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

Abstract

Background: Mucinous 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. Methods: The 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. Results: We 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. Conclusions: The 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.

Clinicopathological characteristics, molecular alterations and prognosis of mucinous histology in colorectal adenocarcinoma patients

“…Like in other studies, these two gene (KRAS and BRAF) mutations were mutually exclusive [17,18]. Similar to Xiaodong Li's study [16], we found that both BRAF or KRAS mutations has no correlation with amount of mucinous component in the tumours.…”

“…Among these,the KRAS mutation rate was equal to 38.5%, which was close to most of the previous reports either about Chinese or other ethnicities in CRC patients [2,14.15]. BRAF mutation rates are signi cantly different in previous studies of Chinese population [16]. Like in other studies, these two gene (KRAS and BRAF) mutations were mutually exclusive [17,18].…”

Clinical, Morphologic, and Molecular Features Associated With Ovarian Metastases From Pattern A Endocervical Adenocarcinomas

“…Somatic KRAS mutations are known to occur in a number of different tumor types, particularly mucinous adenocarcinomas, including HPV-associated and HPV-independent EAs. [30][31][32][33][34] Somatic mutations, including those in KRAS, have also been correlated with the pattern-based classification system. 35,36 In a prior study by one of our group (A.H.), none of the 5 pattern A EAs harbored KRAS mutations.…”

The importance of precision medicine in modern molecular oncology

“…However, recently a study based on NGS reveals that abnormal EGFR pathway is involved in the CRC independent of the percentage of mucinous components. 78 With the precision medicine initiative launched, we believe that more genetic and epigenetic factors/biomarkers will be explored. As molecular prognostic biomarkers are the basic components of precision medicine, and accurate diagnosis is the premise of accurate treatment.…”

“…For example, the mucinous adenocarcinoma is defined through the index of 50% mucin component declined. However, recently a study based on NGS reveals that abnormal EGFR pathway is involved in the CRC independent of the percentage of mucinous components 78 …”