Expression of EGFR and Molecules Downstream to PI3K/Akt, Raf-1-MEK-1-MAP (Erk1/2), and JAK (STAT3) Pathways in Invasive Lung Adenocarcinomas Resected at a Single Institution

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.

Activation of Janus kinase 1 confers poor prognosis in patients with non-small cell lung cancer

“…A previous study by the present authors and studies by others have indicated that inhibition of JAK signaling exhibits anticancer and anti-angiogenetic effects in human cancer lines and xenograft tumors, including lung cancer ( 13 , 23 – 25 ). These results support the hypothesis that JAK1 activation is important for tumorigenesis in NSCLC.…”

<p>Emodin sensitizes human pancreatic cancer cells to EGFR inhibitor through suppressing Stat3 signaling pathway</p>

“…EGFR belongs to the tyrosine kinase receptor (RTK) family, and over-activation of EGFR promotes the cascade response of downstream signaling pathways, including Ras/Raf/MEK/ERK, PI3K-AKT and JAK/STAT. 30,31 This leads to the occurrence and metastasis of the tumor. EGFR inhibitors have been widely used in clinical oncology treatment, but their toxic side effects and drug resistance have greatly limited their application.…”

Effect of cell‐phone radiofrequency on angiogenesis and cell invasion in human head and neck cancer cells

“…RF, radiofrequency [Color figure can be viewed at wileyonlinelibrary.com] cancer progression via the stimulation of cell proliferation, cell invasion, and angiogenesis. [14][15][16] Thus, Erk1/Erk2 activation was evaluated in FaDu and SCC25 cell lines exposed to cell-phone radiofrequency in comparison with their unexposed control cells. We found that Erk1/Erk2 is activated, under the effect of cell-phone radiofrequency, in both cell lines in comparison to their control ( Figure 4A,B).…”