study was to evaluate the prevalence of mismatch repair gene defect among Thai patients with endometrial cancer and its association with clinico-pathological features and survivals. The formalin fixed paraffin-embedded blocks of EMC tissue from hysterectomy specimens of patients having surgery in our institution between 1 Jan 1995 and 31 December 2016 were assessed for the immunohistochemical expression of 4 mismatch repair proteins (MLH1, PMS, MSH2, MSH 6). Mismatch repair gene defect was determined by a negative expression of at least 1 protein. Among 385 EMC patients included in the study, mean age was 57.3 ± 10.8 years with 62.3% aged ⩽ 60 years. The most frequent mismatch repair gene defect was MSH6 (38.7%), followed by PMS2 (34.3%), MLH1 (33.2%), and MSH2 (16.4%). Overall, 55.1% showed negative expression of at least one protein. We found significantly higher mismatch repair gene defect in patients aged ⩽ 60 years, with early stage disease, and negative lymph node status than the other comparative groups: 59.2% vs 48.3% for age (p = 0.037), 58.2% vs 45.2% (p = 0.027) for stage, and 58.1% vs 44.6% (p = 0.048) for nodal status. The 5-year progression-free survival, overall survival, and endometrial cancer-specific survival of patients with mismatch repair gene defect was higher than those without gene defect. The differences were statistically significant for only progression-free survival and endometrial cancer-specific survival: 87.7% (95% confidence interval = 83.0%-92.4%) vs 81.5% (95% confidence interval = 75.4%-87.6%) (p = 0.049) for progression-free survival and 91.0% (95% confidence interval = 86.9%-95.1%) vs 85.5% (95% confidence interval = 80.0%-91.0%) (p = 0.044) for endometrial cancer-specific survival, respectively. In conclusion, more than half of Thai endometrial cancer patients had mismatch repair gene defect. The patients with mismatch repair gene defect had significantly younger age (⩽ 60 years) and better prognosis in terms of early stage, negative nodal status, and longer survivals.
本研究旨在评估泰国子宫内膜癌患者中错配修复基因缺陷的患病率及其与临床病理特征和生存率的关联。对1995年1月1日至2016年12月31日在我院接受手术的患者子宫切除标本中的子宫内膜癌（EMC）组织的福尔马林固定石蜡包埋块进行评估，检测4种错配修复蛋白（MLH1、PMS、MSH2、MSH6）的免疫组化表达。错配修复基因缺陷通过至少1种蛋白的阴性表达来确定。在纳入研究的385例EMC患者中，平均年龄为57.3±10.8岁，62.3%的患者年龄≤60岁。最常见的错配修复基因缺陷是MSH6（38.7%），其次是PMS2（34.3%）、MLH1（33.2%）和MSH2（16.4%）。总体而言，55.1%的患者至少有一种蛋白呈阴性表达。我们发现，年龄≤60岁、疾病处于早期且淋巴结状态为阴性的患者错配修复基因缺陷显著高于其他对照组：年龄方面为59.2% vs 48.3%（p = 0.037），分期方面为58.2% vs 45.2%（p = 0.027），淋巴结状态方面为58.1% vs 44.6%（p = 0.048）。错配修复基因缺陷患者的5年无进展生存率、总生存率和子宫内膜癌特异性生存率高于无基因缺陷的患者。仅无进展生存率和子宫内膜癌特异性生存率的差异具有统计学意义：无进展生存率为87.7%（95%置信区间 = 83.0% - 92.4%） vs 81.5%（95%置信区间 = 75.4% - 87.6%）（p = 0.049），子宫内膜癌特异性生存率为91.0%（95%置信区间 = 86.9% - 95.1%） vs 85.5%（95%置信区间 = 80.0% - 91.0%）（p = 0.044）。总之，超过一半的泰国子宫内膜癌患者有错配修复基因缺陷。错配修复基因缺陷的患者年龄显著更小（≤60岁），在疾病早期、淋巴结状态为阴性及生存率较长方面预后更好。
