Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence.

Autor:	Foda AAM; Department of Anatomic Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.; Department of Pathology, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia., El-Hawary AK; Department of Anatomic Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.; Pathology Department, Horus Faculty of Medicine, Horus University, New Damietta, Egypt., Elnaghi K; Medical Oncology Unit, Internal Medicine Faculty of Medicine, Oncology Centre, Mansoura, Egypt.; Medical Oncology Department, Oncology Center King Abdullah Medical City, Makkah, Saudi Arabia., Eldehna WM; Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt.; Department of Oncology, International Medical Center, Jeddah, Saudi Arabia., Enan ET; Department of Anatomic Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Jazyk:	angličtina
Zdroj:	Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine [Tumour Biol] 2024; Vol. 46 (1), pp. 1-11.
DOI:	10.3233/TUB-230038
Abstrakt:	Background: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. Objective: The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. Methods: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. Results: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). Conclusions: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.
Databáze:	MEDLINE
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