Molecular characterization of tumors meeting diagnostic criteria for the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

Pool, Christopher; Walter, Vonn; Bann, Darrin V.; Goldenberg, David; Broach, James R.; Hennessy, Max; Washburn, Erik; Williams, Nicole; Crist, Henry; Imamura, Yuka; Warrick, Joshua I.

doi:10.1007/s00428-018-02512-6

Cited by 12 publications

(12 citation statements)

References 42 publications

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“…As described for FTA and FTC, NRAS codon 61 mutations and PAX8/PPARG are the most common abnormality observed in FVPTC. Although the NRAS mutation is a very prevalent event in follicular thyroid lesions, this mutation does not show a statistical correlation with any specific lesion, as previously observed (21, 27, 30, 42, 45).…”

Section: Discussionsupporting

confidence: 44%

“…Importantly, all samples that harbored the BRAF V600E mutation were I-EFVPTC or IFVPTC when reviewed by two experienced pathologists who were blinded to the mutation status, which corroborates the more aggressive phenotype associated with the BRAF V600E mutation. Two cases had BRAF V600E co-occurring with NRAS Q61R, a correlation widely described in the literature (17, 23, 26, 30, 45, 46, 47, 48, 49). No EFVPTC or NIFTP had BRAF mutations.…”

Section: Discussionmentioning

confidence: 53%

“…As expected, mutations in RAS (mainly in codon 61 of NRAS and HRAS ) are the most prevalent mutations found in NIFTP. PAX8/PPARG and THADA fusions and EIF2AX and BRAF K601 mutations were recently described in a small portion of NIFTPs (30, 31). The presence of the BRAF-V600E mutation may be a hint toward the presence of more aggressive histological features or even the presence of papillae and help to exclude the diagnosis of NIFTP (18, 26, 31, 32, 33, 34, 35, 36).…”

Section: Introductionmentioning

confidence: 99%

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Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior

Paniza

Mendes

Viana

et al. 2019

Endocrine Connections

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The recent reclassification of a follicular variant of papillary thyroid carcinoma (FVPTC), subset as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), aims to avoid overtreatment of patients with an indolent lesion. The diagnosis of NIFTP has recently been revisited using more rigid criteria. This study presents histological and molecular findings and a long clinical follow-up of 94 FVPTC, 40 cases of follicular adenoma (FTA) and 22 cases of follicular carcinoma (FTC) that were classified before the advent of the NIFTP reclassification. All slides were reviewed using these rigid criteria and analysis of numerous sections of paraffin blocks and reclassified as 7 NIFTPs, 2 EFVPTCs, 29 infiltrative FVPTC (IFVPTCs), 57 invasive EFVPTC (I-EFVPTCs), 39 FTAs and 22 FTCs. Remarkably, EFVPTC and NIFTP patients were all free of disease at the end of follow-up and showed no BRAF mutation. Only one NIFTP sample harbored mutations, an NRAS Q61R. PAX8/PPARG fusion was found in I-EFVPTCs and FTC. Although additional studies are needed to identify a specific molecular profile to aid in the diagnosis of lesions with borderline morphological characteristics, we confirmed that the BRAF V600E mutation is an important tool to exclude the diagnosis of NIFTP. We also show that rigorous histopathological criteria should be strongly followed to avoid missing lesions in which more aggressive behavior is present, mainly via the analysis of capsule or vascular invasion and the presence of papillary structures.

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Section: Discussionsupporting

confidence: 44%

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

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Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior

Paniza

Mendes

Viana

et al. 2019

Endocrine Connections

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“…30e32 Most of these cases had results that were characterized as suspicious; however, it is difficult to assess whether among not-operated Gene Expression Classifier benign nodules there were indolent tumors as NIFTPs. It was already demonstrated that NIFTP can be either FA like or FVPTC like, based on mRNA and miRNA expression patterns obtained by analyzing formalin-fixed, paraffinembedded samples 9,23,33 : in this study, these findings were confirmed on FNA samples. Assuming that NIFTPs are intrinsically heterogeneous, it is an important issue regarding their inclusion in the training sets of molecular tests.…”

Section: Discussionsupporting

confidence: 76%

Digital Gene Expression Analysis on Cytology Smears Can Rule Out Malignancy in Follicular-Patterned Thyroid Tumors

Macerola

Poma

Proietti

et al. 2020

The Journal of Molecular Diagnostics

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it.Patients with indeterminate thyroid nodules (Bethesda III and IV) are often treated with diagnostic lobectomy, which in most cases represents an overtreatment. A reliable rule-out molecular test could spare patients unnecessary surgery. Stained smears of 88 indeterminate thyroid nodules with histologic diagnosis of follicular-patterned tumors were selected: 34 follicular adenomas (FAs), 34 follicular variant papillary thyroid carcinomas (FVPTCs), and 20 noninvasive follicular neoplasms with papillarylike nuclear features (NIFTPs). The expression level of 126 genes was measured by digital counting. Mutation testing was performed for the main gene mutations and fusions. Performance of gene expression and mutation tests was calculated by receiver operating characteristic analysis. The gene expression model showed an area under the curve (AUC) of 88%, with 91% negative predictive value in FAs and FVPTCs only. Part of NIFTPs was labeled as benign, and part was labeled as malignant; thus, the classifier performance worsened. Two FAs (5.9%), eight NIFTPs (40%), and 22 FVPTCs (64.7%) were mutation positive. Mutation testing AUC was 79% in FAs and FVPTCs, and decreased by including NIFTPs. This gene expressionebased test was feasible in thyroid-stained smears, showed higher AUC than mutation test, and had a high negative predictive valuedmaking it a good candidate as a rule-out test for indeterminate thyroid cytology. NIFTPs have a heterogeneous phenotype, and their preoperative diagnosis requires further investigation.

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“…TCGA data was limited in this regard as FVPTC patients were not further classified into subtypes. We looked to sequencing data from a previous study, Pool et al [15], and performed differential expression analysis on niFVPTC vs iFVPTC samples (Figure S1). The genotypes of both sub-variants were similar, as evidenced by the small number of differentially expressed genes.…”

Section: Resultsmentioning

confidence: 99%

Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes

Chakladar

Bouvet

et al. 2019

Cancers

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Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This study aims to characterize dysregulated immune-associated and cancer-associated genes in three PTC subtypes to explore how the interplay between cancer and immune processes causes differential prognosis. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to identify dysregulated genes in each variant. The dysregulation profiles of the subtypes were compared using functional pathways clustering and correlations to relevant clinical variables, genomic alterations, and microRNA regulation. We discovered that the dysregulation profiles of classical PTC (CPTC) and the tall cell variant (TCPTC) are similar and are distinct from that of the follicular variant (FVPTC). However, unique cancer or immune-associated genes are associated with clinical variables for each subtype. Cancer-related genes MUC1, FN1, and S100-family members were the most clinically relevant in CPTC, while APLN and IL16, both immune-related, were clinically relevant in FVPTC. RAET-family members, also immune-related, were clinically relevant in TCPTC. Collectively, our data suggest that dysregulation of both cancer and immune associated genes defines the gene expression landscapes of PTC variants, but different cancer or immune related genes may drive the phenotype of each variant.

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Molecular characterization of tumors meeting diagnostic criteria for the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

Cited by 12 publications

References 42 publications

Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior

Revised criteria for diagnosis of NIFTP reveals a better correlation with tumor biological behavior

Digital Gene Expression Analysis on Cytology Smears Can Rule Out Malignancy in Follicular-Patterned Thyroid Tumors

Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes

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