西藏地区手术切除结直肠癌病理类型及错配修复蛋白、人表皮生长因子受体2、Pan-TRK表达和Eostein-Barr病毒感染情况分析

Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet

目的 分析西藏地区手术切除结直肠癌的病理类型及错配修复蛋白、人表皮生长因子受体2(HER2)、Pan-TRK表达和Epstein-Barr病毒(EBV)感染情况,为西藏地区结直肠癌患者精准诊疗提供依据。方法 选取2013年12月至2021年7月西藏自治区人民医院病理科存档的经手术切除确诊的结直肠癌病例79例,收集患者临床和病理资料,采用免疫组织化学染色检测错配修复蛋白、HER2、Pan-TRK的表达,并对HER2表达在2+及以上病例进行HER2基因荧光原位杂交检测,采用EBV编码小RNA原位杂交检测EBV感染情况。结果 79例手术切除结直肠癌病例,男女比例1.26∶1,平均年龄(57.06±12.74)岁(24~83岁),其中4例接受术前新辅助化疗。57例(57/79,72.15%)为结肠占位(31例为右半结肠,26例为左半结肠),22例(22/79,27.85%)为直肠占位;肿瘤最大径1~20 cm,平均(6.61±3.33)cm。75例(75/79,94.94%)为腺癌。21例高度肿瘤出芽的病例中12例(12/21,57.14%)出现淋巴结转移,23例中度肿瘤出芽的病例中13例(13/23,56.52%)出现淋巴结转移,31例低度肿瘤出芽的病例中2例(2/31,6.45%)出现淋巴结转移,中、高度与低度肿瘤出芽之间的淋巴结转移率差异均有统计学意义(P均<0.001)。10例(10/65,15.38%)错配修复蛋白表达缺失,其中5例MSH2和MSH6同时表达缺失,4例MLH1和PMS2同时表达缺失,1例MSH6表达缺失;65例Pan-TRK表达均为阴性;60例HER2表达结果为0或1+,5例为2+,HER2基因荧光原位杂交检测均未见阳性信号,EBV编码小RNA原位杂交检测1例(1/65,1.54%)阳性。结论 西藏地区手术切除结直肠癌病例以右半结肠非特殊型腺癌最多见,15%的病例存在错配修复蛋白缺陷,EBV相关性结直肠癌少见,罕见Pan-TRK表达及HER2基因扩增,中、高度肿瘤出芽的结直肠癌病例更容易发生淋巴结转移。

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet.Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People’s Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+or above.EBV was detected by in situ hybridization with EBV-encoded small RNA.Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26∶1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+in 60 patients and 2+in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient.Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15%of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.