EGFR family and cMet expression profiles and prognostic significance in esophagogastric adenocarcinoma

Abstract

Background: Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA. and cMet expression scored as low (0, 1+) or high (2+, 3+). Demographic and tumor characteristics were compared using Fisher exact test. Kaplan-Meier curves and univariate analysis compared survival among different receptors. Results: Total 52 patients were included in the study with median age 66 years. High expression of EGFR (73%), HER2 (40%), HER3 (75%), HER4 (35%) and cMet (69%) was detected among the study group. HER3 and HER4 co-expression was found in 18 (35%) cases. Pan expression of all four EGFR family members with cMet was noted in only 17% of cases. On univariate analysis, tumor stage and depth correlated with survival, while cMet + HER3 +/-EGFR receptor co-expression trended towards a worse survival. Conclusions: EGFR family and cMet are frequently co-expressed in treatment naïve resected EGA or GEJ tumors. Although our data do not significantly show receptor status as a prognostic factor, the co-expression profiles support for further investigation to improve targeting of this signal transduction axis.

Identifying Biomarkers in Lymph Node Metastases of Esophageal Adenocarcinoma for Tumor-Targeted Imaging

“…However, another study reported a higher VEGF expression rate in tumor and background tissue, as corroborated by our results [17]. Chan et al [18] studied the IHC expression of EGFR, HER-2, and c-MET in patients with EAC and reported a higher expression of these markers than that in our results; however, this study included only patients with early disease and primary surgery. HER-2 has been often studied in esophageal cancer for treatment with trastuzumab [18].…”

“…Chan et al [18] studied the IHC expression of EGFR, HER-2, and c-MET in patients with EAC and reported a higher expression of these markers than that in our results; however, this study included only patients with early disease and primary surgery. HER-2 has been often studied in esophageal cancer for treatment with trastuzumab [18]. A systematic review of nine studies reported a pooled expression of 25% (146 of 573 patients) for HER-2 in EAC, but this meta-analysis revealed large differences in results between studies [19].…”

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

“…EGFR signaling can involve a number of intracellular molecules such as extracellular signal-regulated kinase (ERK), cyclin D1 and β-catenin [51]. The presence of EGFR is detected in a wide range of cancer types (Table 3 [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77]). Normally, the EGFR gene is located on chromosome 7.…”

Relationship between 18F-fluorodeoxyglucose PET/computed tomography metabolic parameters and clinicopathology in endometrial cancer

“…c-Met staining was scored using a four-step scale: negative (0), weak (1+), moderate (2+), and strong (3+) positivity. If tumor cells stained moderately or strongly positive in more than 30% of tumor cells were considered to be positive [15,16]. The histopathological results were reviewed by two experienced pathologists.…”