Evaluation of EGFR abnormalities in patients with pulmonary adenocarcinoma: the need to test neoplasms with more than one method

Abstract

Patients with advanced pulmonary adenocarcinoma exhibiting overexpression or mutation of epidermal growth factor receptor tend to respond better to targeted therapy with tyrosine kinase inhibitors such as gefitinib and erlotinib. There is no consensus regarding how these neoplasms should be routinely tested for epidermal growth factor receptor (EGFR) and whether the results of immunohistochemistry (IHC), mutation analysis and fluorescent in situ hybridization correlate with each other or are independent predictive variables. We tested 100 pulmonary adenocarcinomas from patients with stage III or IV disease for EGFR abnormalities using IHC, PCR and fluorescent in situ hybridization (FISH) and compared the results using j and other statistical methods. The sensitivity of each test to detect an EGFR abnormality and its negative predictive value to estimate the presence of an abnormal test result by the other two methods were calculated. Abnormal EGFR test results were found in 62, 40 and 24% by IHC, FISH and PCR, respectively. j statistics yielded poor concordance between the results of the EGFR tests (j ¼ 0.3, and 0.2 for IHC and PCR and for PCR and FISH, respectively). Strong membranous immunoreactivity in more than 90% of the tumor cells was found to correlate with amplification or polysomy. PCR when used as a single test is likely to underestimate the presence of EGFR abnormalities that may significantly predict response to tyrosine kinase inhibitors. The need to standardize the approach to EGFR testing in patients with advanced pulmonary adenocarcinoma is discussed. Keywords: adenocarcinoma; EGFR; overexpression; amplification; polysomy Lung cancer is the most frequent cause of cancerrelated deaths with less than 15% 5-year survival.

High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer

“…Such selection of patients with NSCLC promoted a better treatment strategy for both high and low EGFR mutations abundant tumors. [30][31][32][33] Further quantification of staining scores in mutation-positive NSCLC has been assessed, and high staining score has been associated with a significant longer progression-free survival in mutation-positive patients as compared with low staining score. 31 A study in which the randomization to EGFR tyrosine kinase inhibitors would be based on the method used for demonstrating an activating EGFR mutation might give clinical relevant information regarding the significance of the amount of EGFR-mutated cells.…”

A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas

“…40 The lack of gene amplification does not entirely exclude the role of EGFR inhibitors in the treatment of metastasizing adnexal carcinomas; as there are conflicting results in the literature regarding the role of IHC, FISH, and/or PCR in treatment decision of various tumors. [41][42][43] There is frequent discrepancy between the EGFR protein expression and gene amplification in other tumors in the literature. 44 Furthermore, inconsistent results have also been reported regarding the correlation between EGFR gene mutations and EGFR gene amplification/ polysomy detected by FISH (Bell et al, 2005;Sone et al, 2005).…”

“…44 Furthermore, inconsistent results have also been reported regarding the correlation between EGFR gene mutations and EGFR gene amplification/ polysomy detected by FISH (Bell et al, 2005;Sone et al, 2005). In a recent series of 100 patients with advanced pulmonary adenocarcinoma, Gupta et al 41 proposed that tumors should be evaluated by more than one method to identify patients that may benefit from tyrosine kinase inhibitors therapy.…”

Overexpression of EGFR Protein in Bruneian Lung Cancer Patients

“…Previous studies have reported a correlation between levels of EGFR protein expression and gene mutation with poor prognosis and reduced survival rates of lung cancer (Sanja et al, 2006;Ekrem et al, 2010). In non-small cell lung cancer, overexpression of EGFR or mutations in intracellular EGFR have been observed in 43-89% of cases (Gupta et al, 2009). These mutations occur within EGFR exons 18-21 (Soh et al, 2009;Baek et al, 2014).…”