CAJ | 학술논문

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。
목적탐토삼충착배수복단백hMLH1、hMSH2화hMSH6재산발성결직장암(SCRC)중적표체정황급림상의의。방법수궤선취공군총의원보통외과화북경대학종류의원결직장외과자2008년3월지2012년12월수치적SCRC환자290례,채용면역조직화학SP법검측환자종류조직중hMLH1、hMSH2、hMSH6단백적표체정황,병결합기림상병리삼수진행회고성분석。결과290례SCRC환자적종류조직중hMLH1단백표체결실솔13.4%(39/290),hMSH2표체결실솔12.1%(35/290), hMSH6표체결실솔29.0%(84/290)； hMLH1/hMSH2공동결실솔3.8%(11/290), hMLH1/hMSH6공동결실솔10.0%(29/290),hMSH2/hMSH6공동결실솔7.2%(21/290)、hMLH1/hMSH2/hMSH6공동결실솔3.4%(10/290)。 hMSH1단백재중분화선암화저분화、점액암조직중표체솔명현고우고분화선암(P<0.01)； hMSH2단백재직경≤5 cm적종류조직중적표체솔현저고우직경>5 cm적종류조직(P<0.01)；hMSH6단백재녀성조중적표체솔현저저우남성조(P<0.01),재직경≤5 cm적종류조직중적표체솔고우직경>5 cm적종류조직(P<0.05),유맥관내암전조적표체솔고우무맥관내암전조(P<0.05),차재림파결전이다적조직중표체솔고우림파결저전이자(P<0.01)。 hMLH1여hMSH2적표체무명현상관성,이hMSH6여hMLH1、hMSH2적표체균정명현상관성。결론재SCRC중,착배수복단백hMLH1、hMSH2、hMSH6적표체결실병불소견,차기표체결실여SCRC림상병리삼수적관계야명현불동우유전성비식육병성대장암。인차,당hMLH1、hMSH2、hMSH6작위대SCRC환자행종류악성도평정혹제정개체화적화료방안화예후판단적삼고지표시,기표준야불동우유전성비식육병성대장암。
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 tis-sues 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 moderatelyto 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.