Extensive Characterization of EGFR Pathways May Help in Integrating the Use of EGFR-Targeted Therapies in Patients with Squamous Cell Anal Cancer.
Vittoria Martin, Elena Zanellato, Francesca Molinari, Stefano Crippa, Massimo Bongiovanni, Sara De Dosso, Alessandra Franzetti-Pellanda, Alessandra Movilia, Agnese Assi, Renzo Boldorini, Alessia Paganotti, Letizia Deantonio, Luca Mazzucchelli, Piercarlo Saletti, Milo Frattini. Institute of Pathology, Locarno, Switzerland; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Civil Hospital, Legnano (MI), Italy; University School of Medicine, Novara, Italy
Background: Chemo-radiation is the standard treatment for local squamous cell anal cancer (SCAC). In locally advanced head and neck squamous cell carcinomas, monoclonal antibodies (MoAbs) targeting EGFR have proven to improve survival in combination with radiotherapy. In colorectal cancer, patients benefit from anti-EGFR MoAbs in presence of EGFR gene copy number gain (CNG) and absence of mutations in EGFR downstream members (except for PIK3CA exon 9 mutations).
Design: We described alterations of EGFR pathway in SCAC biopsies, to evaluate whether anti-EGFR MoAbs can be integrated in the management of this condition. Thirty-five SCAC biopsies were collected in the Departments of Pathology in Locarno, Legnano and Novara. EGFR gene status was assessed by fluorescent in-situ hybridization, whilst K-Ras, BRAF and PIK3CA mutations by direct sequencing.
Results: EGFR CNG was observed in 5 cases (20%). No BRAF mutations were detected. K-Ras was mutated in 1 case (3%, G12V change), PIK3CA in 8 cases (23%, 6 changes in exon 9 and 2 in exon 20). EGFR CNG was concomitant either to K-Ras or to PIK3CA exon 9 mutations (in 1 case each). The 3 remaining EGFR CNG cases did not show any other EGFR downstream signal alterations. Overall 4 out of 36 SCAC patients (11%) might have a proficient pattern for anti-EGFR MoAbs treatment
Conclusions: EGFR gene deregulation, K-Ras and PIK3CA mutations are involved in SCAC carcinogenesis. Our results suggest a possible role of EGFR-targeted agents in integrated treatment of SCAC, and clinical trials involving anti-EGFR MoAbs in this disease should consider an early analysis of these factors to identify patients who might benefit from these drugs.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 57, Wednesday Morning