title: 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.
authors.affiliation: Department of Pathology, Başkent University Adana Research and Medical Center, Adana, Turkey, nemrahkocer@yahoo.com.
authors.forename: Nazım Emrah
authors.initials: NE
authors.lastname: Koçer
authors.forename: Fazilet
authors.initials: F
authors.lastname: Kayaselçuk
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000096:biosynthesis*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002352:Carrier Proteins; C502658:FSCN1 protein, human; C117307:KRAS protein, human; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab