Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer

Abstract

We examined the potential of quantitative epidermal growth factor receptor (EGFR, synonym: c-erbB-1) and c-erbB-2 (synonym: HER2/neu) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy), followed by radical surgical resection, in patients with oesophageal cancer. Tissue samples were collected by endoscopic biopsy prior to treatment. RNA was isolated from biopsies and quantitative real-time reverse transcriptase -polymerase chain reaction assays were performed to determine c-erbB-1 and c-erbB-2 mRNA expression. Relative expression (tumour/paired normal tissue ratio standardised for b-actin) was calculated for EGFR and c-erbB-2 mRNA. Expression levels were correlated with the objective histopathologic response in resected specimens. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumour cells, or in case a pathologically complete response was achieved. Expression of c-erbB-1 mRNA was not associated with the degree of histomorphological response. In contrast, the relative expression levels of c-erbB-2 mRNA 41 were not associated with major histopathologic responses (sensitivity 41.6%, specificity 100%), and 10 out of 36 (28%) patients could be unequivocally identified, whose tumours did not respond well to the delivered neoadjuvant radiochemotherapy (Po0.01). Quantitative expression levels of c-erbB-2, but not c-erbB-1 mRNA, in pretreatment biopsies appear to predict minor histopathologic response to our neoadjuvant radiochemotherapy protocol. This test could be used to prevent expensive, noneffective and potentially harmful therapies in approximately one-fourth of our patients, and leads to a more individualised type of combined modality treatment.

The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus

“…Thus, whereas some studies have indicated that p53 gene mutation and/or p53 protein accumulation in tumour cells may be significantly associated with resistance to multimodal therapy and/or poor survival (Seitz et al, 1995;Ribeiro et al, 1998;Sarbia et al, 1998;Krasna et al, 1999;Gibson et al, 2003), others have not found such a correlation (Soontrapornchai et al, 1999;Ito et al, 2001;Shimada et al, 2002;Pühringer-Oppermann et al, 2006). With regard to EGFR, two studies indicated that tumours with strong EGFR expression show a relatively poor response to chemoradiotherapy (Hickey et al, 1994;Gibson et al, 2003), whereas another study did not find such a correlation (Miyazono et al, 2004). Moreover, in one of the two positive studies (Gibson et al, 2003), EGFR was found to have predictive value in oesophageal adenocarcinoma, but not in squamous cell carcinoma.…”

Predicting Response to Treatment in Gastroesophageal Junction Adenocarcinomas: Combining Clinical, Imaging, and Molecular Biomarkers

“…In particular, studies based on examination of specific pathways and approaches have so far failed to provide a molecular basis for the greater uptake of 18 FDG in tumors and the decrease that characterizes early metabolic response to therapy. Table 4 summarizes the studies that have demonstrated the predictive value of a number of molecular biomarkers in as- [60] continued 278 Predicting Response in GEJ Adenocarcinoma sessing histopathological response/survival in GEJ cancer patients with neoadjuvant therapy [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. None of the biomarkers available have been prospectively tested, and most studies are on small patient populations.…”

Reply: Her2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma of oesophagus?

“…We totally agree with them about the fact that several analyses of HER2 carried out by immunohistochemistry or other methods (Shiga et al, 1993;Hardwick et al, 1997;Tanaka et al, 1997;Friess et al, 1999;Wang et al, 1999;Akatmatsu et al, 2003;Miyazono et al, 2004;Mimura et al, 2005a, b;Sato et al, 2005;Sunpaweravong et al, 2005) have all found rates of overexpression greater than 2.8%. To our opinion, the differences observed between these different studies have several origins: the first of them, as clearly said by Khan and coworkers is the high heterogeneity in the methodologies used in the collection of studies cited by these authors.…”