Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

Abstract

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I -IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P ¼ 0.001) and perinuclear (p)CA IX (P ¼ 0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (Po0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (Po0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P ¼ 0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number ¼ 21); group 2 had no expression of EGFR (number ¼ 75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number ¼ 70). Group 3 had a worse prognosis than either groups 1 or 2 (P ¼ 0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P ¼ 0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies.

Analysis of c-ErbB1/Epidermal Growth Factor Receptor and c-ErbB2/HER-2 Expression in Bronchial Dysplasia: Evaluation of Potential Targets for Chemoprevention of Lung Cancer

“…Increased expression of EGFR has been shown in the majority of non -small cell lung cancers with overexpression in up to 85% of squamous cell lung carcinomas (23 -27). In some studies, EGFR overexpression has also been shown to have prognostic implications in lung cancer (28,29), whereas, in others, including studies from our institution, no significant association with prognosis was found (26). Bronchial dysplasia is believed to be the precursor of squamous cell lung carcinoma; thus, EGFR might play a significant role in the progression of these lesions to invasive cancer.…”

Modification of the Primary Tumor Microenvironment by Transforming Growth Factor α-Epidermal Growth Factor Receptor Signaling Promotes Metastasis in an Orthotopic Colon Cancer Model

“…10 Aberrant expression of TGF␣ or EGFR by tumors typically confers a more aggressive phenotype and is thus often predictive of poor prognosis. [11][12][13][14] Supported in part by SPORE in Prostate Cancer grant CA902701 from the National Cancer Institute.…”

The relationship between EGFR gain and VHL loss in lung adenocarcinoma and poor patient survival

“…Overexpression of EGFR has been correlated with the poor prognosis of NSCLCs [23,24]. In the present study, we observed for the first time that EGFR gene copy number gain was independently associated with poor patient survival of lung adenocarcinoma.…”