title: EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer.
abstract: 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 reccurrence, 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute of Pathology, Locarno, Switzerland. vittoria.martin@ti.ch.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Martin
authors.affiliation: Institute of Pathology, Locarno, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Zanellato
authors.affiliation: Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzetti-Pellanda
authors.affiliation: Institute of Pathology, Locarno, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Molinari
authors.affiliation: Department of Pathology, Civil Hospital, Legnano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Movilia
authors.affiliation: Department of Medical Sciences, University School of Medicine, Novara, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Paganotti
authors.affiliation: Radiotherapy Unit, University School of Medicine, Novara, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Deantonio
authors.affiliation: Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: De Dosso
authors.affiliation: Department of Pathology, Civil Hospital, Legnano, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Assi
authors.affiliation: Institute of Pathology, Locarno, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Crippa
authors.affiliation: Department of Medical Sciences, University School of Medicine, Novara, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.affiliation: Institute of Pathology, Locarno, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Mazzucchelli
authors.affiliation: Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Saletti
authors.affiliation: Institute of Pathology, Locarno, Switzerland.
authors.forename: Milo
authors.initials: M
authors.lastname: Frattini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins