Molecular characterization of tumors meeting diagnostic criteria for the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).
Publication/Presentation Date
3-1-2019
Abstract
"Follicular variant" papillary thyroid carcinomas (FV-PTC) that do not histologically invade have a miniscule risk of metastasis, and thus been reclassified as a tumor of low malignant potential, the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). There are few molecular studies of this tumor type. We performed gene expression analysis, by RNA sequencing, on a series of FV-PTCs, NIFTPs, and follicular adenomas. A training set comprised tumors from The Cancer Genome Atlas (TCGA) repository (n = 46), digital slides from which were reviewed and classified as invasive or non-invasive FV-PTC. A validation set comprised in-house NIFTPs, invasive FV-PTCs, and follicular adenomas (n = 26). In the training set, unsupervised clustering separated tumors into three distinct expression subtypes, which associated with invasion and characteristic molecular alterations. Specifically, the "BRAF-like" subtype was enriched in invasive FV-PTCs and tumors with BRAF V600E mutations. The "THADA-like" subtype was enriched in non-invasive tumors and those with rearrangements involving THADA. The "RAS-family-like" subtype included many invasive and non-invasive FV-PTCs and was enriched in tumors with mutations in RAS family genes. In the validation set, nearest centroid analysis classified all invasive FV-PTCs as "BRAF-like" and all follicular adenomas as either "RAS-like" or "THADA-like." NIFTPs were the most molecularly diverse histologic type, with cases classified as "BRAF-like," "THADA-like," and "RAS-family-like." In conclusion, tumors fitting criteria for NIFTP are molecularly diverse, making it difficult to diagnose them with molecular studies, likely including matrial from cytopathology samples.
Volume
474
Issue
3
First Page
341
Last Page
351
ISSN
1432-2307
Published In/Presented At
Pool, C., Walter, V., Bann, D., Goldenberg, D., Broach, J., Hennessy, M., Cottrill, E., Washburn, E., Williams, N., Crist, H., Imamura, Y., & Warrick, J. I. (2019). Molecular characterization of tumors meeting diagnostic criteria for the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Virchows Archiv : an international journal of pathology, 474(3), 341–351. https://doi.org/10.1007/s00428-018-02512-6
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
30645670
Department(s)
Administration and Leadership
Document Type
Article