黏蛋白 5AC 增强黏液产生型肺腺癌的肿瘤异质性，并与不良预后相关。

MUC5AC enhances tumor heterogeneity in lung adenocarcinoma with mucin production and is associated with poor prognosis.

机构信息

Department of Pathology, Key Laboratory of Head and Neck Molecular Diagnosis Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China, and.

Department of Pathology, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.

出版信息

Jpn J Clin Oncol. 2020 Jun 10;50(6):701-711. doi: 10.1093/jjco/hyaa016.

DOI:10.1093/jjco/hyaa016

PMID:32083303

Abstract

OBJECTIVE

The clinicopathological significance of Mucin5AC (MUC5AC) in lung adenocarcinoma with mucin production is still unclear. This study aimed to explore MUC5AC expression in lung adenocarcinoma with mucin production and its correlation with histological subtypes, common driver mutations and its impact on prognosis.

METHODS

MUC5AC and thyroid transcription factor 1 immunohistochemistry was performed on surgical samples from 90 patients with lung adenocarcinoma with mucin production. Common driver mutations including EGFR and KRAS mutations and ALK rearrangement were detected by established methods.

RESULTS

MUC5AC was significantly associated with lymphovascular invasion (P = 0.023) and tumors with intra-cytoplasmic mucin (P < 0.001). Moreover, MUC5AC was more significant in invasive mucinous adenocarcinoma (P < 0.001), as well as in tumors with KRAS mutations (P = 0.005) and a lack of thyroid transcription factor 1 expression (P < 0.001). Conversely, MUC5AC was less significantly detected in acinar predominant adenocarcinoma (P = 0.036) and tumors with EGFR mutations (P = 0.001). Notably, MUC5AC in non-pure mucinous subtype of lung adenocarcinoma with mucin production showed more aggressive behavior, distinct expression pattern and a lack of significant correlation with thyroid transcription factor 1 (P = 0.113) when compared with pure mucinous subtype. MUC5AC-positive tumors were significantly associated with a worse prognosis compared to MUC5AC-negative tumors (P < 0.001). A multivariate survival analysis showed that MUC5AC was an independent prognosis factor for poor prognosis (P = 0.006).

CONCLUSIONS

The clinicopathological features of non-pure mucinous subtype of lung adenocarcinoma with mucin production were distinct and should be distinguished from pure mucinous subtype. MUC5AC was associated with poor prognosis and could be a potential therapeutic target for this distinct type of lung adenocarcinoma that has few effective treatments.

摘要

目的

在产生黏液的肺腺癌中，黏蛋白 5AC（MUC5AC）的临床病理意义尚不清楚。本研究旨在探讨产生黏液的肺腺癌中 MUC5AC 的表达及其与组织学亚型、常见驱动突变的相关性，以及对预后的影响。

方法

对 90 例产生黏液的肺腺癌手术标本进行 MUC5AC 和甲状腺转录因子 1 免疫组织化学染色。采用已建立的方法检测常见驱动突变，包括 EGFR 和 KRAS 突变以及 ALK 重排。

结果

MUC5AC 与血管淋巴管侵犯显著相关（P=0.023），与胞质内黏液的肿瘤显著相关（P<0.001）。此外，在浸润性黏液性腺癌（P<0.001）、KRAS 突变（P=0.005）和缺乏甲状腺转录因子 1 表达的肿瘤中，MUC5AC 更为显著（P<0.001）。相反，在腺泡为主型腺癌（P=0.036）和 EGFR 突变的肿瘤中，MUC5AC 的检出率较低（P=0.001）。值得注意的是，与纯黏液型相比，在产生黏液的非纯黏液型肺腺癌中，MUC5AC 具有更具侵袭性的行为、不同的表达模式，且与甲状腺转录因子 1 缺乏显著相关性（P=0.113）。MUC5AC 阳性肿瘤的预后明显差于 MUC5AC 阴性肿瘤（P<0.001）。多变量生存分析显示，MUC5AC 是预后不良的独立预后因素（P=0.006）。