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肺肠型腺癌的临床病理学及分子学特征分析

Clinicopathological and molecular features of pulmonary enteric adenocarcinoma

摘要:

目的:探讨肺肠型腺癌(pulmonary enteric adenocarcinoma,PEAC)的临床病理学及分子学特征。方法:收集2015至2019年郑州大学附属肿瘤医院确诊的PEAC19例,复查相关临床及病理资料,同时采用免疫组织化学(IHC)法检测相关免疫表型,扩增阻滞突变系统(ARMS)法和荧光原位杂交(FISH)法检测表皮生长因子受体(EGFR)、KRAS、间变性淋巴瘤激酶(ALK)基因的表达情况,随访患者,复习相关文献并总结分析。结果:19例患者中男性10例,女性9例,平均年龄58岁(33~71岁)。镜下见肿瘤组织呈中到高分化的腺样和/或乳头样生长方式,肿瘤细胞呈高柱状,有时假复层排列。部分腺腔内可见炎性坏死和散在的碎裂核。IHC显示该组病例不同程度表达细胞角蛋白(CK)7(19/19)、甲状腺转录因子1(TTF1,8/19)、Napsin A(6/19)、Villin(17/19)、CK20(16/19)和CDX2(10/19)。基因检测发现9例(9/19)KRAS基因突变,1例(1/19)EGFR基因突变,1例(1/19)ALK基因断裂信号阳性。检索国内外有关PEAC的文献报道并总结发现KRAS在PEAC中的突变率远远高于EGFR及ALK的突变率。19例病例均行手术切除,11例术后行化疗或放化疗。结论:PEAC是肺腺癌的一种少见变异类型,与结直肠腺癌有相似的组织细胞学形态。但是详细病史、组织学异质性、CK7 +/Villin +的免疫组合以及KRAS基因突变率高是诊断的要点。预后有待于长期随访及大数据统计。

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Objective:To investigate the clinicopathological and molecular characteristics of pulmonary enteric adenocarcinoma (PEAC).Methods:The clinical and pathological data of 19 cases of PEAC in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively collected from 2015 to 2019. Immunohistochemistry (IHC) was used to detect the relevant immunophenotypes, amplification refractory mutation system (ARMS) and fluorescence in situ hybridization (FISH) were used to detect the expression of EGFR, KRAS and ALK genes. The patients were followed up, and the relevant literature was reviewed and analyzed.Results:There were 19 cases, including 10 males and 9 females, with a mean age of 58 years (range 33-71 years). Microscopically, the tumors showed moderately to highly differentiated adenoid and/or papillary growth patterns. The tumor cells were highly columnar and sometimes showed pseudostratification. Inflammatory necrosis and scattered nuclear fragmentation were seen in some glandular lumens. IHC showed variable expression of CK7 (19/19), TTF1 (8/19), Napsin A (6/19), villin (17/19), CK20 (16/19) and CDX2 (10/19). Molecular testing showed KRAS mutation in nine cases (9/19), EGFR mutation in one case (1/19), and positive ALK split signal in one case (1/19). In the literature, the reported mutation rate of KRAS in PEAC was much higher than that of EGFR and ALK. All 19 cases underwent surgical resection and 11 cases were subjected to chemotherapy or radiotherapy.Conclusions:PEAC is a rare variant of invasive pulmonary adenocarcinoma, and has similar histological and cytological features to that of colorectal adenocarcinoma. However, detailed medical history, histologic heterogeneity, an IHC combination of CK7 +/villin + and high KRAS mutation rate are the key points of diagnosis. The prognosis needs long-term follow-up and big data statistics.

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