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Lung Adenocarcinoma With MUC4 Expression Is Associated With Smoking Status, HER2 Protein Expression, and Poor Prognosis: Clinicopathologic Analysis of 338 Cases.
- Source :
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Clinical lung cancer [Clin Lung Cancer] 2017 Jul; Vol. 18 (4), pp. e273-e281. Date of Electronic Publication: 2016 Dec 02. - Publication Year :
- 2017
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Abstract
- Background: MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers.<br />Patients and Methods: Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status.<br />Results: Ninety-four tumors (27.8%) were MUC4 positive. Most patients with MUC4-positive tumors were male (P < .001) and smokers (P = .006). Moreover, MUC4 expression was significantly associated with solid ADCs (P < .001) and vascular invasion (P = .001). MUC4 expression inversely correlated with TTF-1 expression (P = .020) and EGFR mutations (P = .004). Interestingly, MUC4 expression correlated with HER2 protein expression (P = .042), although MUC4 expression did not correlate with HER2 DNA amplification or HER2 gene mutations. Patients with MUC4-positive tumors had significantly worse prognoses compared to patients with MUC4-negative tumors (P = .025).<br />Conclusion: The present study showed that MUC4-positive lung ADCs correlated with male smokers, solid ADCs, negative TTF-1 expression, the EGFR wild-type gene, HER2 protein expression, and poorer prognoses. These results suggest that MUC4-positive lung ADC may be a distinct subtype found in patients with smoking-related poor outcomes, mediated by HER2 signaling pathway.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Adenocarcinoma diagnosis
Adenocarcinoma of Lung
Cigarette Smoking
ErbB Receptors genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Lung Neoplasms diagnosis
Male
Mutation genetics
Neoplasm Staging
Prognosis
Receptor, ErbB-2 metabolism
Sex Factors
Signal Transduction
Thyroid Nuclear Factor 1 genetics
Thyroid Nuclear Factor 1 metabolism
Tissue Array Analysis
Adenocarcinoma metabolism
Lung Neoplasms metabolism
Mucin-4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1938-0690
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Clinical lung cancer
- Publication Type :
- Academic Journal
- Accession number :
- 28065467
- Full Text :
- https://doi.org/10.1016/j.cllc.2016.11.013