Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression
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...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2803 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Agnes Stephanie Harahap |
| collection | DOAJ |
| description | 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 <i>BRAF</i>V600E and <i>RAS</i>-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the <i>BRAF</i> and <i>RAS</i> genes. Multivariate logistic regression was employed to develop prediction models. Independent predictors of the <i>BRAF</i>V600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology subtype, and pERK1/2 levels exceeding 10% (X<sup>2</sup> = 0.128, <i>p</i> > 0.05, AUC = 0.734, <i>p</i> < 0.001). The <i>RAS</i> mutation predictive model includes follicular histology subtype and pERK1/2 expression > 10% (X<sup>2</sup> = 0.174, <i>p</i> > 0.05, AUC = 0.8, <i>p</i> < 0.001). We propose using the prediction model concurrently with four potential combination group outcomes. PTC cases included in a combination of the low-<i>BRAF</i>V600E-scoring group and high-<i>RAS</i>-scoring group are categorized as RAS-like (adjOR = 4.857, <i>p</i> = 0.01, 95% CI = 1.470–16.049). PTCs included in a combination of the high-<i>BRAF</i>V600E-scoring group and low-<i>RAS</i>-scoring group are categorized as BRAF-like PTCs (adjOR = 3.091, <i>p</i> = 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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| last_indexed | 2024-03-10T21:24:17Z |
| publishDate | 2023-10-01 |
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| spelling | doaj.art-414b3c6e163a420d91a20aeaa7c0e6e02023-11-19T15:47:20ZengMDPI AGBiomedicines2227-90592023-10-011110280310.3390/biomedicines11102803Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry ExpressionAgnes Stephanie Harahap0Imam Subekti1Sonar Soni Panigoro2Asmarinah3Lisnawati4Retno Asti Werdhani5Hasrayati Agustina6Dina Khoirunnisa7Mutiah Mutmainnah8Fajar Lamhot Gultom9Abdillah Hasbi Assadyk10Maria Francisca Ham11Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Surgery, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Medical Biology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10310, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin General Hospital, Bandung 40161, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaDepartment of Anatomical Pathology, MRCCC Siloam Hospital, Jakarta 12930, IndonesiaDepartment of Otorhinolaryngology, Head and Neck Surgery, Harapan Kita National Women and Children Health Center, Jakarta 11420, IndonesiaDepartment of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, IndonesiaThe 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 <i>BRAF</i>V600E and <i>RAS</i>-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the <i>BRAF</i> and <i>RAS</i> genes. Multivariate logistic regression was employed to develop prediction models. Independent predictors of the <i>BRAF</i>V600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology subtype, and pERK1/2 levels exceeding 10% (X<sup>2</sup> = 0.128, <i>p</i> > 0.05, AUC = 0.734, <i>p</i> < 0.001). The <i>RAS</i> mutation predictive model includes follicular histology subtype and pERK1/2 expression > 10% (X<sup>2</sup> = 0.174, <i>p</i> > 0.05, AUC = 0.8, <i>p</i> < 0.001). We propose using the prediction model concurrently with four potential combination group outcomes. PTC cases included in a combination of the low-<i>BRAF</i>V600E-scoring group and high-<i>RAS</i>-scoring group are categorized as RAS-like (adjOR = 4.857, <i>p</i> = 0.01, 95% CI = 1.470–16.049). PTCs included in a combination of the high-<i>BRAF</i>V600E-scoring group and low-<i>RAS</i>-scoring group are categorized as BRAF-like PTCs (adjOR = 3.091, <i>p</i> = 0.001, 95% CI = 1.594–5.995). The different prediction models indicate variations in biological behavior between BRAF-like and RAS-like PTCs.https://www.mdpi.com/2227-9059/11/10/2803papillary thyroid carcinomaBRAF-likeRAS-like<i>BRAF</i>V600E<i>RAS</i> mutationprediction model |
| spellingShingle | 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 Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression Biomedicines papillary thyroid carcinoma BRAF-like RAS-like <i>BRAF</i>V600E <i>RAS</i> mutation prediction model |
| title | Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression |
| title_full | Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression |
| title_fullStr | Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression |
| title_full_unstemmed | Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression |
| title_short | Developing Models to Predict <i>BRAF</i>V600E and <i>RAS</i> Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression |
| title_sort | developing models to predict i braf i v600e and i ras i mutational status in papillary thyroid carcinoma using clinicopathological features and perk1 2 immunohistochemistry expression |
| topic | papillary thyroid carcinoma BRAF-like RAS-like <i>BRAF</i>V600E <i>RAS</i> mutation prediction model |
| url | https://www.mdpi.com/2227-9059/11/10/2803 |
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