Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing.

Shinichiro Yasukawa,Takayoshi Suzuki,Dai Takagi,Takatsugu Mizumachi,Satoshi Kano,Akira Nakazono,Yuji Nakamaru,Hiroshi Nishihara,Shinya Tanaka,Akihiro Homma,Hiromitsu Hatakeyama,Masanobu Suzuki

doi:10.1007/s10147-018-1296-1

Abstract

The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated. To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing. The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene. Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.

Highlights

Sinonasal papilloma accounts for 0.4-4.7% of all nasal tumors and is histopathologically classified into three types: inverted papilloma (IP), exophytic papilloma and oncocytic papilloma.[1]
We selected 29 patients with IP or squamous cell carcinoma (SCC) involving the nasal or paranasal sinus who were treated at Hokkaido University Hospital between 2007 and
The number of mutant genes increased in the order of IP

Summary

Introduction

Sinonasal papilloma accounts for 0.4-4.7% of all nasal tumors and is histopathologically classified into three types: inverted papilloma (IP), exophytic papilloma and oncocytic papilloma.[1]. The standard treatment for IP is complete resection. It is impossible to completely diagnose the malignant transformation of IP by macroscopic findings and computed tomography (CT). Most of the malignant tissues present as squamous cell carcinoma (SCC). SCC within IP has been reported to occupy 10 to 95% of the total tumor volume.[7] a preoperative biopsy may not include areas of the IP showing malignant change and, is not always effective in assisting the clinician in reaching a correct diagnosis. Multiple preoperative biopsies from different sites within the tumor tissue may be necessary to prevent misdiagnosis. The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated

Methods

Results

Conclusion