c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules

Sara Tomei, Chiara Mazzanti, Ivo Marchetti, Leonardo Rossi, Katia Zavaglia, Francesca Lessi, Alessandro Apollo, Paolo Aretini, Giancarlo Di Coscio, Generoso Bevilacqua

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: A large amount of information has been collected on the molecular tumorigenesis of thyroid cancer. A low expression of c-KIT gene has been reported during the transformation of normal thyroid epithelium to papillary carcinoma suggesting a possible role of the gene in the differentiation of thyroid tissue rather than in the proliferation. The initial presentation of thyroid carcinoma is through a nodule and the best way nowadays to evaluate it is by fine-needle aspiration (FNA). However many thyroid FNAs are not definitively benign or malignant, yielding an indeterminate or suspicious diagnosis which ranges from 10 to 25% of FNAs. BRAF mutational analysis is commonly used to assess the malignancy of thyroid nodules but unfortunately it still leaves indeterminate diagnoses. The development of molecular initial diagnostic tests for evaluating a thyroid nodule is needed in order to define optimal surgical approach for patients with uncertain diagnosis pre- and intra-operatively.Methods: In this study we extracted RNA from 82 FNA smears, 46 malignant and 36 benign at the histology, in order to evaluate by quantitative Real Time PCR the expression levels of c-KIT gene.Results: We have found a highly preferential decrease rather than increase in transcript of c-KIT in malignant thyroid lesions compared to the benign ones. To explore the diagnostic utility of c-KIT expression in thyroid nodules, its expression values were divided in four arbitrarily defined classes, with class I characterized by the complete silencing of the gene. Class I and IV represented the two most informative groups, with 100% of the samples found malignant or benign respectively. The molecular analysis was proven by ROC (receiver operating characteristic) analysis to be highly specific and sensitive improving the cytological diagnostic accuracy of 15%.Conclusion: We propose the use of BRAF test (after uncertain cytological diagnosis) to assess the malignancy of thyroid nodules at first, then the use of the c-KIT expression to ultimately assess the diagnosis of the nodules that otherwise would remain suspicious. The c-KIT expression-based classification is highly accurate and may provide a tool to overcome the difficulties in today's preoperative diagnosis of thyroid suspicious malignancies.

Original languageEnglish
Article number7
JournalJournal of Translational Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - 10 Jan 2012
Externally publishedYes

Fingerprint

Thyroid Nodule
Thyroid Gland
Genes
Fine Needle Biopsy
Thyroid Neoplasms
Needles
Neoplasms
Histology
Molecular Pathology
Papillary Carcinoma
Gene Silencing
Routine Diagnostic Tests
ROC Curve
Real-Time Polymerase Chain Reaction
Carcinogenesis
Epithelium
RNA
Tissue

Keywords

  • c-kit
  • Fnac
  • Thyroid cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules. / Tomei, Sara; Mazzanti, Chiara; Marchetti, Ivo; Rossi, Leonardo; Zavaglia, Katia; Lessi, Francesca; Apollo, Alessandro; Aretini, Paolo; Di Coscio, Giancarlo; Bevilacqua, Generoso.

In: Journal of Translational Medicine, Vol. 10, No. 1, 7, 10.01.2012.

Research output: Contribution to journalArticle

Tomei, S, Mazzanti, C, Marchetti, I, Rossi, L, Zavaglia, K, Lessi, F, Apollo, A, Aretini, P, Di Coscio, G & Bevilacqua, G 2012, 'c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules', Journal of Translational Medicine, vol. 10, no. 1, 7. https://doi.org/10.1186/1479-5876-10-7
Tomei, Sara ; Mazzanti, Chiara ; Marchetti, Ivo ; Rossi, Leonardo ; Zavaglia, Katia ; Lessi, Francesca ; Apollo, Alessandro ; Aretini, Paolo ; Di Coscio, Giancarlo ; Bevilacqua, Generoso. / c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules. In: Journal of Translational Medicine. 2012 ; Vol. 10, No. 1.
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abstract = "Background: A large amount of information has been collected on the molecular tumorigenesis of thyroid cancer. A low expression of c-KIT gene has been reported during the transformation of normal thyroid epithelium to papillary carcinoma suggesting a possible role of the gene in the differentiation of thyroid tissue rather than in the proliferation. The initial presentation of thyroid carcinoma is through a nodule and the best way nowadays to evaluate it is by fine-needle aspiration (FNA). However many thyroid FNAs are not definitively benign or malignant, yielding an indeterminate or suspicious diagnosis which ranges from 10 to 25{\%} of FNAs. BRAF mutational analysis is commonly used to assess the malignancy of thyroid nodules but unfortunately it still leaves indeterminate diagnoses. The development of molecular initial diagnostic tests for evaluating a thyroid nodule is needed in order to define optimal surgical approach for patients with uncertain diagnosis pre- and intra-operatively.Methods: In this study we extracted RNA from 82 FNA smears, 46 malignant and 36 benign at the histology, in order to evaluate by quantitative Real Time PCR the expression levels of c-KIT gene.Results: We have found a highly preferential decrease rather than increase in transcript of c-KIT in malignant thyroid lesions compared to the benign ones. To explore the diagnostic utility of c-KIT expression in thyroid nodules, its expression values were divided in four arbitrarily defined classes, with class I characterized by the complete silencing of the gene. Class I and IV represented the two most informative groups, with 100{\%} of the samples found malignant or benign respectively. The molecular analysis was proven by ROC (receiver operating characteristic) analysis to be highly specific and sensitive improving the cytological diagnostic accuracy of 15{\%}.Conclusion: We propose the use of BRAF test (after uncertain cytological diagnosis) to assess the malignancy of thyroid nodules at first, then the use of the c-KIT expression to ultimately assess the diagnosis of the nodules that otherwise would remain suspicious. The c-KIT expression-based classification is highly accurate and may provide a tool to overcome the difficulties in today's preoperative diagnosis of thyroid suspicious malignancies.",
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AU - Zavaglia, Katia

AU - Lessi, Francesca

AU - Apollo, Alessandro

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AU - Di Coscio, Giancarlo

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