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

Banias,Laura; Jung,Ioan; Bara,Tivadar; Fulop,Zsolt; Simu,Patricia; Simu,Iunius; Satala,Catalin; Gurzu,Simona

doi:10.3892/ol.2019.11228

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

Authors:
- Laura Banias
- Ioan Jung
- Tivadar Bara
- Zsolt Fulop
- Patricia Simu
- Iunius Simu
- Catalin Satala
- Simona Gurzu
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Affiliations: Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, ‘George Emil Palade’, 540139 Targu‑Mures, Romania, Department of Surgery, University of Medicine, Pharmacy, Sciences and Technology, ‘George Emil Palade’, 540139 Targu‑Mures, Romania, Department of Radiology, University of Medicine, Pharmacy, Sciences and Technology, ‘George Emil Palade’, 540139 Targu‑Mures, Romania
Published online on: December 18, 2019 https://doi.org/10.3892/ol.2019.11228
Pages: 1487-1495
Copyright: © Banias et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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