EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer
Vittoria Martin1, Elena Zanellato1, Alessandra Franzetti-Pellanda2, Francesca Molinari1, Alessandra Movilia3, Alessia Paganotti4, Letizia Deantonio5, Sara De Dosso2, Agnese Assi3, Stefano Crippa1, Renzo Boldorini4, Luca Mazzucchelli1, Piercarlo Saletti2 and Milo Frattini1
1Institute of Pathology, Locarno, Switzerland, 2Oncology Institute of Southern Switzerland, Bellinzona, Switzerland, 3Department of Pathology, Civil Hospital, Legnano, Italy, 4Department of Medical Sciences, University School of Medicine, Novara, Italy and 5Radiotherapy Unit, University School of Medicine, Novara, Italy
*Clinica Luganese, Lugano, Switzerland
Offprint requests to: Dr. Vittoria Martin, Institute of Pathology, Via in Selva 24, 6600 Locarno, Switzerland. e-mail: vittoria.martin@ti.ch
Summary. Background: Combined chemoradiation therapy is the gold standard in the treatment of squamous cell anal cancer (SCAC). However, even if the response rate is very high, many patients eventually relapse or experience a recurrence, thus requiring an invasive surgical procedure that has severe side effects. Most SCAC tumors overexpress epidermal growth factor receptor (EGFR); therefore, it is reasonable to consider anti-EGFR drugs as a new treatment option, as demonstrated by anecdotal reports. Promising results obtained in other solid tumors, both squamous and non-squamous, have revealed that an increase in the EGFR gene copy number may predict the efficacy of anti-EGFR therapies, while the presence of mutations in downstream members of the EGFR pathway may confer resistance. These markers have been only sporadically considered in SCAC.
Methods: We investigated the status of the EGFR gene using FISH and examined KRAS, BRAF, and PIK3CA hot-spots mutations using sequencing analysis in a cohort of 84 patients affected by SCAC.
Results: Twenty-eight patients (34%) showed an increase in EGFR gene copy number due to amplification (4%) or to polysomy (30%). KRAS and PIK3CA gene mutations were found in 4 (5%) and 13 patients (16%), respectively. No mutations were found in the BRAF gene.
Conclusions: The characterization of the EGFR pathway may help in identifying different subgroups of SCAC that have specific molecular features, which may have implications in what targeted therapies are used to treat each patient. Histol Histopathol 29, 513-521 (2014)
Key words: Squamous Cell Anal Cancer, EGFR, KRAS, PIK3CA, EGFR-targeted therapy
DOI: 10.14670/HH-29.10.513