错配修复蛋白表达与乳腺癌新辅助化疗效果的关系

目的探究错配修复（MMR）蛋白表达与乳腺癌新辅助化疗（NACT）疗效的关系。 方法收集潍坊市人民医院2016年1月1日至2018年10月31日53例行NACT治疗的乳腺癌患者临床病理资料，采用组织芯片（TMAs）技术、免疫组织化学（IHC）方法检测NACT前乳腺癌组织4种MMR蛋白（MSH2、MSH6、PMS2、MLH1）表达水平。Miller/Payne分级G5定义为病理完全缓解（pCR），G2~4定义为部分缓解（PR），G1定义为稳定（SD）。应用SPSS 22.0软件进行数据统计分析。 结果53例乳腺癌患者NACT疗效：pCR（G5）10例（18.9％），PR（G2~4）36例（67.9％），SD（G1）7例（13.2％）。IHC结果显示：53例患者MSH2、MSH6、PMS2、MLH1蛋白均表达阳性，未发现错配修复缺陷患者。患者各临床T分期间MSH6蛋白表达强度构成比具有统计学差异（χ²=6.09，P=0.04），患者各年龄、月经状态、临床T分期、淋巴结状态、雌激素受体、孕激素受体、人表皮生长因子受体2、Ki-67指数、分子分型间MSH2、PMS2及MLH1蛋白表达强度构成比差异均无统计学意义（P＞0.05）。乳腺癌NACT疗效与MLH1（r=0.40，P=0.00）、MSH6（r=0.37，P=0.01）蛋白表达强度呈正相关关系，而与MSH2、PMS2蛋白表达强度无相关性（P＞0.05）。 结论乳腺癌活检组织MSH6、MLH1蛋白表达增强提示更好的NACT疗效，值得进一步研究。

Association between MMR protein expression and efficacy of neoadjuvant chemotherapy in breast cancer

ObjectiveTo investigate the association between the efficacy of neoadjuvant chemotherapy (NACT) and the expression of mismatch repair (MMR) proteins in breast cancer. MethodsThe clinicopathological data of 53 breast cancer patients treated with NACT from January 1, 2016 to October 31, 2018 in Weifang People's Hospital were collected, and MMR (MSH2, MSH6, PMS2, and MLH1) in pretreatment biopsies of these patients were assessed by immunohistochemistry (IHC) in tissue microarrays (TMAs). Responses to NACT were classified as pathological complete response (pCR; grade 5), partial response (PR; grades 2-4), and stable disease (SD; grade 1) according to the Miller/Payne system. The results were analyzed using SPSS 22.0 statistical software. ResultsOf the 53 breast cancer patients included, 10 (18.9%) achieved pCR (G5), 36 (67.9%) achieved PR (G2-4), and 7 (13.2%) achieved SD (G1). IHC analysis revealed that MSH2, MSH6, PMS2, and MLH1 proteins were all expressed positively in the 53 breast cancer patients and none of them were MMR-deficient. In terms of the relationship with tumor stage, the expression of MSH6 showed a statistical difference among different clinical stages (χ²=6.09, P=0.04). Age, menstrual status, clinical tumor stage, nodal status, ER, PR, HER2, Ki-67, and molecular subtypes had no significant association with the expression of MSH2, PMS2, and MLH1 (P＞0.05). The efficacy of NACT was positively associated with MLH1 (r=0.40, P=0.00) or MSH6 (r=0.37, P=0.01) expression. There was no correlation between the efficacy of NACT and MSH2 or PMS2 (P＞0.05) expression. ConclusionIncreased expression of MSH6 and MLH1 in pretreatment biopsies of breast cancer patients suggests better efficacy of NACT.