肺胃型黏液腺癌具有独特的临床病理特征

doi:10.6040/j.issn.1671-7554.0.2024.0576

摘要/Abstract

摘要： 目的探讨肺胃型黏液腺癌(gastric mucinous adenocarcinoma, GMA)的形态特征、临床病理特点、基因改变及临床预后,为肺黏液腺癌的个体化治疗提供帮助。方法回顾性分析肺浸润性非黏液腺癌(invasive non-mucinous lung adenocarcinoma, INMA)48例、浸润性黏液腺癌(invasive mucinous adenocarcinoma, IMA)40例的资料,其中IMA包括单纯性黏液腺癌(simple invasive mucinous adenocarcinoma, SIMA)30例及黏液-非黏液混合型腺癌(mucinous and non-mucinous mixed adenocarcinoma, MNMA)10例,SIMA根据形态进一步分为GMA、柱状细胞型黏液腺癌(colunmar cell mucinous adenocarcinoma, CMA)及混合型单纯性黏液腺癌(mixed simple invasive mucinous adenocarcinoma, MSIMA)。收集患者的临床病理资料。对所有石蜡样本行免疫组织化学(immunohistochemistry, IHC)检测人黏蛋白5ac(mucin 5ac, MUC5ac)、人黏蛋白6(mucin 6, MUC6)、甲状腺转录因子-1(thyroid transcription factor-1, TTF-1)、细胞角蛋白7(cytokeratin 7, CK7)、细胞角蛋白5/6(cytokeratin 5/6, CK5/6)等指标,并对所有样本行聚合酶链式反应(polymerase chain reaction, PCR)或二代测序(next-generation sequencing, NGS)检测肺癌相关驱动基因。结果 GMA的肿瘤平均直径显著小于CMA、MSIMA、MNMA及INMA中的肿瘤平均直径,发病年龄略高于其他类型腺癌,且好发于肺下叶。MUC6在GMA中的阳性率为92.93%,显著高于在CMA(8.33%)、MNMA(20.00%)及INMA(0%)中的阳性率,差异有统计学意义(P<0.001);而TTF-1和CK7在GMA中的表达率显著低于在MNMA及INMA中的表达率(P均<0.001)。14例GMA中,10例伴有KRAS基因点突变,比例显著高于CMA、MNMA及INMA。且MUC6的表达与KRAS基因突变呈显著正相关(Pearson 相关系数=0.590)。结论 GMA直径较小,好发于肺下叶,高表达 MUC6,且KRAS基因突变率高,具有独特的病理、临床及分子特点,应作为独立类型。

关键词: 肺, 浸润性黏液腺癌, 人黏蛋白6, 甲状腺转录因子-1, KRAS基因

Abstract: Objective To investigate the morphological characteristics, clinicopathological features, genetic alterations, and clinical outcomes of gastric mucinous adenocarcinoma(GMA), so as to supply personalized treatment for lung mucinous adenocarcinoma. Methods A total of 48 cases of invasive non-mucinous lung adenocarcinoma(INMA)and 40 cases of invasive mucinous adenocarcinoma(IMA)were retrospectively analyzed. The IMA cases included 30 cases of simple invasive mucinous adenocarcinoma(SIMA)and 10 cases of mucinous and non-mucinous mixed adenocarcinoma(MNMA). SIMA was further categorized into GMA, columnar cell mucinous adenocarcinoma(CMA), and mixed simple invasive mucinous adenocarcinoma(MSIMA). The clinicopathological data from the patients were collected. Immunohistochemical analysis was performed on all paraffin-embedded samples to detect the expressions of mucin 5ac(MUC5ac), mucin 6(MUC6), thyroid transcription factor-1(TTF-1), cytokeratin 7(CK7), and cytokeratin 5/6(CK5/6). Additionally, polymerase chain reaction(PCR)or next-generation sequencing(NGS)was conducted to detect lung cancer-related genes. Results Compared with CMA,MSIMA,MNMA and INMA, the mean diameter of GMA was significantly smaller and the age of onset was slightly higher. Most of GMA occured in the lower lobes of the lungs. The positive rate of MUC6 in GMA was 92.93%, which was significantly higher than those in CMA(8.33%), MNMA(20.00%), and INMA(0%), with a statistically significant difference(P<0.001). The expression rates of TTF-1 and CK7 in GMA were significantly lower than those in MNMA and INMA(P<0.001). KRAS gene mutation rate in GMA was higher than that in CMA, MNMA, and INMA. Additionally, MUC6 expression was positively correlated with KRAS gene mutations(Pearson correlation coefficient= 0.590). Conclusion GMA is characterized by small tumor size, high occurrence rate in the lower lobe of the lung, high MUC6 expression, and high KRAS gene mutation rate. These unique pathological, clinical, and molecular features suggest that GMA should be considered a distinct subtype.

Key words: Lung, Invasive mucinous adenocarcinoma, Human mucin 6, Thyroid transcription factor-1, KRAS gene

中图分类号:

R365

郝晓梦,于泽源,张晓芳. 肺胃型黏液腺癌具有独特的临床病理特征[J]. 山东大学学报 (医学版), 2024, 62(8): 107-116.

HAO Xiaomeng, YU Zeyuan, ZHANG Xiaofang. Gastric mucinous adenocarcinoma of lung has unique clinical and pathological characteristics[J]. Journal of Shandong University (Health Sciences), 2024, 62(8): 107-116.

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