Abstract
Therapies targeting EGFR are effective in treating tumors that harbor molecular alterations; however, there is heterogeneity in long-term response to these therapies. We retrospectively analyzed protein expression of EGFR, Stat3, phospho-Akt, and phospho-Erk1/2 by immunohistochemistry in a series of resected cases from a single institution, correlated with clinicopathological variables. There were 96 patients, with the majority of cases being of low stage tumors (17 pT1a, 23 pT1b, 30 pT2a, and 18 pT2b). Histologic subtypes were 45 acinar predominant, 2 cribriform, 25 solid, 7 papillary, 11 lepidic, and 4 mucinous tumors. The EGFR score was higher in tumors with vascular invasion (P = 0.013), in solid and cribriform acinar histology, and in high stage tumors (P = 0.006 and P = 0.01). EGFR was more likely overexpressed in solid compared to lepidic tumors (P = 0.02). Acinar tumors had the highest rate of ERK1/2 positivity (19%). There was a strong correlation among positivity for ERCC1 and other markers, including STAT3 (P = 0.003), Akt (P = 0.02), and ERK1/ERK2 (P = 0.0005). Expression of molecules downstream to EGFR varied from 12% to 31% of tumors; however, the expression did not directly correlate to EGFR expression, which may suggest activation of the cascades through different pathways. The correlation of protein expression and the new lung adenocarcinoma classification may help in the understanding of activated pathways of each tumor type, which may act in the oncogenesis and drug resistance of these tumors.
Highlights
Lung cancer is the leading cause of cancer death worldwide
There was a strong correlation among positivity for enzyme repair crosscomplementation group 1 (ERCC1) and other markers, including STAT3 (P = 0.003), Akt (P = 0.02), and ERK1/ERK2 (P = 0.0005)
Lung adenocarcinomas are the most common histologic subtype and are part of the larger group of nonsmall cell lung cancer (NSCLC) that has been target of a recent evolution on the chemotherapeutical regimens based on molecular profiling
Summary
Lung cancer is the leading cause of cancer death worldwide. Most lung patients present with advanced stage disease and are not candidates for curative surgery; genetargeted therapies offer hope for prolonged survival in advanced disease [1, 2]. A contemporary revolution in the treatment of nonsmall cell lung cancer (NSCLC) centers on biomarkers that predict who are more likely to respond to specific targeted therapies [3, 4] These biomarkers are typically assessed by protein overexpression evaluated by immunohistochemistry, gene copy number evaluated by in situ hybridization, or specific mutations studied by a variety of PCR methods. These studies have been used mainly as predictors of response to the EGFR tyrosine kinase inhibitors (TKIs) [5, 6]. Analyses of other molecular signatures and profiles in protein expression may be critical in understanding the development in effective new drugs and combinations [7,8,9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
