Is availability of anti-EGFR therapy for the colorectal adenocarcinomas showing fascin expression limited?

Abstract

Colorectal adenocarcinoma (CRC) is a major cause of death. Fascin expression in CRCs was proved to be related with higher metastatic rates and poor prognosis, while metastatic patients with only wild type K-RAS gene are the candidates of recent molecularly targeted anti-epidermal growth factor receptor (EGFR) therapies. This study is designed to investigate the correlation between the fascin expression status and the K-RAS mutational status of CRCs in order to assess the availability rate of anti-EGFR therapies for patients with fascin-expressing CRCs. Immunohistochemical expression of fascin and mutational status of K-RAS were investigated in the archival materials of randomly selected 50 metastatic colorectal carcinoma patients. Strength of fascin expression and tumor percentage stained with fascin were scored semi quantitatively. c.34 > C (p.G12R), c.35 g > C (p.G12C), c.34G > A (p.G12S), c.35G > A (p.G12D), c.35G > T (p.G12V), c.35G > C (p.G12A), and c.38G > A (p.G13.D) mutations in K-RAS gene were studied by using RT-PCR. In immunohistochemical evaluation, 32 of the 50 cases stained positive with fascin, while 21 were positive for K-RAS mutations in codon 12 (10 patients) or in codon 13 (3 patients). The correlation between the positivity of fascin and the presence of K-RAS mutations, the strength of fascin staining and the presence of K-RAS mutations, and the tumor cell percentage stained with fascin and the presence of K-RAS mutations were found statistically significant. The results of this study suggest that patients with fascin-expressing CRCs have a greater tendency to carry an activating K-RAS mutation which will prevent them from taking targeted anti-EGFR therapies. Larger series are needed to confirm these results.