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  • Title: [Combined application of immunohistochemical markers to identify pathologic subtypes of ampullary carcinoma and its clinical significance].
    Author: Liu FF, Shen DH, Wang HL, Ma YT, Yuan F, Liu J, Chen L, Song QJ, Zhang YY.
    Journal: Zhonghua Bing Li Xue Za Zhi; 2019 Feb 08; 48(2):92-97. PubMed ID: 30695858.
    Abstract:
    Objective: To investigate the expression of immunomarkers CK7, CK20, CK17, CDX2, MUC1 and MUC2 in primary adenocarcinoma of the ampulla of Vater, to explore the role of these markers in the histopathologic subclassification of ampullary carcinoma; and to provide biologic basis for precision treatment of patients with different types of ampullary carcinoma. Methods: Forty-two cases of primary ampullary carcinoma were collected at Peking University People's Hospital, from 2012 to 2018 year. There were 22 males and 20 females. Aged range 42 to 88 years old, with mean aged (62±11) years. Among the patients, 6 was high differentiation, 19 median differentiation, and 17 low differentiation. Immunohistochemical studies on the expression of CK7, CK20, CK17, CDX2, MUC1 and MUC2 were performed in 42 cases of primary ampullary carcinoma. The relationship between different ampullary carcinoma subtypes and clinicopathologic survival data was analyzed using SPSS 16.0 statistical software. Results: Three histopathologic subtypes were observed. Among 42 cases, 8(19.0%)were classified as intestinal subtype, which showed a positive expression rate of 8/8 for both CK20 and CDX2, and 5/8 for MUC2. Both CK7 and CK17 were weakly expressed in one case (1/8). No expression was observed for MUC1 in this subtype. Twenty-two (52.4%,22/42) cases were classified as pancreaticobiliary subtype, which showed a positive expression rate of 100.0%(22/22) for both CK7 and MUC1, and 90.9% (20/22) for CK17. No expression was observed for CK20, CDX2 and MUC2.The remaining 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns. The expression frequencies of these 6 immunomarkers in different subtypes of ampullary carcinoma did not correlate with various clinicopathologic factors such as patient gender and age, tumor size, histologic differentiation, pancreatic and bile duct invasion, or the depth of duodenal invasion. However, stage Ⅲ+Ⅳ diseases were more commonly seen in pancreaticobiliary type (63.6%,14/22) than intestinal type (2/8) and mixed type (3/9; χ(2)=6.508, P=0.039). Follow-up data showed a trend of better survival rate for patients with intestinal subtype than those with mixed and pancreaticobiliary subtypes. Conclusions: Ampullary carcinoma can be subclassified into three different subtypes using a panel of six immunomarkers, especially for the identification of subtypes of poorly differentiated carcinoma. CK7, CK17 and MUC1 are major markers of pancreaticobiliary subtype, whereas CK20, CDX2 and MUC2 are useful markers for intestinal subtype. The mixed subtype variably expresses these markers. The prognosis of patients with intestinal subtype appears better than that of pancreaticobiliary and mixed subtypes. Accurate subtyping of ampullary carcinoma is clinically important to patient management and prognosis assessment. 目的： 探讨蛋白标志物细胞角蛋白（CK）7、CK20、CK17、CDX2、MUC1、MUC2在原发壶腹癌中的表达，分析它们在壶腹癌病理亚型分型中的作用，为临床精准治疗提供依据。 方法： 收集北京大学人民医院2012至2018年原发壶腹癌手术切除标本42例。其中男性22例，女性20例；高分化腺癌6例，中分化腺癌19例，低分化腺癌17例。患者年龄42~88岁，平均年龄（62±11）岁。利用免疫组织化学方法研究CK7、CK20、CK17、CDX2、MUC1、MUC2在42例壶腹癌中的表达，并进行病理亚型分型，同时分析不同壶腹癌亚型与患者临床病理因素之间的关系。统计学方法采用SPSS 16.0分析软件进行χ(2)检验分析和Kaplan-Meier生存分析。 结果： 42例壶腹癌中有3种病理亚型，19.0%（8/42）为肠型壶腹癌，CK20和CDX2的阳性表达比例均为8/8，MUC2为5/8，CK7和CK17均为1/8弱阳性表达，MUC1无阳性表达（0/8）。胰胆管型壶腹癌占52.4%（22/42），CK7和MUC1的阳性表达率均为100.0%（22/22），CK17为90.9%（20/22），CK20、CDX2和MUC2均无阳性表达（0/22）。28.6%（12/42）为混合型壶腹癌，可见几种蛋白不同程度的共表达。6种蛋白在壶腹癌3种病理亚型中的表达与患者的性别、年龄、肿瘤大小、组织学分化、胰腺和胆管侵犯、十二指肠侵犯深度、生存等临床病理因素无显著性相关。42例壶腹癌中胰胆管型的Ⅲ+Ⅳ期比例（63.6%，14/22）显著多于肠型（2/8）和混合型（3/9）的Ⅲ+Ⅳ期（χ(2)=6.508，P=0.039）。随访60个月内，肠型患者的生存率有高于混合型和胰胆管型的趋势。 结论： 联合应用CK7、CK20、CK17、CDX2、MUC1和MUC2等6种标志物有助于壶腹癌病理亚型分型，特别是对于鉴定低分化癌的亚型具有重要意义。CK7、CK17和MUC1主要为胰胆管型的标志物，CK20、CDX2、MUC2为肠型标志物，6种蛋白呈现不同程度混合共表达时提示是同时存在肠型和胰胆管型的混合型壶腹癌。肠型患者预后好于混合型和胰胆管型。准确报告壶腹癌及其亚型是临床化疗方案选择和预后评估的重要依据。.
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