Clinicopathological Characteristics and Mutation Spectrum of Colorectal Adenocarcinoma With Mucinous Component in a Chinese Cohort: Comparison With Classical Adenocarcinoma

Abstract

Background: Colorectal adenocarcinoma with mucinous component (AWMC) is a special entity of colorectal cancer. The study is aimed at analyzing the clinicopathological characteristics, mutation spectrum, and prognosis of AWMC and comparing it with classical adenocarcinoma (AC) in a Chinese cohort.Methods: One hundred eight AMWC and 204 AC patients were included. Targeted next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded (FFPE) tissues. AWMC was further divided into two groups: AWMC with signet ring cell component and AWMC without signet ring cell component. Clinicopathological features, mismatch repair protein (MMR) status, genetic alterations, and survival outcomes were analyzed after tumor location was taken into consideration.Results: AWMC had larger tumor size (p = 0.014) and showed predilection for proximal colon (p < 0.001) compared with AC. Regardless of primary sites, AWMC was associated with less metastasis (p < 0.001) and earlier AJCC stage (p < 0.001). Mismatch repair protein deficiency (dMMR) was more commonly detected in AWMC than in AC for right-sided colon (p < 0.001), but the difference was not significant for left-sided colon (p = 0.081). The five most commonly mutated genes in AWMC were KRAS (45.4%), TP53 (39.8%), APC (22.2%), PIK3CA (22.2%), and SMAD4 (10.2%). AWMC showed a significantly lower mutation rate of TP53 than AC, both in right-sided colon and in left-sided colon (p < 0.001 and p = 0.033, respectively). In left-sided colon, AWMC with signet ring cell component had a significantly smaller size than tumors with signet ring cell component (p = 0.034). No dMMR cases were detected in AWMC with signet ring cell component (n = 7). Moreover, AWMC with signet ring cell component had a significantly lower KRAS mutation rate than AWMC without signet ring cell component, both in right-sided colon and in left-sided colon (p = 0.036 and p = 0.012, respectively). The disease-specific survival (DSS) for AWMC and AC were not statistically different Chen et al.Colorectal Adenocarcinoma With Mucinous Component (p = 0.0587). Multivariate analysis showed that AWMC was not an independent predictor of prognosis. Conclusion:Regardless of primary sites, AWMC demonstrates less metastasis, earlier stages, more frequent dMMR, and lower TP53 mutation rate than AC. Our results indicate that different molecular pathogenesis might underlie mucinous morphology in colorectal carcinoma. Mucinous component is not an independent factor of outcome.

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

“…Most currently studies comparing CRC with MAC use this criterion, nevertheless, their impact on patients' prognosis has remained controversial. The present results do not agree with some previous reports [3,10] but support those of a recent study by Gonzalez et al [5] and Chen et al [2], in which they state that the proportion of mucinous component of MAC has no signi cant in uence on patient prognosis. While mucinous features should still be mentioned, utilizing criteria such as a 50% cut off is not supported by our data.…”

“…Despite several studies comparing underlying clinicopathological differences between MAC and conventional CRC. Still, controversial results relating prognostic value of mucinous histology have been reported [2][3][4][5][6][7]. Till present, the prognostic value of MAC remains undetermined when the locations of the tumor, molecular alterations, population characteristics or different treatment plans are taken into account.…”

Clinicopathological and Molecular Features of Colorectal Cancer Patients With Mucinous and Non-Mucinous Adenocarcinoma

“…MAC is more frequently found in the proximal colon and less common in Asian countries. Whether MAC is associated with prognosis in CRC patients is controversial ( 5 – 8 ). Right-sided colon cancer tends to have a more advanced tumor stage and poor differentiation and be mucinous ( 9 ).…”

“…Regarding the clinicopathological and genetic features, MAC was more likely to be located in the proximal colon, to have a microsatellite instability (MSI) phenotype, to have altered expression of MLH1 , FHIT , and p27 and to have a lower rate of TP53 mutation than non-mucinous adenocarcinoma (NMAC) ( 4 , 5 ). The prognosis of MAC compared to NMAC in CRC is debated.…”

“…The prognosis of MAC compared to NMAC in CRC is debated. Some studies reported that MAC was associated with a worse survival than NMAC ( 6 , 7 ); however, MAC was reported to have a similar survival ( 5 ) and an even better prognosis ( 8 ) than NMAC.…”