Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study

Background: Ameloblastoma is the most frequently encountered, enigmatic odontogenic tumor whose etiopathogenesis is still controversial. Understanding the pathogenic mechanism involved in Ameloblastoma and its proliferation aids in determining the best treatment option at an early stage. MAPK pathwa...

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Main Authors: Aishwariya Mohanty, Abikshyeet Panda, Pallavi Mishra, Lipsa Bhuyan, Harish Kumar
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:Oral Oncology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772906024002887
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author Aishwariya Mohanty
Abikshyeet Panda
Pallavi Mishra
Lipsa Bhuyan
Harish Kumar
author_facet Aishwariya Mohanty
Abikshyeet Panda
Pallavi Mishra
Lipsa Bhuyan
Harish Kumar
author_sort Aishwariya Mohanty
collection DOAJ
description Background: Ameloblastoma is the most frequently encountered, enigmatic odontogenic tumor whose etiopathogenesis is still controversial. Understanding the pathogenic mechanism involved in Ameloblastoma and its proliferation aids in determining the best treatment option at an early stage. MAPK pathway are known to be active during tooth development, and also mutations in MAPK components have been identified in both benign and malignant tumors. The aim of this study was to evaluate the Immunohistochemical expression of biomarker BRAF V600E and K-RAS in Ameloblastoma and to examine if any, correlation exists between BRAF V600E and K-RAS expression. Methods: 30 formalin-fixed paraffin-embedded blocks of histopathologically diagnosed cases of Ameloblastoma were taken as samples. Immunohistochemistry using K-RAS and BRAF V600E antibody was performed and slides were evaluated both quantitatively and qualitatively using a quick score by an independent observer. Results: K-RAS and BRAF V600E immunoexpression was evaluated and there is a significantly higher expression of K-RAS (mean score 6.20 ± 1.883) when compared with BRAF V600E (mean score 4.50 ± 2.271). BRAF V600E and K-RAS act independently in the pathogenesis of Ameloblastoma as the pattern of variation of BRAF V600E score was uneven when compared to K-RAS values. Conclusion: Our data provide evidence that two independent mutation occurs in the same molecular pathway driving Ameloblastomas. But there is no correlation between K-RAS and BRAF V600E expression. Hence, combination therapy of K-RAS and BRAF V600E inhibitors can be helpful for the treatment of Ameloblastoma.
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spelling doaj-art-6d753d5b4ffc4dfb9fa128ead3c706a22025-01-09T06:16:17ZengElsevierOral Oncology Reports2772-90602024-06-0110100442Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical studyAishwariya Mohanty0Abikshyeet Panda1Pallavi Mishra2Lipsa Bhuyan3Harish Kumar4Department of Oral & Maxillofacial Pathology and Oral Microbiology, S.C.B Dental College and Hospital, Cuttack, Odisha, IndiaDepartment of Oral & Maxillofacial Pathology and Oral Microbiology, Kalinga Institute of Dental Sciences, KIIT Deemed to Be University, Bhubaneswar, India; Corresponding author.Department of Oral & Maxillofacial Pathology and Oral Microbiology, Kalinga Institute of Dental Sciences, KIIT Deemed to Be University, Bhubaneswar, IndiaDepartment of Oral & Maxillofacial Pathology and Oral Microbiology, Kalinga Institute of Dental Sciences, KIIT Deemed to Be University, Bhubaneswar, IndiaDepartment of Oral & Maxillofacial Pathology and Oral Microbiology, Kalinga Institute of Dental Sciences, KIIT Deemed to Be University, Bhubaneswar, IndiaBackground: Ameloblastoma is the most frequently encountered, enigmatic odontogenic tumor whose etiopathogenesis is still controversial. Understanding the pathogenic mechanism involved in Ameloblastoma and its proliferation aids in determining the best treatment option at an early stage. MAPK pathway are known to be active during tooth development, and also mutations in MAPK components have been identified in both benign and malignant tumors. The aim of this study was to evaluate the Immunohistochemical expression of biomarker BRAF V600E and K-RAS in Ameloblastoma and to examine if any, correlation exists between BRAF V600E and K-RAS expression. Methods: 30 formalin-fixed paraffin-embedded blocks of histopathologically diagnosed cases of Ameloblastoma were taken as samples. Immunohistochemistry using K-RAS and BRAF V600E antibody was performed and slides were evaluated both quantitatively and qualitatively using a quick score by an independent observer. Results: K-RAS and BRAF V600E immunoexpression was evaluated and there is a significantly higher expression of K-RAS (mean score 6.20 ± 1.883) when compared with BRAF V600E (mean score 4.50 ± 2.271). BRAF V600E and K-RAS act independently in the pathogenesis of Ameloblastoma as the pattern of variation of BRAF V600E score was uneven when compared to K-RAS values. Conclusion: Our data provide evidence that two independent mutation occurs in the same molecular pathway driving Ameloblastomas. But there is no correlation between K-RAS and BRAF V600E expression. Hence, combination therapy of K-RAS and BRAF V600E inhibitors can be helpful for the treatment of Ameloblastoma.http://www.sciencedirect.com/science/article/pii/S2772906024002887AmeloblastomaK-RASBRAF V600EPathogenesisMAPK pathwayOdontogenic tumors
spellingShingle Aishwariya Mohanty
Abikshyeet Panda
Pallavi Mishra
Lipsa Bhuyan
Harish Kumar
Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study
Oral Oncology Reports
Ameloblastoma
K-RAS
BRAF V600E
Pathogenesis
MAPK pathway
Odontogenic tumors
title Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study
title_full Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study
title_fullStr Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study
title_full_unstemmed Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study
title_short Frequent mutation of K-RAS in addition to BRAF V600E in Ameloblastoma – An immunohistochemical study
title_sort frequent mutation of k ras in addition to braf v600e in ameloblastoma an immunohistochemical study
topic Ameloblastoma
K-RAS
BRAF V600E
Pathogenesis
MAPK pathway
Odontogenic tumors
url http://www.sciencedirect.com/science/article/pii/S2772906024002887
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