Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma

Agnes Stephanie Harahap
,
Imam Subekti
,
Sonar Soni Panigoro
ORCID logo ,
Asmarinah Asmarinah
,
Lisnawati Lisnawati
,
Retno Asti Werdhani
,
Hasrayati Agustina
,
Dina Khoirunnisa
ORCID logo ,
Mutiah Mutmainnah
ORCID logo ,
Fajar Lamhot Gultom
,
Abdillah Hasbi Assadyk
,
Maria Francisca Ham
*
Version 1 : Received: 13 September 2023 / Approved: 14 September 2023 / Online: 15 September 2023 (10:54:29 CEST)

A peer-reviewed article of this Preprint also exists.

Harahap, A.S.; Subekti, I.; Panigoro, S.S.; Asmarinah; Lisnawati; Werdhani, R.A.; Agustina, H.; Khoirunnisa, D.; Mutmainnah, M.; Gultom, F.L.; Assadyk, A.H.; Ham, M.F. Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression. Biomedicines 2023, 11, 2803. Harahap, A.S.; Subekti, I.; Panigoro, S.S.; Asmarinah; Lisnawati; Werdhani, R.A.; Agustina, H.; Khoirunnisa, D.; Mutmainnah, M.; Gultom, F.L.; Assadyk, A.H.; Ham, M.F. Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression. Biomedicines 2023, 11, 2803.

Abstract

The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive models for BRAFV600E and RAS-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the BRAF and RAS genes. Multivariate logistic regression was employed to develop prediction model. Independent predictors for the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology variant, and pERK1/2 levels exceeding 10% (X2=0.128, P>0.05, AUC=0.734, P<0.001). RAS mutation predictive model includes follicular histology variant and pERK1/2 expression >10% (X2=0.174, P>0.05, AUC=0.8, P<0.001). We proposed using the prediction model concurrently with four potential combination group outcomes. PTC cases included in combination of low BRAFV600E-scoring group and high RAS-scoring group are categorized as RAS-like (adjOR=4.857, P=0.01, 95% CI=1.470-16.049). PTCs included in combination of high BRAFV600E-scoring group and low RAS-scoring group are categorized as BRAF-like PTCs (adjOR=3.091, P=0.001, 95% CI=1.594-5.995). The different prediction models indicate variations in biological behaviour between BRAF-like and RAS-like PTCs, necessitating adjustments in treatment approaches.

Keywords

papillary thyroid carcinoma; BRAF-like; RAS-like; BRAFV600E; RAS mutation; prediction model

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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