Diagnostic and Prognostic Value of Isolated and Combined MCM3 and Glypican-3 Expression in Hepatocellular Carcinoma: A Novel Immunosubtyping Prognostic Model.

Despite diagnostic and therapeutic advances, hepatocellular carcinoma (HCC) remains a leading cause of morbidity/mortality worldwide. This retrospective study investigates the isolated and combined mini-chromosome maintenance complex component 3 (MCM3) and glypican-3 (GPC3) immunohistochemical (IHC) expression in HCC. A novel HCC immunosubtyping model based on combined MCM3/GPC3 expression is introduced and tested in comparison with prognostic variables and survival outcomes. Seventy-six HCC patients who underwent hepatectomy were enrolled. After the collection of clinicopathological, laboratory, and 3-year-survival data, IHC was applied to HCC tissue microarray-prepared sections using anti-MCM3 and GPC3. IHC scoring divided HCCs as: MCM3-high and MCM3-low expression, GPC3-positive and GPC3-negative expression, and combined scoring model immunosubtypes: MCM3-high/GPC3-positive; MCM3-low/GPC3-positive; MCM3-high/GPC3-negative, and MCM3-low/GPC3-negative. Statistical and Kaplan-Meier survival analyses were performed using SPSS version 23. MCM3 was expressed in 84.2% of HCCs. MCM3-high HCCs (60.5%) were significantly associated with lack of tumor capsulation, portal vein thrombosis, high grades, advanced stages, and Child-Pugh Scores B and C (all P≤0.05), and had a tendency for multiplicity, metastasis, solid growth pattern, shorter overall survival (OS) and disease-free survival (DFS). GPC3-positve HCCs (56.6%) were significantly associated with multiplicity and higher alfa-fetoprotein (all P≤0.05) with a tendency for shorter OS and DFS. Among all isolated and combined-expression immunosubtypes, MCM3-high/GPC3-positive HCCs had the worst prognosis and the shortest OS and DFS whereas MCM3-low/GPC3-negative immunosubtype showed the best prognosis and had the longest OS and DFS. MCM3 is defined as diagnostic, prognostic marker, and potential therapeutic target in HCC. The novel MCM3/GPC3 immunosubtyping model provides prognostic indications and stratification criteria for patients with HCC. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Abdelaty Shawky Mohamed, Amal Abd El Hafez, Ahmed Eltantawy, Mena Mahfouz. Diagnostic and Prognostic Value of Isolated and Combined MCM3 and Glypican-3 Expression in Hepatocellular Carcinoma: A Novel Immunosubtyping Prognostic Model. Applied immunohistochemistry & molecular morphology : AIMM. 2022 Nov-Dec 01;30(10):694-702

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PMID: 36350065

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