KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC)

• Published in: PloS one 2014-03, Vol.9 (3), p.e92071
• Main Authors: Casadei Gardini, Andrea, Capelli, Laura, Ulivi, Paola, Giannini, Massimo, Freier, Eva, Tamberi, Stefano, Scarpi, Emanuela, Passardi, Alassandro, Zoli, Wainer, Ragazzini, Angela, Amadori, Dino, Frassineti, Giovanni Luca
• Format: Article
• Language: English
• Subjects: Aged; Anal cancer; Analysis; Antineoplastic Agents - therapeutic use; Anus; Anus Neoplasms - complications; Anus Neoplasms - genetics; Anus Neoplasms - pathology; Anus Neoplasms - therapy; Axons; Biology and Life Sciences; Cancer; Cancer research; Cancer therapies; Carcinogenesis; Carcinogens; Carcinoma; Carcinoma, Squamous Cell - complications; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Care and treatment; Class I Phosphatidylinositol 3-Kinases; Colorectal cancer; Deoxyribonucleic acid; Development and progression; DNA; DNA Mutational Analysis; Epidermal growth factor receptors; Female; Fluorouracil - therapeutic use; Gamma Rays; Genes; Genetic aspects; HIV; Human immunodeficiency virus; Human papillomavirus; Human papillomavirus 16 - isolation & purification; Humans; K-Ras protein; Male; Medicine and Health Sciences; Metastasis; Middle Aged; Mitomycin - therapeutic use; Mutation; Neoplasm Staging; Oncology; Papillomavirus infections; Papillomavirus Infections - complications; Papillomavirus Infections - genetics; Papillomavirus Infections - pathology; Papillomavirus Infections - therapy; Paraffin; Patients; Phosphatidylinositol 3-Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); Radiation therapy; ras Proteins - genetics; Research and Analysis Methods; Retrospective Studies; Studies; Surgery; Therapeutic applications; Therapy; Tumors; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092071

Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of the principal mechanism of resistance to this type of therapy. However, no information is available from the literature regarding the status of BRAF or PIK3CA in this cancer type. We analysed KRAS, BRAF and PIK3CA status in SCAC patients in relation to the clinical-pathological characteristics of patients and to the presence of the human papilloma virus (HPV). One hundred and three patients were treated with the Nigro scheme for anal cancer from March 2001 to August 2012. Fifty patients were considered for the study as there was insufficient paraffin-embedded tumour tissue to perform molecular analysis the remaining 53. DNA was extracted from paraffin-embedded sections. KRAS, BRAF and PIK3CA gene status and HPV genotype were evaluated by pyrosequencing. KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene was found to be mutated in 11 (22%) cases. In particular, 8 mutations occurred in exon 9 and 3 in exon 20 of the PIK3CA gene. These findings suggest that SCAC could potentially respond to an anti-EGFR drug. PIK3CA mutation may be involved in the process of carcinogenesis in some cases of SCAC.