Expression of the epidermal growth factor receptor (EGFR) pathway in cervical cancer (CC) patients (pts)

Abstract

5519 Background: EGFR, a membrane tyrosine kinase receptor that regulates multiple functions such as cell growth, differentiation, gene expression and development through at least 3 pathways, is overexpressed in a wide variety of solid tumors, including CC. The downstream activation of the EGFR pathways has not been studied extensively. The aim of this study is to assess the correlation between EGFR-HER-2-HER-3-HER-4 status, downstream pathways (STAT 3, survivin, RAS) with pt characteristics, overall survival and recurrence free survival in pts diagnosed with invasive CC. Methods: Receptor expressions were assessed by immunohistochemistry on 80 pts from our clinic. Tumors were scored by percentage of cells stained multiplied by intensity for a score range of 0–300 by two pathologists. Median EGFR score was 140. Pts were categorized as low expressor (EGFR score lower than 140) or as high expressor (EGFR score greater than 140). Differences in receptor expression were compared using the Log-rank test for overall (OS) and recurrence-free survivals (RFS) and by Chi-square analyses for the clinical parameters (age, stage, histology, and grade). Results: A total of 80 pts data was analyzed. Mean age of the sample was 48 years. 23% of pts had well differentiated tumors. 80% had squamous histology. 39% had stage IIB or higher. 25% died of cancer. By Log-rank test, standard prognostic factors (age, stage, grade, and histology) showed the expected differences in survival, confirming the validity of the sample. However there were no correlations between the clinical parameters, OS, or RFS with EGFR expression. Data on HER-2–3-4, STAT3, survivin and RAS will be presented at the meeting. Conclusions: Although no correlation has been found between clinical outcome and EGFR expression, EGFR inhibitors of the extracellular domain are expected to be useful for the treatment of CC that overexpress this receptor. These results will serve as baseline data needed to test cetuximab and other EGFR inhibitors in pts with CC. No significant financial relationships to disclose.

Identification of High-Risk Human Papillomavirus (hrHPV)-Associated Genes in Early Stage Cervical Squamous Cell Carcinomas

“…The EGFR gene, which encodes the epidermal growth factor receptor, a potent stimulator of the mitogen-activated protein kinase signalling pathway, seems to play a role in the development of cervical cancer. 45 Higher EGFR expression has been reported in primary CSCC than in normal cervical mucosa. 46 Moreover, EGFR over-expression was shown to be a predictor of tumour aggressiveness and invasiveness in CSCC.…”

“…8 Over 150 types of HPV are known to exist and some sources indicate that there are more than 200 subtypes. 9 -11 Of these, 15 are classified as high-risk (16,18,31,33,35,39,45,51,52,56,58,59, 68, 73 and 82), three as probable high-risk (26, 53 and 66) and 12 as low-risk (6,11,40,42,43,44,54,61,70,72, 81 and CP6108) types, 12 although even the low-risk types may cause cancer. Types 16, 18 and 31 are generally acknowledged to cause nearly 70% of cervical carcinoma cases and they are the prime risk factors for cervical carcinoma.…”

“…46 Moreover, EGFR over-expression was shown to be a predictor of tumour aggressiveness and invasiveness in CSCC. 45,47 Experimental studies have demonstrated that HPV infection elevates EGFR levels by posttranslational mechanisms in keratinocytes. 48 The transforming activity of high-risk HPVs, particularly well studied in HPV16 and HPV18, seems to depend mainly on the expression of E6 and E7 HPV oncoproteins and on their ability to interact with some cell components (such as p53 and pRb) and alter cell cycle control mechanisms.…”