Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer

Abstract

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p < 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (p < 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (p < 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness.

Mucin phenotypes and clinicopathological features of colorectal adenocarcinomas: Correlation with colorectal adenocarcinoma with enteroblastic differentiation

“…MUC5AC expression has been reported in association with expression in microsatellite-unstable/mismatch repair-deficient tumors [21]. Rico et al study showed a strong association of MUC5AC expression with mismatch repair deficiency (dMMR) in colorectal cancers [31]. Kesari et al have reported that MUC5AC expression increased as the stage of disease progressed from 1 to 4 [17].…”

Mucin 5AC expression is common but unrelated to tumor progression in pancreatic adenocarcinoma

“…Of note, the few studies investigating the clinical relevance of MUC5AC expression in other cancer types have also led to discrepant findings. High MUC5AC expression was linked to favorable tumor parameters in gastric and ovarian cancer, 39 unrelated to tumor phenotype in breast and colorectal cancer, 19,[40][41] and linked to an unfavorable phenotype in lung cancers. 42 Based on these findings, it cannot be excluded, that the biological role of MUC5AC expression in cancer cells might be dependent on the tumor type.…”

“…Tissue microarray sections were stained and analyzed for MUC5AC as described previously by Rico et al 19 In brief, primary antibody specific against MUC5AC protein (mouse monoclonal, MSVA-109, MS Validated Antibodies, Hamburg, Germany) was applied at 1:200 dilution after antigen retrieval of the tissue sections at 121°C for 5 min in pH 7.8 TRIS-EDTA buffer. Mucin 5AC staining was seen in the membrane and cytoplasm of the cancer cells and immunostaining was interpreted as follows: Negative: no staining; weak: staining intensity of 1 + in ≤ 70% of the tumor cells or staining intensity of 2 + in ≤ 30% of the tumor cells; moderate: 1 + in > 70%, or 2 + in > 30% but in ≤ 70%, or 3 + in ≤ 30% of the tumor cells; strong: 2 + in > 70% or 3 + in > 30% of the tumor cells.…”

Ulcerative Colitis: Novel Epithelial Insights Provided by Single Cell RNA Sequencing

“…However, MUC5AC was not reported among the core mucus proteins in active UC ( 45 ). MUC5AC is frequently present in colorectal adenomas and colon cancers, thus it’s elevation might be due to UC-induced carcinogenesis ( 48 ).…”