Dataset Information

Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing.

ABSTRACT:

Background

The follicular variant of papillary thyroid carcinoma (FVPTC) presents distinct histologic subtypes and molecular genotyping. The preoperative diagnosis of FVPTC through fine-needle aspiration cytology (FNAC) is challenging.

Methods

We reviewed 59 archival thyroid FNAC specimens of surgically confirmed FVPTC according to histologic subtype: encapsulated FVPTC (n = 30) and infiltrative FVPTC (n = 29). Galectin-3 immunostaining and molecular analyses for BRAF and three RAS genes (NRAS, HRAS, and KRAS) were performed.

Results

FNAC diagnoses of FVPTC included benign (5%), atypia of undetermined significance (19%), follicular neoplasm/suspicious for follicular neoplasm (14%), suspicious for PTC (29%), and PTC (34%). Galectin-3 immunostaining was positive in 50% of FNAC specimens. A BRAF mutation was found only in 14 (24%) tumors with the FNAC diagnosis of PTC or suspicious for PTC: 13 cases with the usual c.1799T>A (p.V600E) mutation and 1 case with a 3 base-pair deletion (c.1799_1801delTGA), resulting in a deletion of lysine at codon 601 and a deletion c.1799_1801delTGA that results in a valine-to-glutamate substitution at codon 600 (p.V600_K601>E) while preserving the reading frame. A BRAF K601E mutation was not found. RAS mutations were observed in 18 (33%) tumors (NRAS, 22%; HRAS, 6%; KRAS, 6%). Mutations of the three RAS genes were detected in codon 61 but not in codons 12 and 13. There was a decreasing trend of RAS mutation rates associated with an increasing risk of malignancy in the FNAC diagnostic categories. The triage efficacy of FNAC to make a recommendation for surgery was 73% for encapsulated tumors and 79% for infiltrative tumors. Addition of galectin-3 or the BRAF test to FNAC showed no significant improvement in the triage efficacy. However, RAS mutations significantly improved the triage efficacy of FNAC. There was no significant difference in the triage efficacy of FNAC, galectin-3 expression, and the prevalence of somatic mutations between encapsulated and infiltrative tumors.

Conclusion

Thyroid FNAC has a low sensitivity for the detection of FVPTC regardless of histologic subtype. Encapsulated FVPTC and infiltrative FVPTC have similar molecular profiles and rates of galectin-3 expression. RAS mutational analysis is more useful than BRAF testing to improve the triage efficacy of FNAC for FVPTC.

SUBMITTER: Lee SR

PROVIDER: S-EPMC3822389 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing.

Lee Sang Ryung SR Jung Chan Kwon CK Kim Tae Eun TE Bae Ja Seong JS Jung So Lyung SL Choi Yeong Jin YJ Kang Chang Suk CS

Thyroid : official journal of the American Thyroid Association 20130725 11

<h4>Background</h4>The follicular variant of papillary thyroid carcinoma (FVPTC) presents distinct histologic subtypes and molecular genotyping. The preoperative diagnosis of FVPTC through fine-needle aspiration cytology (FNAC) is challenging.<h4>Methods</h4>We reviewed 59 archival thyroid FNAC specimens of surgically confirmed FVPTC according to histologic subtype: encapsulated FVPTC (n = 30) and infiltrative FVPTC (n = 29). Galectin-3 immunostaining and molecular analyses for BRAF and three RA ...[more]

PMID: 23590130

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Project description:INTRODUCTION. Gene expression profiling has emerged as a potentially useful tool for personalized management of breast cancer. Adequate RNA can be obtained for this scope from dedicated fine-needle aspiration cytology (FNAC), with the limitation that separate sampling prohibits direct comparison with the material used for cytology. The aim of this study was to investigate whether syringe leftovers of cytological smears obtained in diagnostic FNACs can be successfully used to extract RNA for reliable PCR- and microarray-based gene expression analysis. METHODS. Twenty-eight FNACs were performed under ultrasound guide. After preparing two smears for cytological diagnosis, the syringes were immediately rinsed with Trizol® to extract RNA from residual material. The abundance and type of cells obtained from the smears was recorded and compared to RNA amounts and quality as determined by spectrophotometry and RT-PCR. FNAC leftovers of eleven breast cancers of different size, histological type, grade and immunoprofile were then selected for gene expression profiling using oligonucleotide microarrays. RESULTS. FNAC leftovers yielded an average of over 10 micrograms of RNA, more proportional to the amount of cells on the smear than to the lesion size, and adequate for expression analysis in 26/28 cases. The samples chosen for microarray analysis were clustered according to four criteria: (i) gene expression profiles of all detected genes; (ii) gene expression profiles of a previously defined stromal gene signature; (iii) “biological scores”, related to diagnostic cytological variables; (iv) “technical scores”, related to RNA/cRNA/microarray quality controls. Clusters generated by both expression profiles partitioned the samples in well-distinguished subgroups that were highly overlapping with clusters obtained using biological scores. Conversely, poor overlap was observed with clusters based on technical scores, demonstrating that sample divergences in RNA quality and amounts due to acquisition, handling and processing did not severely influence gene expression profiling. CONCLUSIONS. The syringe leftover after the smearing procedures of FNAC samples is suitable for RNA banking even when taken from small, non-palpable breast lesions, which guarantees congruity between morphological and molecular analysis. RNA yield mostly correlates with cellularity of the smears, and gene expression profiles are consistent with the cytologic features, and therefore with tumour biology.

Dataset Information

Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing.

Background

Methods

Results

Conclusion

Publications

Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing.

Similar Datasets

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