Relevance of BRAF(V600E) mutation testing versus RAS point mutations and RET/PTC rearrangements evaluation in the diagnosis of thyroid cancer.

Abstract

BACKGROUND:

A molecular profile including BRAF and RAS mutations as well as RET/PTC rearrangement evaluation has been proposed to provide an accurate presurgical assessment of thyroid nodules and to reduce the number of unnecessary diagnostic surgeries, sparing patients' health and saving healthcare resources. However, the application of such molecular analyses may provide different results among different centers and populations in real-life settings. Our aims were to evaluate the diagnostic utility of assessing the presence of BRAF and RAS mutations and RET/PTC1 and RET/PTC3 rearrangements in all cytological categories in an Italian group of thyroid nodule patients assessed prospectively, and to understand whether and which mutation testing might be helpful in cytologically indeterminate nodules.

METHODS:

A total of 911 patients were submitted to ultrasound and fine-needle aspiration biopsy examination. Cytological evaluation was performed in parallel with molecular testing and compared to pathological results in 940 thyroid nodules, including 140 indeterminate lesions.

RESULTS:

BRAF mutation testing provided the best contribution to cancer diagnosis, allowing the disease to be detected at an early stage, and identifying indeterminate nodules in which diagnostic lobectomy could be spared. On the contrary, RAS and RET/PTC analysis did not further increase diagnostic sensitivity for thyroid cancer. In addition, we found RET/PTC rearrangements in benign lesions, indicating that this molecular marker might not be useful for the detection of thyroid cancer.

CONCLUSION:

BRAF(V600E) mutation analysis is superior to RAS point mutations and evaluation of RET/PTC rearrangements in the diagnosis of thyroid cancer, even in indeterminate lesions.

• Authors: Martina Rossi, Mattia Buratto, Federico Tagliati, Roberta Rossi, Sabrina Lupo, Giorgio Trasforini, Giovanni Lanza, Paola Franceschetti, Stefania Bruni, Ettore Degli Uberti, Maria Chiara Zatelli
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 25 Issue 2 Pg. 221-8 (Feb 2015) ISSN: 1557-9077 [Electronic] United States
• PMID: 25333496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-ret
• RET protein, human
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• ras Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• DNA Mutational Analysis
• Female
• Gene Rearrangement
• Humans
• Male
• Middle Aged
• Mutation
• Proto-Oncogene Proteins B-raf (genetics)
• Proto-Oncogene Proteins c-ret (genetics)
• Sensitivity and Specificity
• Thyroid Neoplasms (diagnosis, genetics, pathology)
• ras Proteins (genetics)