[2010] Mucin5B (MUC5B) Expression Correlates with High Stage in Lung Adenocarcinoma by Quantitative Proteomics and Immunohistochemistry

Gloria H Lewis, Yan Li, Frederic Askin, Edward Gabrielson, Hui Zhang, Qing Kay Li. The Johns Hopkins Medical Institutions, Baltimore, MD

Background: Pathogenesis of lung cancer is characterized by multiple genetic alterations and subsequent abnormal protein expression leading to phenotypic changes. EGFR mutation is well established in the pathogenesis of lung cancer. Recent studies have shown mucin (MUC) proteins (a group of over 20 heavily glycosylated, high molecular weight proteins) to play important roles in cancer differentiation, invasion, and metastasis in a variety of adenocarcinomas. Among them, the expression of MUC5B has been suggested in the EGFR signaling pathways in lung cancers; however, it is not well studied. We quantitatively analyzed protein expression in lung adenocarcinomas by a newly improved proteomic technique to identify potential biomarkers differentially expressed based on pathological stage. The expression of MUC5B by proteomics and immunohistochemistry (IHC) was then correlated with pathological stage.
Design: Formalin fixed paraffin-embedded tissue from 8 cases each of early (I/II) and late (III/IV) stage lung adenocarcinomas, and normal lung were quantized for expression of 370 proteins by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Tissue microarrays containing 51 cases of lung adenocarcinoma were stained for MUC5B by immunohistochemistry (IHC).
Results: Of the 370 proteins quantitatively analyzed by LC-MS/MS, 13 proteins, including MUC5B, were markedly elevated in stage III/IV compared to stage I/II and normal lung tissue (Table 1). By IHC, MUC5B was found to correlate with high stage (Table 2).

Table 1: Proteomics Data

Protein	Normal tissue*	Stage I/II*	Stage III/IV*
Alpha-depensin 1	0.187	0.686	0.867
Annexin A3	0.179	0.446	0.945
Azurocidin 1	0.081	0.508	1.311
G-6-P isomerase	0.528	0.985	3.421
Histone cluster 1	0.354	0.971	1.645
Histone H4	0.588	1.226	1.652
Lactotransferrin	0.217	0.471	1.151
Lysozyme	0.291	0.334	1.120
Mucin 5B	0.515	0.573	1.474
Myeloperoxidase	0.164	0.890	1.059
Plastin-2	0.295	0.562	1.668
S100-A8	0.163	0.382	1.023
Utrophin	0.143	0.429	1.387

*Ratio of relative peak area to internal standard

Table 2: MUC5B Expression by IHC

Tissue	MUC5B
Normal lung	0/6 (0%)
BAC, Stage I/II	34/44 (77.3%)
Stage III/IV	7/7 (100%)

Conclusions: Our data indicate that the expression of MUC5B is higher in stage III/IV than I/II lung adenocarcinomas, suggesting that MUC5B could be a predictor of tumor aggressiveness. Since aggressive cancers frequently present at high stage, future studies will evaluate whether MUC5B is useful for predicting tumor aggressiveness in early stage cancers.
Category: Pulmonary

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 311, Tuesday Afternoon