BRAF MUTATION IN COLORECTAL CARCINOMA IS ASSOCIATED WITH TUMOR DEPTH, LOCATION, GRADE AND PD-L1 EXPRESSION: SINGLE CENTER EXPERIENCE

Authors

  • Blagica Krsteska Institute of Pathology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia Faculty of Medical Sciences, Goce Delchev University, Shtip, Republic of North Macedonia
  • Vanja Filipovski Department of Histopathology and Cytology, Clinical Hospital Acibadem - Sistina, Skopje, Republic of North Macedonia Faculty of Medical Sciences, Goce Delchev University, Shtip, Republic of North Macedonia
  • Katerina Kubelka-Sabit Department of Histopathology and Cytology, Clinical Hospital Acibadem - Sistina, Skopje, Republic of North Macedonia Faculty of Medical Sciences, Goce Delchev University, Shtip, Republic of North Macedonia
  • Dzengis Jasar Department of histopathology and cytology, Clinical Hospital Acibadem-Sistina, Skopje, North Macedonia Faculty of Medical Sciences, Goce Delchev University, Shtip, Republic of North Macedonia
  • Magdalena Bogdanovska-Todorovska Institute of Pathology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Nevenka Velickova Faculty of Medical Sciences, Goce Delchev University, Shtip, Republic of North Macedonia

Keywords:

colorectal cancer, BRAF mutation, PDL-1

Abstract

Introduction: BRAF mutations in colorectal carcinoma (CRC) are a known marker of poor prognosis and aggressive tumor behavior.

Aim: This study aimed to evaluate the correlation of BRAF mutations with tumor depth, anatomical location, histological grade, and programmed death-ligand 1 (PD-L1) expression in colorectal carcinoma.

Material and methods: A retrospective prospective analysis was conducted on 152 cases of CRC diagnosed at the Clinical Hospital Acibadem - Sistina. Tumor samples were tested for BRAF mutations and immunohistochemically stained for PD-L1 expression (clone SP263). Tumor depth and location were documented, and histological grades were determined. PD-L1 expression was assessed at cut-offs of 1-10%, 10-50%, and 50-100% of positive tumor cells.

Results: BRAF mutations were identified in 7.24% of cases, predominantly in right-sided colon tumors. Mutated cases exhibited greater tumor depth and higher histological grade (G3) compared to BRAF wild-type tumors. PD-L1 expression (50-100%) was significantly associated with BRAF-mutated tumors, particularly in advanced stages (IIIC and IVA). These tumors showed a higher likelihood of being located in the right colon and were linked to poorer differentiation and increased immune checkpoint expression.

Conclusion: BRAF mutations in CRC are associated with aggressive tumor characteristics, including greater depth, high grade, and right-sided location. The strong correlation with PD-L1 expression suggests potential therapeutic benefits of immune checkpoint inhibitors in BRAF-mutated CRC cases. Early identification of these mutations is crucial for optimizing patient outcomes.

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Published

2025-04-11

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Original Articles