Abstract 3325: EGFR mutation and protein expression analysis in sinonasal inverted papilloma and squamous cell carcinoma
Authors: Cabal Virginia N. , Menéndez Marta , Potes-Ares Sira , Vivanco Blanca , Suárez-Fernández Laura , Riobello Cristina , García-Marín Rocío , López Fernando , Llorente José Luís , Hermsen Mario 
Published: August 2019

Abstract
Introduction Inverted sinonasal papilloma has been demonstrated to be precursor to a subset of sinonasal squamous cell carcinoma and to carry frequent mutations in EGFR exon 20. The aim of this study was to evaluate EGFR mutation and protein expression as risk marker for malignant transformation of inverted papillomas.
Experimental procedures The total number of samples studied was 41 inverted papillomas (ISP) and 32 squamous carcinomas (SCC). We defined patients with one single ISP, with multiple ISP (ISP-ISP) or ISP with malignant transformation (ISP-transformed). In addition, we classified SCC related with ISP (SCC-ISP) and those without relation (SCC de novo). EGFR exon 20 was amplified by PCR and analyzed by Sanger sequencing using the ABI PRISM 3100 and 3730 Genetic Analyzer, (Applied Biosystems, Foster City CA). Immunohistochemistry was performed on an automatic staining workstation (Dako Autostainer Plus; DakoCytomation, Glostrup, Denmark) using the antibody anti-pEGFR clone D7A5 (Cell Signaling Technology, Cambridge, UK). Results were evaluated by two experienced investigators (BV and MM).
Results We found EGFR exon 20 mutations in 62% (8/13) ISP, 58% (7/12) ISP-ISP, 63% (10/16) ISP-transformed, 54% (7/13) SCC-ISP and 5% (1/19) SCC de novo. Protein expression of pEGFR was detected in 56% (5/9) ISP, 75% (6/8) ISP-ISP, 47% (7/15) ISP-transformed, 42% (5/12) SCC-ISP and 71% (10/14) SCC de novo. We observed an inverse correlation between EGFR exon 20 mutation and pEGFR expression (p=0.034). Overall survival was significantly better for SCC-ISP compared with SCC de novo (2-year survival 54% and 29% respectively; p=0.030).
Conclusions EGFR exon 20 mutations occurred in a high frequency, both for cases with single or multiple ISP and for ISP-transformed, making it a characterizing genetic abnormality for ISP in general. This result also means that the presence of a EGFR exon 20 mutations is not of value as a risk marker for malignant progression. Among the SCC, EGFR exon 20 mutations were notably less and pEGFR expression more frequent in SCC de novo compared to SCC-ISP, suggesting that the EGFR signaling pathway is important in both types of SCC, albeit activated in a different manner. Patients with SCC-ISP had a more favorable clinical course, however, neither EGFR exon 20 mutations nor pEGFR expression demonstrated prognostic value. Nevertheless, EGFR exon 20 mutations can be targeted with specific inhibitors and may be of value for adjuvant therapy for SCC as well as ISP that are difficult to manage.
Citation Format: Virginia N. Cabal, Marta Menéndez, Sira Potes-Ares, Blanca Vivanco, Laura Suárez-Fernández, Cristina Riobello, Rocío García-Marín, Fernando López, José Luís Llorente, Mario Hermsen. EGFR mutation and protein expression analysis in sinonasal inverted papilloma and squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3325.