Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.