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.

Sequencing of mutational hotspots in cancer-related genes in small cell neuroendocrine cervical cancer

“…Mutations in PIK3CA are also commonly found in other HPV-associated malignancies, such as oropharyngeal cancer (28%)[13] and squamous cell anal cancer (22%). [14]…”

No evidence of NRAS mutation in squamous cell anal carcinoma (SCAC)

“…Forty-eight patients received the Nigro scheme with standard dosages19, while the remaining 2 patients underwent treatment with cisplatin plus 5-fluorouracil. This case series was previously characterized by our group for HPV infection, KRAS (exons 2–4), BRAF (exons 11 and 15) and PIK3CA (exons 9 and 20) status15.…”

“…Genomic DNA was extracted from Formalin-fixed paraffin-embedded (FFPE) tumor blocks, as previously described15. NRAS (exons 2, 3 and 4) status was analyzed by Pyrosequencing using anti-EGFR MoAb response ( NRAS status) (Diatech, Jesi, Ancona, Italy), according to the manufacturer’s instructions.…”

“…KRAS mutation seems to be a rare event in SCAC. Some studies, including a study from our group, have shown that no KRAS mutation is present in SCAC4561516, whereas others have reported rates of KRAS mutation of 1–5%1718. A low frequency of BRAF mutations has also been observed in SCAC, with a rate of 0–5%151718.…”

“…A low frequency of BRAF mutations has also been observed in SCAC, with a rate of 0–5%151718. A higher rate of PIK3CA mutation between 16% and 22%, has been observed1518. However, no correlation with patient prognosis was observed for these mutations, as well as for HPV infection.…”