Colorectal carcinomas with mucinous differentiation are associated with high frequent mutation of KRAS or BRAF mutations, irrespective of quantity of mucinous component

Xiaodong Li,Haijuan Gao,Hongfa Zhu,Xiaoyan Liao,Katherine Sun,Ruliang Xu

doi:10.1186/s12885-020-06913-2

Abstract

BackgroundMucinous adenocarcinoma (MAC) is a distinct type of colorectal cancer (CRC) associated with poor response to treatment and poorer prognosis. MAC is diagnosed by WHO definition when the extracellular mucin is more than 50% of the lesion. We aimed at assessing the gene expression profiles of the CRCs with any mucinous features (> 5%) in a retrospective study.MethodsThe data of a 50-gene next generation sequencing (NGS) panel of 166 CRCs was analyzed and the gene mutational profile with morphologic features was correlated.ResultsWe identified the different genetic mutation profiles between CRCs with and without mucinous component, but noticed a similar genetic profile between MACs and CRCs with mucinous component, irrespective of the percentage (if mucinous component more than 5%). The different genetic mutation profile related to MSI status was also identified between two groups of tumors. The most frequent mutations in CRCs with mucinous component are KRAS (28/49, 57.1%) and BRAF (19/49, 38.7%), PIK3CA (16/49, 32.6%), followed by APC (12/49, 24.5%) and TP53 (11/49, 22.5%). The combined mutation frequency of the two key factors in the EGFR signaling pathway, KRAS and BRAF, in the CRCs with and without mucinous component is 95.9 and 52.1%, respectively.ConclusionsThe dysregulation of EGFR pathway plays a critical role in the development of CRCs with mucinous component, irrespective of the percentage. The result suggested that the current cut off of 50% mucin component to define mucinous adenocarcinoma might be challengeable.

Highlights

Mucinous adenocarcinoma (MAC) is a distinct type of colorectal cancer (CRC) associated with poor response to treatment and poorer prognosis
Very little studies have studied whether therapeutic efficacy of anti-epithelial growth factor receptor (EGFR) therapy can be attributed to mutation of Kirsten rat (KRAS) and BRAF associated with mucinous differentiation, and whether a different amount of the mucinous component could affect the genetic expression
In concordance with the results of study done by Gonsalves et al [6], our study has shown that KRAS and BRAF mutations are almost mutually exclusive and only one case had both mutations in this group

Summary

Introduction

Mucinous adenocarcinoma (MAC) is a distinct type of colorectal cancer (CRC) associated with poor response to treatment and poorer prognosis. Mucinous adenocarcinoma (MAC) is a unique histologic variant of CRC characterized by the extracellular deposition of mucin by the tumor cells This tumor usually occurs in the right colon, more in females, and has a poorer response to adjuvant chemotherapy and chemoradiotherapy [3,4,5]. V600E in 14% of colon cancers with nearly mutually exclusive genotype between each other [6] The mutation of these two genes is frequently seen in MACs [8–10], resulting in a poor response to anti-EGFR therapy [7, 11, 12]. Very little studies have studied whether therapeutic efficacy of anti-EGFR therapy can be attributed to mutation of KRAS and BRAF associated with mucinous differentiation (less than 50%), and whether a different amount of the mucinous component could affect the genetic expression

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