Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India
Introduction: Papillary thyroid carcinoma (PTC) has an excellent prognosis, but few cases are treatment-resistant. To check the applicability of combined BRAFV600E and MEK-targeted therapy, the current study correlated BRAFV600E with the MAPK pathway activation status in a cohort of PTCs. The progno...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2024-12-01
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| Series: | Indian Journal of Endocrinology and Metabolism |
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| Online Access: | https://journals.lww.com/10.4103/ijem.ijem_235_23 |
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| author | Nadeem Kocheri Priti Chatterjee Shipra Agarwal Mehar C. Sharma Sanjana Ballal Chandrasekhar Bal Sunil Chumber |
| author_facet | Nadeem Kocheri Priti Chatterjee Shipra Agarwal Mehar C. Sharma Sanjana Ballal Chandrasekhar Bal Sunil Chumber |
| author_sort | Nadeem Kocheri |
| collection | DOAJ |
| description | Introduction:
Papillary thyroid carcinoma (PTC) has an excellent prognosis, but few cases are treatment-resistant. To check the applicability of combined BRAFV600E and MEK-targeted therapy, the current study correlated BRAFV600E with the MAPK pathway activation status in a cohort of PTCs. The prognostic relevance of BRAFV600E and the usability of immunohistochemistry (IHC) for detecting the mutation were also assessed.
Methods:
Randomly selected 50 PTC and 15 non-PTC cases were re-classified according to the 2022 WHO classification. The BRAF mutation status was compared with the IHC of BRAFV600E, pERK1/2, pMEK1/2, and clinicopathological variables, including response to radioactive iodine and disease-free survival.
Results:
BRAFV600E mutation was present in 38%. Most (87.8%) cases were immunopositive for pMEK1/2 and 40% for pMEK1/2. Although BRAFV600E mutation did not correlate with the MAPK activation status, it had an adverse impact on tumour sensitivity to radioiodine (P < 0.05). Five of the seven radioiodine-resistant tumours were BRAFV600E-mutated. An Allred cut-off score of 7 had a sensitivity of 100% and a specificity of 84% for detecting the mutation by IHC. All the non-PTC cases were BRAF-wild type, but 20% showed weak immunopositivity for mutated protein and were scored 6.
Conclusions:
BRAFV600E-mutated PTCs are more likely to be RAI-resistant. MAPK pathway activation status did not vary significantly with BRAF mutation. Immunopositivity for pMEK1/2 in most suggests a scope for MEK1-targeted therapy in recalcitrant PTC cases even in the absence of the BRAF mutation. In addition, IHC is a reliable technique for detecting BRAFV600E mutation but needs validation by correlation with molecular studies. |
| format | Article |
| id | doaj-art-66ae8d797e83488380df78d5d9b5650f |
| institution | Kabale University |
| issn | 2230-8210 2230-9500 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Journal of Endocrinology and Metabolism |
| spelling | doaj-art-66ae8d797e83488380df78d5d9b5650f2025-01-09T12:23:39ZengWolters Kluwer Medknow PublicationsIndian Journal of Endocrinology and Metabolism2230-82102230-95002024-12-0128661762110.4103/ijem.ijem_235_23Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in IndiaNadeem KocheriPriti ChatterjeeShipra AgarwalMehar C. SharmaSanjana BallalChandrasekhar BalSunil ChumberIntroduction: Papillary thyroid carcinoma (PTC) has an excellent prognosis, but few cases are treatment-resistant. To check the applicability of combined BRAFV600E and MEK-targeted therapy, the current study correlated BRAFV600E with the MAPK pathway activation status in a cohort of PTCs. The prognostic relevance of BRAFV600E and the usability of immunohistochemistry (IHC) for detecting the mutation were also assessed. Methods: Randomly selected 50 PTC and 15 non-PTC cases were re-classified according to the 2022 WHO classification. The BRAF mutation status was compared with the IHC of BRAFV600E, pERK1/2, pMEK1/2, and clinicopathological variables, including response to radioactive iodine and disease-free survival. Results: BRAFV600E mutation was present in 38%. Most (87.8%) cases were immunopositive for pMEK1/2 and 40% for pMEK1/2. Although BRAFV600E mutation did not correlate with the MAPK activation status, it had an adverse impact on tumour sensitivity to radioiodine (P < 0.05). Five of the seven radioiodine-resistant tumours were BRAFV600E-mutated. An Allred cut-off score of 7 had a sensitivity of 100% and a specificity of 84% for detecting the mutation by IHC. All the non-PTC cases were BRAF-wild type, but 20% showed weak immunopositivity for mutated protein and were scored 6. Conclusions: BRAFV600E-mutated PTCs are more likely to be RAI-resistant. MAPK pathway activation status did not vary significantly with BRAF mutation. Immunopositivity for pMEK1/2 in most suggests a scope for MEK1-targeted therapy in recalcitrant PTC cases even in the absence of the BRAF mutation. In addition, IHC is a reliable technique for detecting BRAFV600E mutation but needs validation by correlation with molecular studies.https://journals.lww.com/10.4103/ijem.ijem_235_23brafv600eihcmapkpapillary thyroid carcinomaperkpmek |
| spellingShingle | Nadeem Kocheri Priti Chatterjee Shipra Agarwal Mehar C. Sharma Sanjana Ballal Chandrasekhar Bal Sunil Chumber Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India Indian Journal of Endocrinology and Metabolism brafv600e ihc mapk papillary thyroid carcinoma perk pmek |
| title | Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India |
| title_full | Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India |
| title_fullStr | Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India |
| title_full_unstemmed | Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India |
| title_short | Elucidating the Prognostic Role of BRAFV600E and the Activation Status of the Downstream MAPK Pathway in PTC: A Study from a Tertiary Centre in India |
| title_sort | elucidating the prognostic role of brafv600e and the activation status of the downstream mapk pathway in ptc a study from a tertiary centre in india |
| topic | brafv600e ihc mapk papillary thyroid carcinoma perk pmek |
| url | https://journals.lww.com/10.4103/ijem.ijem_235_23 |
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