Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression

Autor: Agnes Stephanie Harahap, Imam Subekti, Sonar Soni Panigoro, Asmarinah, Lisnawati, Retno Asti Werdhani, Hasrayati Agustina, Dina Khoirunnisa, Mutiah Mutmainnah, Fajar Lamhot Gultom, Abdillah Hasbi Assadyk, Maria Francisca Ham
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Biomedicines, Vol 11, Iss 10, p 2803 (2023)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines11102803
Popis: 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 retrospective 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 models. Independent predictors of the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology subtype, and pERK1/2 levels exceeding 10% (X2 = 0.128, p > 0.05, AUC = 0.734, p < 0.001). The RAS mutation predictive model includes follicular histology subtype and pERK1/2 expression > 10% (X2 = 0.174, p > 0.05, AUC = 0.8, p < 0.001). We propose using the prediction model concurrently with four potential combination group outcomes. PTC cases included in a combination of the 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 a combination of the 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 behavior between BRAF-like and RAS-like PTCs.
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