title: KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC).
abstract: 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.
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Casadei Gardini
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Capelli
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ulivi
authors.affiliation: Radiotherapy Unit, Macerata Hospital, Macerata, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Giannini
authors.affiliation: Oncology Unit, Degli Infermi Hospital, Faenza, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Freier
authors.affiliation: Oncology Unit, Degli Infermi Hospital, Faenza, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Alassandro
authors.initials: A
authors.lastname: Passardi
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Ragazzini
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D001369:Axons; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005720:Gamma Rays; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D009154:Mutation; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000628:therapy; 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); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016685:Mitomycin; 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; D005472:Fluorouracil