EGFR Expression and KRAS and BRAF Mutational Status in Intestinal-Type Sinonasal Adenocarcinoma
Vanessa Szablewski, Jerome Solassol, Louis Crampette, Marion Larieux, Ariane Tempier, Valerie Costes. CHU Montpellier, Montpellier, France
Background: Intestinal-type adenocarcinoma (ITACs) of the nasal cavity and paranasal sinuses are rare and aggressive tumor, with an estimated 5-year survival of 40%. Interestingly these tumors show morphologic and phenotypic features that are usually indistinguishable from colorectal cancer (CRC). These resemblances make reasonable to foresee that both tumor types may share equivalent genetic alterations. Since KRAS and BRAF mutations could be negative predictive factors for anti-EGFR therapies in CRC, we sought to determine the incidence of KRAS and BRAF mutations in ITACs. In addition we determine the prognostic impact of both KRAS/BRAF mutations and epidermal growth factor receptor (EGFR) expression and their potential association with clinicopathological features of ITACs.
Design: Paraffin embedded tumor samples of 43 ITACs were analyzed for KRAS exon 2 and BRAF exon 15 mutations and for EGFR expression through immunohistochemistry. Patients' information was extracted from medical records.
Results: 27 tumors (63%) showed EGFR positivity and 30% exhibited high expression level (+2/+3). KRAS mutations (p.G12D, p.G12C, p.G13D) were detected in 21 cases (48.8%). BRAF mutation (p.V600E) was identified in 3 specimens (6.1%). Using multivariate analysis, EGFR expression (+1, +2, +3) was significantly correlated with stage (p<0.001) and histotypes (p<0.001). No correlation was found with clinico-pathological parameters and KRAS and BRAF mutational status. Finally, no significant correlation was found in the disease free and overall survival between tumors with or without KRAS and BRAF mutations and EGFR expression.
Conclusions: Our data confirm the morphologic and phenotypic similarities at the genetic level between CRC and ITACs showing deregulation of KRAS/ BRAF and EGFR. No significant differences have been observed in clinico-pathological based on KRAS/ BRAF genotype and no prognostic value of KRAS/BRAF mutations were found. Despite multimodality treatment including surgery, radiotherapy and chemotherapy, ITACs show poor survival and new therapeutic approached are needed to improve this prognostic. A possibility may be offered by anti-EGFR therapies that have been developed in CRC. Our results indicate that KRAS mutations and EGFR expression are frequent in ITACs. So that EGFR directed molecular treatment could be investigated in a subset of patients affected by ITACs and KRAS mutation analysis could be used to preclude patients from receiving such treatment.
Category: Head & Neck
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 138, Tuesday Morning