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

Abstract

Background Mucinous adenocarcinoma (MAC) is conventionally diagnosed by WHO definition when the extracellular mucin is more than 50% of the tumour area. The study is aimed at analyzing the clinicopathological characteristics, mutation spectrum, and prognosis of the colorectal adenocarcinoma (CRC) with any mucinous proportion or feature. Methods Clinical and pathological information for 50 patients were reviewed and recorded. Mutation analyses for exon 2–4 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing. Expression of DNA mismatch repairs (MMRs) and P53 proteins was evaluated by immunohistochemistry (IHC). Density of tumour infiltrating lymphocyte (TIL) status was scored. We also evaluated the percentage of glands producing mucin and the morphology of the different tumor cells types in mucin pools. We retrospectively analyzed prognosis of 43 patients with Stage II-III MAC. The primary outcome was progression-free survival (PFS). Results The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%, respectively. Patients with MAC exhibiting high levels of mucin were related to the increase of tumor diameter (P = 0.038), but were not associated with any of the other clinicopathological parameters. The proportion or variable morphology of mucinous component did not stratify PFS in Stage II-III tumours. It is interesting to note that male patients had lower TIL compared with female patients (P = 0.018). TIL-low tumors were also correlated with advanced stage (P = 0.041). TIL status was a strong independent predictor of PFS in stage II-III mucinous component tumours (p < 0.001). All four IV stage patients were also classified into TIL-low case. No parameters were independently associated with outcome after adjusting for tumour stage in multivariate analysis. Conclusions TIL status could more accurately determine the biology of the MAC feature for appropriate management, irrespective of quantity or morphology of mucinous component.

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy

“…In stiff breast cancer tissue, YAP also induces macrophage M2 polarization and subsequently inhibits CD8 + T-cell activity and promotes tumor progression [82]. Furthermore, macrophage M2 polarization was increased in colorectal cancer by activating the Rho/Hippo/YAP signaling pathway [83]. Taken together, matrix stiffness can shape macrophage polarization and function through YAP/TAZ mechanotransduction molecules in the cancer microenvironment.…”