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中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2015, Vol. 09 ›› Issue (03) : 193 -197. doi: 10.3877/cma.j.issn.1674-0793.2015.03.005

所属专题： 文献；

论著

错配修复蛋白hMLH1、hMSH2和hMSH6在散发性结直肠癌中的表达及意义
于鹏飞1, 费翔1, 魏学明1, 李明2, 顾晋2, 顾国利1,†()   
  1. 1. 100142　北京，安徽医科大学空军临床医院　空军总医院普通外科
    2. 100142　北京，北京大学肿瘤医院结直肠外科
  • 收稿日期:2015-03-06 出版日期:2015-06-01
  • 通信作者: 顾国利
  • 基金资助:
    首都市民健康项目培育课题(Z131100004013021)

Expression of mismatch repair proteins hMLH1, hMSH2 and hMSH6 in sporadic colorectal cancer

Pengfei Yu1, Xiang Fei1, Xueming Wei1, Ming Li2, Jin Gu2, Guoli Gu1,†()   

  1. 1. The Air Force Clinical College of Anhui Medical University, Department of General Surgery, the Air Force General Hospital, Beijing 100142, China
    2. Department of Colorectal Surgery, Beijing Cancer Hospital, Beijing 100142, China
  • Received:2015-03-06 Published:2015-06-01
  • Corresponding author: Guoli Gu
  • About author:
    Corresponding author: Gu Guoli, Email:
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于鹏飞, 费翔, 魏学明, 李明, 顾晋, 顾国利. 错配修复蛋白hMLH1、hMSH2和hMSH6在散发性结直肠癌中的表达及意义[J]. 中华普通外科学文献(电子版), 2015, 09(03): 193-197.

Pengfei Yu, Xiang Fei, Xueming Wei, Ming Li, Jin Gu, Guoli Gu. Expression of mismatch repair proteins hMLH1, hMSH2 and hMSH6 in sporadic colorectal cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2015, 09(03): 193-197.

目的

探讨三种错配修复蛋白hMLH1、hMSH2和hMSH6在散发性结直肠癌(SCRC)中的表达情况及临床意义。

方法

随机选取空军总医院普通外科和北京大学肿瘤医院结直肠外科自2008年3月至2012年12月收治的SCRC患者290例,采用免疫组织化学SP法检测患者肿瘤组织中hMLH1、hMSH2、hMSH6蛋白的表达情况,并结合其临床病理参数进行回顾性分析。

结果

290例SCRC患者的肿瘤组织中hMLH1蛋白表达缺失率13.4%(39/290),hMSH2表达缺失率12.1%(35/290), hMSH6表达缺失率29.0%(84/290); hMLH1/hMSH2共同缺失率3.8%(11/290), hMLH1/hMSH6共同缺失率10.0%(29/290),hMSH2/hMSH6共同缺失率7.2%(21/290)、hMLH1/hMSH2/hMSH6共同缺失率3.4%(10/290)。hMSH1蛋白在中分化腺癌和低分化、黏液癌组织中表达率明显高于高分化腺癌(P<0.01); hMSH2蛋白在直径≤5 cm的肿瘤组织中的表达率显著高于直径>5 cm的肿瘤组织(P<0.01);hMSH6蛋白在女性组中的表达率显著低于男性组(P<0.01),在直径≤5 cm的肿瘤组织中的表达率高于直径>5 cm的肿瘤组织(P<0.05),有脉管内癌栓组的表达率高于无脉管内癌栓组(P<0.05),且在淋巴结转移多的组织中表达率高于淋巴结低转移者(P<0.01)。hMLH1与hMSH2的表达无明显相关性,而hMSH6与hMLH1、hMSH2的表达均呈明显相关性。

结论

在SCRC中,错配修复蛋白hMLH1、hMSH2、hMSH6的表达缺失并不少见,且其表达缺失与SCRC临床病理参数的关系也明显不同于遗传性非息肉病性大肠癌。因此,当hMLH1、hMSH2、hMSH6作为对SCRC患者行肿瘤恶性度评定或制定个体化的化疗方案和预后判断的参考指标时,其标准也不同于遗传性非息肉病性大肠癌。

关键词: 错配修复蛋白, 散发性结直肠癌, 遗传性非息肉病性大肠癌
Objective

To investigate the expression and clinical significance of mismatch repair proteins hMLH1, hMSH2 and hMSH6 in sporadic colorectal carcinoma (SCRC).

Methods

Two hundred and ninety patients with SCRC were studied, who underwent surgery in the Department of General Surgery, the Air Force General Hospital and the Department of Colorectal Surgery, Beijing Cancer Hospital from March 2008 to December 2012. Immunohistochemistry was used to detect hMLH1, hMSH2 and hMSH6 expression in tumor tissues. The relationship between expression and clinicopathological data was analyzed retrospectively.

Results

The absent expression rates of hMLH1, hMSH2 and hMSH6 only in tumor tissues were 13.4% (39/290), 12.1% (35/290) and 29.0% (84/290), respectively. The absent expression rates of hMLH1 and hMSH2, hMLH1 and hMSH6, hMSH2 and hMSH6, and hMLH1, hMSH2 and hMSH6 were 3.8% (11/290), 10.0% (29/290), 7.2% (21/290) and 3.4% (10/290), respectively. The absent expression rate of hMLH1 in highly differentiated adenocarcinoma tissues was obviously higher than that of moderately to poorly differentiated adenocarcinoma and mucous carcinomas tissues (P<0.01). In the tumor tissues less than 5 cm, the expression level of hMSH2 was obviously higher than that of more than 5 cm, so as hMSH6 (P<0.05). The expression rate of hMSH6 in female group was clearly higher than that of male group (P<0.01), and the expression rate of hMSH6 in high lymph node metastasis of tumor tissues was higher than that of low lymph node metastasis.

Conclusions

The absent expressions of hMLH1, hMSH2 and hMSH6 are common in SCRC, and the clinicopathological parameters of SCRC is obviously different from hereditary nonpolyposis colorectal cancer (HNPCC). Therefore, the biological effects, indicators for evaluation of degree of malignancy, individualized chemotherapy regimens and prognostic indicators may be different from those in HNPCC.

Key words: Mismatch repair protein, Sporadic colorectal cancer, Hereditary nonpolyposis colorectal cancer
表1 hMLH1、hMSH2、hMSH6表达缺失与SCRC临床病理参数间的关系(例,χ2检验)
项目 例数 hMLH1 hMSH2 hMSH6
- + χ2值 P值 - + χ2值 P值 - + χ2值 P值
性别 ? ? ? 0.07 0.795 ? ? 1.12 0.289 ? ? 20.07 <0.01
? 男 158 22 136 ? ? 22 136 ? ? 63 95 ? ?
? 女 132 17 115 ? ? 13 119 ? ? 21 111 ? ?
年龄(岁) ? ? ? 0.49 0.483 ? ? 2.89 0.058 ? ? 1.42 0.233
? <60 119 14 105 ? ? 19 100 ? ? 39 80 ? ?
? ≥60 171 25 146 ? ? 16 155 ? ? 45 126 ? ?
肿瘤最大径(cm) ? ? ? 0.66 0.415 ? ? 10.74 0.020 ? ? 4.26 0.024
? >5 95 15 80 ? ? 20 75 ? ? 35 60 ? ?
? ≤5 195 24 171 ? ? 15 180 ? ? 49 146 ? ?
部位 ? ? ? 2.49 0.646 ? ? 3.12 0.514 ? ? 1.56 0.816
? 右半结肠 82 12 70 ? ? 14 68 ? ? 28 54 ? ?
? 左半结肠 21 5 16 ? ? 3 18 ? ? 6 15 ? ?
? 乙状结肠 77 9 68 ? ? 7 70 ? ? 20 57 ? ?
? 直肠 110 13 97 ? ? 11 99 ? ? 30 80 ? ?
形态 ? ? ? 1.81 0.173 ? ? 3.23 0.139 ? ? 1.41 0.472
? 溃疡型 225 27 198 ? ? 23 202 ? ? 69 156 ? ?
? 隆起型 65 12 53 ? ? 12 53 ? ? 15 50 ? ?
浸润深度 ? ? ? 0.10 0.953 ? ? 5.08 0.227 ? ? 2.46 0.367
? 肌层内 54 7 47 ? ? 9 45 ? ? 17 37 ? ?
? 浆膜 203 27 176 ? ? 19 184 ? ? 54 149 ? ?
? 浆膜外 33 5 28 ? ? 7 26 ? ? 13 20 ? ?
分化程度 ? ? ? 18.39 <0.01 ? ? 2.72 0.322 ? ? 0.89 0.570
? 高分化 20 9 11 ? ? 4 16 ? ? 4 16 ? ?
? 中分化 183 20 163 ? ? 18 165 ? ? 55 128 ? ?
? 低分化、黏液腺瘤 87 10 77 ? ? 13 74 ? ? 25 62 ? ?
脉管内癌栓 ? ? ? 0.13 0.654 ? ? 0.71 0.398 ? ? 4.83 0.028
? 有 66 8 58 ? ? 6 60 ? ? 12 54 ? ?
? 无 224 31 193 ? ? 29 195 ? ? 72 152 ? ?
淋巴结转移 ? ? ? 1.61 0.389 ? ? 2.46 0.615 ? ? 16.70 0.003
? 0 124 20 104 ? ? 11 113 ? ? 44 80 ? ?
? 1~3 95 12 83 ? ? 15 80 ? ? 33 62 ? ?
? ≥4 71 7 64 ? ? 9 62 ? ? 7 64 ? ?
表2 hMLH1、hMSH2、hMSH6蛋白在SCRC中表达的相关性
项目 hMLH1 hMSH2
(+~++) (-) χ2值 P值 (+~++) (-) χ2值 P值
hMSH2 ? ? 0.31 >0.05 ? ? ? ?
? (+~++) 227 28 ? ? - - - -
? (-) 24 11 ? ? - - ? ?
hMSH6 ? ? 31.15 <0.01 ? ? ? ?
? (+~++) 196 10 ? ? 192 14 ? ?
? (-) 55 29 ? ? 63 21 25.00 <0.01
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