Immunohistochemical‑based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial‑mesenchymal transition

Abstract

The aim of the present study was to classify colorectal carcinoma (CRC) into molecular subtypes, based on immunohistochemical (IHC) assessments. A total of 112 CRC samples were molecularly classified based on the expression levels of epithelial-mesenchymal transition (EMT)-associated IHC markers. A total of three molecular subtypes were defined: Epithelial, membrane positivity for E-cadherin and β-catenin, negative for vimentin; mesenchymal, E-cadherin-negative, nuclear β-catenin-and vimentin-positive; and hybrid cases, epithelial tumor core and mesenchymal tumor buds. Most of the cases were diagnosed as moderately differentiated adenocarcinoma (n=89; 79.46%). The majority of cases (n=100; 89.28%) exhibited a mismatch repair proficient status (microsatellite stable CRCs). A predominance of epithelial-type (n=51; 45.54%) and hybrid CRCs (n=47; 41.96%) was observed, whereas a few cases (n=14; 12.50%) were classified as mesenchymal-type CRCs. This molecular classification was associated with pathological stage (P<0.01), pT stage (P=0.04), pN stage (P<0.01), the grade of tumor budding (P=0.04), and maspin expression in both the tumor core (P=0.04) and the invasion front (P<0.01). The mesenchymal-type cases predominantly exhibited lymph node metastases, high-grade budding and a tendency towards maspin nuclear predominance. All epithelial-type cases with maspin-only expression (n=18) were non-metastatic. Patients with CRC of the epithelial subtype and those with a lymph node ratio (LNR) ≤0.15 presented the best overall survival, followed by those with hybrid and mesenchymal subtypes. Nuclear maspin positivity was more frequent in cases with a high-budding degree compared with those with a low-budding degree (P=0.03). The EMT-associated molecular classification of CRCs may be used to identify the most aggressive CRCs, which show a mesenchymal phenotype, high-budding degree, maspin nuclear positivity and lymph node metastases. The pN stage, LNR and budding degree of patients, which can be evaluated with maspin expression, remain the most important prognostic factors.

Molecular profiling of the colon cancer in South-Eastern Romania

“…To our knowledge, the current study is one of the few in our country which assessed the MSI status of the CRC by PCR method (additionally to IHC method) and investigated the BRAF mutations in all patients. [ 48 ] Molecular analyses on CRC were also performed in our region, but they were based on the investigation of microRNAs. [ 49 ]…”

Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

“…Based on the rules used for colorectal carcinomas[ 5 , 7 ], which were adapted for GC[ 8 ], we also assessed the grade of dyscohesivity (tumor budding degree). In terms of the invasion front, we took into account at least 5 high power fields (HPF), and then classified the cases into five groups: 0–nodular growth intestinal type GCs (adenocarcinoma without buds); 1–adenocarcinoma with 1-4 dyscohesive cells in the invasion front (low grade); 2-adenocarcinoma with 5-9 dyscohesive cells in the invasion front (high grade); 3-adenocarcinoma with over 10 dyscohesive cells in the invasion front (high grade); and 4 – diffuse growth-GCs.…”

“…For p53, three groups were considered, based on the intensity and extent of stained tumor cell nuclei: Negative (< 5%), low (5%-50%) and high p53 expression (> 50%). For Maspin, we used a system of quantification, which was previously published by our team and is based on the subcellular localization of this protease, and cases were classified as negative, with cytoplasm positivity, nuclear predominance and mixed expression (dual positivity, in cytoplasm and nuclei)[ 3 , 4 , 5 , 10 ].…”

“…Maspin (Serpine B5) is a serine protease that is known to be involved in tumor cell proliferation and has antiangiogenic and anti-apoptotic properties against tumor cells[ 2 - 4 ]. Its regulatory functions depend on the subcellular localization (nucleus vs cytoplasm)[ 3 , 5 ]. In this study, we examined the p53 and Maspin immunohistochemical (IHC) expression, correlated with the mutation rate of TP53 gene, in GC samples.…”

Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

“…We chose to evaluate the epithelial to mesenchymal transition (EMT), which is known to induce aggressive tumor behavior and higher rates of chemoresistance [ 14 ]. The hybrid phenotype, which is characterized by loss of E-cadherin and membrane-to-nuclear translocation of β-catenin in tumor buds [ 15 ] was observed in two of the cases.…”