Abstract 4666: Profiling mesothelin protein expression by immunohistochemistry and gene expression in adenocarcinoma and squamous cell carcinoma of lung
Authors: Wong Jackson , Gaffney Dana , Sharp Michael , Hertzog Brenda , Karkera Jayaprakash , Platero Suso , Alvarez John 
Published: May 2015

Mesothelin is a 40 kDa secreted glycoprotein expressed in normal mesothelial cells and over-expressed in several histological types of tumors. Detection of mesothelin by immunohistochemistry (IHC) may assist in the diagnosis of mesothelioma. Mesotheliomas are positive for mesothelin staining, but carcinomas of the lung may also be positive for this marker. Mesothelin positivity in adenocarcinoma of the lung reportedly ranges from 22% to 71% of cases depending upon the specific subtype. Mesothelin positivity in squamous cell carcinomas (SCC) of lung is reported to be 16% in non-keratinizing and 31% in keratinizing subtypes. We performed mesothelin IHC on a cohort of 50 lung carcinoma samples (16 adenocarcinomas and 34 SCC). Mesothelin expression was observed in 10 out of 16 (62.5%) lung adenocarcinoma samples, of which 8 showed greater than 10% of tumor cells with positive membrane staining of any intensity. Mesothelin expression was observed in 19 out of 34 (55.9%) lung SCC samples, of which only 3 samples showed greater than 10% of tumor cells with positive membrane staining of any intensity. These findings are in concordance with previous reports which show a higher prevalence of mesothelin protein expression in lung adenocarcinoma than in lung SCC. To correlate RNA expression with protein expression, we performed gene expression profiling on a subcohort of these lung cancer specimens. Out of 50 lung carcinoma samples, 28 samples (10 adenocarcinomas and 18 SCCs) provided adequate RNA yield for gene expression profiling for mesothelin. A total mean relative gene expression (mRGE) value of 13.64 with a standard deviation (SD) of ±3.71 was obtained for the adenocarcinoma samples and a mRGE value of 14.78 with a SD of 2.64 was obtained for the SCC samples. We next arbitrarily assigned samples with greater than 10% mesothelin stained cells as “positive” and the remainder as “negative”. Six negative adenocarcinoma samples yielded a mRGE value of 12.98 with a SD of ±3.84, and four positive adenocarcinoma samples yielded a mRGE value of 14.63 with SD of ±3.82. Sixteen negative SCC samples resulted in a mRGE 14.63 with SD of ± 2.75 and two positive SCC samples yielded a mRGE of 15.98 with a SD of ±1.37. There was no apparent correlation between mRGE values and IHC positivity. We also correlated gene expression with p53 mutation status. Sixteen wild type samples, composed of equal number of adenocarcinoma and SSC had a total mRGE of 14.29 with SD of ±3.32. Seven samples with p53 mutations had a total mRGE of 16.09 with SD ±1.93. These data indicate that mesothelin gene expression is not associated with p53 mutation status. Future studies with an increased number of samples may yield significant associations between protein expression, gene expression and mutation status.

Citation Format: Jackson Wong, Dana Gaffney, Michael Sharp, Brenda Hertzog, Jayaprakash Karkera, Suso Platero, John Alvarez. Profiling mesothelin protein expression by immunohistochemistry and gene expression in adenocarcinoma and squamous cell carcinoma of lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4666. doi:10.1158/1538-7445.AM2014-4666