湖南地区结直肠癌中错配修复蛋白MSH2、MSH6、MLH1及PMS2的表达与临床病理特征的关系(1)
【摘要】 目的：探讨错配修复蛋白MSH2、MSH6、MLH1及PMS2在结直肠癌(Colorectal cancer，CRC)组织中的表达及其临床病理意义。方法：应用免疫组化PV法检测结直肠癌组织(191例)中MSH2、MSH6、MLH1及PMS2的表达情况，将4种MMR蛋白中的1种及以上表达缺失判定为错配修复基因缺陷(dMMR)，全部阳性判定为错配修复基因完整(pMMR)，并分析其与临床病理特征的关系。结果：(1)191例中pMMR组159例，MMR蛋白表达率83.2%，dMMR组32例，MMR蛋白缺失率为16.8%。MSH2、MSH6、MLH1及PMS2的表达缺失率分别为2.6%、2.6%、8.9%及14.7%;其中共同缺失表达类型为MSH2-MSH6、MLH1-PMS2及4种共同缺失者分别为4例(2.1%)、14例(7.3%)、2例(1.0%)。(2)CRC癌患者dMMR与pMMR在肿瘤部位、肿瘤直径、分化程度等临床病理特征方面比较，差异均有统计学意义(P<0.05)，而在性别、年龄、浸润深度、淋巴结转移、脉管侵犯和神经侵犯等方面比较，差异均无统计学意义(P>0.05)。结论：MMR蛋白与CRC临床病理特征关系密切。MMR蛋白对预测CRC的恶性程度、临床预后及发病机制方面可能有指导意义。
【关键词】 结直肠癌; MSH2; MSH6; MLH1; PMS2; 免疫组织化学
【Abstract】 Objective：To investigate the expression of mismatch repair protein( MLH1，MSH2，MSH6 and PMS2)with clinicopathological features in colorectal cancer.Method：The expression of mismatch repair protein MLH1，MSH2，MSH6 and PMS2 were determined by immumohistochemistry in 191 cases of CRC.Deletion of one or more of the four MMR proteins were identified as mismatch repair gene defects(dMMR)，and all positives were mismatch repair gene integrity(pMMR)，their relationship with clinicopathological features was analyzed.Result：Negative staining of MMR proteins was found in 32 cases analyzed.The frequency of loss expression in MSH2，MSH6，MLH1and PMS2 was 2.6%，2.6%，8.9% and 14.7% respectively.Among them，double proteins absence were found in MSH2/MSH6 in 4 cases(2.1%)and MLH1/PMS2 in 14 cases(7.3%).There 2 cases(1.0%)with 4 protein deletion.Patients with dMMR and pMMR in CRC had difference in tumor location，tumor diameter and degree of differentiation(P<0.05)，but had no obvious difference in gender，age，invasion depth，lymph node metastasis，vascular invasion and neurological invasion(P>0.05).Conclusion：There is a close relationship between MMR proteins and the clinicopathological characteristics of colorectal cancer.MMR proteins may be biological indicators for estimating malignant degree，clinical prognosis and pathogenesis mechanism of CRC.
【Key words】 Colorectal cancer; MSH2; MSH6; MLH1; PMS2; Immunohistochemistry
First-author’s address：Shenzhen Sixth People’s Hospital，Shenzhen 518052，China
doi：10.3969/j.issn.1674-4985.2019.13.028
結直肠癌(Colorectal cancer，CRC)是世界范围内常见的恶性肿瘤，因其在癌症进展后预后不良导致的高死亡率，使其成为癌症相关死亡的第二大原因[1-3]。全世界每年新发病例估计有140万例，死亡病例为693 900例。在中国，CRC死亡率在恶性肿瘤死亡率中排名第五，严重危害人类健康[4]。据报道，多种危险因素导致结直肠癌的发生，如不健康的饮食，肥胖和吸烟。尽管早期CRC患者的5年生存率约为90%，但只有39%的病例在早期被诊断出来。当其扩散到远处器官时，5年生存率下降到12.5%[5]。临床的挑战是能够在早期识别CRC患者，从而选择更为合适的治疗方案。因此深入了解参与CRC侵袭和转移的相关分子机制十分必要，具有重要的临床意义。结直肠癌是一个复杂的，多步骤的过程，由多因素、多信号通路和多种基因突变导致。约15%的结肠癌是由DNA错配修复(mismatch repair，MMR)基因缺陷所致。DNA错配修复系统的主要功能在于修复那些在DNA复制过程中逃脱DNA聚合酶即时校读的错配碱基，以维持基因组的稳定性和避免细胞突变，从而间接抑制肿瘤的发生[6]。越来越多的研究表明人体不同部位的多种不同类型的肿瘤都可能与MMR的表达缺失密切相关。本研究采用免疫组化PV法检测结直肠癌中MSH2、MSH6、MLH1及PMS2的表达情况，探讨其与结直肠癌临床病理特征的关系，为结直肠癌侵袭转移及预后判断提供客观指标，现报道如下。, 百拇医药(吴畅 张继君 赵夫娟 王俊普 文继舫)
【关键词】 结直肠癌; MSH2; MSH6; MLH1; PMS2; 免疫组织化学
【Abstract】 Objective：To investigate the expression of mismatch repair protein( MLH1，MSH2，MSH6 and PMS2)with clinicopathological features in colorectal cancer.Method：The expression of mismatch repair protein MLH1，MSH2，MSH6 and PMS2 were determined by immumohistochemistry in 191 cases of CRC.Deletion of one or more of the four MMR proteins were identified as mismatch repair gene defects(dMMR)，and all positives were mismatch repair gene integrity(pMMR)，their relationship with clinicopathological features was analyzed.Result：Negative staining of MMR proteins was found in 32 cases analyzed.The frequency of loss expression in MSH2，MSH6，MLH1and PMS2 was 2.6%，2.6%，8.9% and 14.7% respectively.Among them，double proteins absence were found in MSH2/MSH6 in 4 cases(2.1%)and MLH1/PMS2 in 14 cases(7.3%).There 2 cases(1.0%)with 4 protein deletion.Patients with dMMR and pMMR in CRC had difference in tumor location，tumor diameter and degree of differentiation(P<0.05)，but had no obvious difference in gender，age，invasion depth，lymph node metastasis，vascular invasion and neurological invasion(P>0.05).Conclusion：There is a close relationship between MMR proteins and the clinicopathological characteristics of colorectal cancer.MMR proteins may be biological indicators for estimating malignant degree，clinical prognosis and pathogenesis mechanism of CRC.
【Key words】 Colorectal cancer; MSH2; MSH6; MLH1; PMS2; Immunohistochemistry
First-author’s address：Shenzhen Sixth People’s Hospital，Shenzhen 518052，China
doi：10.3969/j.issn.1674-4985.2019.13.028
結直肠癌(Colorectal cancer，CRC)是世界范围内常见的恶性肿瘤，因其在癌症进展后预后不良导致的高死亡率，使其成为癌症相关死亡的第二大原因[1-3]。全世界每年新发病例估计有140万例，死亡病例为693 900例。在中国，CRC死亡率在恶性肿瘤死亡率中排名第五，严重危害人类健康[4]。据报道，多种危险因素导致结直肠癌的发生，如不健康的饮食，肥胖和吸烟。尽管早期CRC患者的5年生存率约为90%，但只有39%的病例在早期被诊断出来。当其扩散到远处器官时，5年生存率下降到12.5%[5]。临床的挑战是能够在早期识别CRC患者，从而选择更为合适的治疗方案。因此深入了解参与CRC侵袭和转移的相关分子机制十分必要，具有重要的临床意义。结直肠癌是一个复杂的，多步骤的过程，由多因素、多信号通路和多种基因突变导致。约15%的结肠癌是由DNA错配修复(mismatch repair，MMR)基因缺陷所致。DNA错配修复系统的主要功能在于修复那些在DNA复制过程中逃脱DNA聚合酶即时校读的错配碱基，以维持基因组的稳定性和避免细胞突变，从而间接抑制肿瘤的发生[6]。越来越多的研究表明人体不同部位的多种不同类型的肿瘤都可能与MMR的表达缺失密切相关。本研究采用免疫组化PV法检测结直肠癌中MSH2、MSH6、MLH1及PMS2的表达情况，探讨其与结直肠癌临床病理特征的关系，为结直肠癌侵袭转移及预后判断提供客观指标，现报道如下。, 百拇医药(吴畅 张继君 赵夫娟 王俊普 文继舫)