Mucinous adenocarcinoma: A unique clinicopathological subtype in colorectal cancer

Abstract

Mucinous adenocarcinoma (MAC) is a unique clinicopathological subtype of colorectal cancer, which is characterized by extracellular mucinous components that comprise at least 50% of the tumor tissue. The clinical characteristics, molecular features, response to chemo-/radiotherapy, and prognosis of MAC are different from that of non-MAC (NMAC). MAC is more common in the proximal colon, with larger volume, higher T-stage, a higher proportion of positive lymph nodes, poorer tumor differentiation, and a higher proportion of peritoneal implants compared to NMAC. Although biopsy is the main diagnostic method for MAC, magnetic resonance imaging is superior in accuracy, especially for rectal carcinoma. The aberrant expression of mucins, including MUC1, MUC2 and MUC5AC, is a notable feature of MAC, which may be related to tumor invasion, metastasis, inhibition of apoptosis, and chemo-/radiotherapy resistance. The genetic origin of MAC is mainly related to BRAF mutation, microsatellite instability, and the CpG island methylator phenotype pathway. In addition, the poor prognosis of rectal MAC has been confirmed by various studies, and that of colonic MAC is still controversial. In this review, we summarize the epidemiology, clinicopathological characteristics, molecular features, methods of diagnosis, and treatments of MAC in order to provide references for further fundamental and clinical research.

Patients with Metachronous Peritoneal Metastatic Mucinous Colorectal Adenocarcinoma Benefit More from Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) than Their Synchronous Counterparts

“…Adenocarcinoma is the most common histological subtype of CRC, approximately 10–20% of which can be characterized as MAC [ 22 ], but some geographical differences can be observed in the prevalence of the disease: Western countries are more frequently affected [ 23 , 24 ]. By definition, MAC is described as a unique subtype of AC in which more than 50% of the tumor tissue is comprised of extracellular mucinous components [ 12 , 22 , 24 ].…”

“…Adenocarcinoma is the most common histological subtype of CRC, approximately 10–20% of which can be characterized as MAC [ 22 ], but some geographical differences can be observed in the prevalence of the disease: Western countries are more frequently affected [ 23 , 24 ]. By definition, MAC is described as a unique subtype of AC in which more than 50% of the tumor tissue is comprised of extracellular mucinous components [ 12 , 22 , 24 ]. It has been previously reported that MAC tends to develop more often in younger patients [ 25 ]; furthermore, a higher T-stage and N-stage at the time of diagnosis and the dominance of a right-sided location of the tumor are more characteristic of MAC [ 12 , 22 ].…”

“…Based on the limited number of RAS results we could obtain (RAS mutant rate: AC 45%, MAC 75%), we would most likely have presented the same data as above. In addition, the gene expression profiling of MAC revealed numerous differentially expressed genes involved in cellular differentiation and mucin metabolism (MUC1, MUC2, and MUC5AC) [ 22 , 24 , 25 , 26 , 32 ].…”

“…The neo/adjuvant treatment of MAC neoplasms is challenging: an impaired response to treatment and a shorter survival of patients is reported in most of the studies [ 22 , 24 , 33 ]. Some reports have suggested that the response to treatment in lower-stage MAC patients does not differ from that of non-MAC patients [ 34 , 35 ], but basically all of the studies agree that, in advanced stages, the therapy response of MAC is lower regardless the chemotherapy combination used [ 22 , 24 , 33 ]. Several novel therapeutic options have also emerged lately, including immunotherapies [ 22 , 24 ], drugs targeting mucins [ 36 ], and the possible use of nanoparticle drugs [ 22 ].…”

“…Some reports have suggested that the response to treatment in lower-stage MAC patients does not differ from that of non-MAC patients [ 34 , 35 ], but basically all of the studies agree that, in advanced stages, the therapy response of MAC is lower regardless the chemotherapy combination used [ 22 , 24 , 33 ]. Several novel therapeutic options have also emerged lately, including immunotherapies [ 22 , 24 ], drugs targeting mucins [ 36 ], and the possible use of nanoparticle drugs [ 22 ]. Clinical studies have investigated the effect of immune checkpoint markers in CRC patients with tumors displaying high microsatellite instability and mismatch repair deficiency [ 37 , 38 , 39 , 40 , 41 , 42 ].…”