Multipoint <i>Kras</i> oncogene mutations potentially indicate mucinous carcinoma on the entire spectrum of mucinous ovarian neoplasms

Abstract

// Yi-Ju Lee 1,2 , Ming-Yung Lee 3 , Alexandra Ruan 4 , Chi-Kuan Chen 5 , Hao-Ping Liu 6 , Chau-Jong Wang 7,8 , Wan-Ru Chao 9,* and Chih-Ping Han 9,10,* 1 Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan 2 Department of Pathology, Chung-Shan Medical University Hospital, Taichung, Taiwan 3 Department of Statistics and Informatics Science, Providence University, Taichung, Taiwan 4 Stanford School of Medicine, Stanford, California, USA 5 Department of Pathology; Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan and Department of Medicine, Mackay Medical College, Taiwan 6 Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan 7 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan 8 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 9 Department of Pathology, Chung-Shan Medical University and Chung Shan Medical University Hospital, Taichung, Taiwan 10 Department of Obstetrics and Gynecology, Chung-Shan Medical University and Chung-Shan Medical University Hospital, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Chih-Ping Han, email: // Wan-Ru Chao, email: // Keywords : mucinous adenoma (MA), mucinous borderline tumor (MBT), mucinous carcinoma (MC), anti-epidermal growth factor receptor (anti-EGFR), Pathology Section Received : September 20, 2016 Accepted : October 28, 2016 Published : November 18, 2016 Abstract Kras mutation is a common phenomenon in many human neoplasms. We aimed to assess the Kras mutational status along the histological continuum from normal ovaries to the development of benign, borderline and malignant ovarian mucinous neoplasms. We analyzed 41 cases of malignant, 10 cases of borderline, 7 cases of benign mucinous ovarian tumors and 7 cases of normal ovarian tissue. The prevalence of Kras mutations in the normal ovary was 0.00% ( n =0/7), while the prevalence in benign, borderline and malignant mucinous neoplasms was 57.14% ( n =4/7), 90.00% ( n =9/10) and 75.61% ( n =31/41), respectively. Multiple Kras mutations were detected in 6 cases of mucinous carcinoma, including 5 double mutations with G13D/V14I ( n =1), G12V/G13S ( n =1), G12D/G13S ( n =3) and one triple mutation with A11V/G13N/V14I ( n =1). We identified six cases with 3 novel Kras mutations not previously described in the COSMIC database, which included A11V ( n =3) and V14I ( n =2) in mucinous carcinomas, and A11T ( n =1) in a mucinous borderline tumor. In conclusion, Kras mutation appears to be one of the imperative events in the ovarian mucinous adenoma &ndash; borderline tumor &ndash; carcinoma sequence, as increased numbers of Kras mutations have been shown to be the strongest predictor of unequivocal malignancy in ovarian mucinous neoplasms.