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. 2017 Mar 28;8(13):22023-22033.
doi: 10.18632/oncotarget.15786.

Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma

Lianghong Teng  1   2 , Wanglong Deng  3 , Junliang Lu  1 , Jing Zhang  1 , Xinyu Ren  1 , Huanli Duan  1 , Shannon Chuai  3 , Feidie Duan  3 , Wei Gao  2 , Tao Lu  1 , Huanwen Wu  1 , Zhiyong Liang  1
Affiliations

Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma

Lianghong Teng et al. Oncotarget. .

Abstract

Background: As a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear.

Results: The prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation.

Methods: HVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).

Conclusion: As an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.

Keywords: TERT promoter mutation; hobnail variant; molecular features; next-generation sequencing; papillary thyroid carcinoma.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Pathological findings of hobnail variant papillary thyroid carcinoma
(A) The papillary architecture and characteristic nuclear features of papillary carcinoma: pseudoinclusions and nuclear grooves. (B) Micropapillary structures lined by cuboidal cells with apically placed nuclei (“hobnail”appearance) and loss of cellular cohesion. (C) The papillary architecture with focal micropapillary areas at low magnification
Figure 2
Figure 2. Quality assessment of the targeted sequencing data among 75 samples
(A) Histogram show the percentage of all mapped reads and percentage of reads mapped to target regions for every sample. (B) Bar plot of The median coverage depth among all the target regions for each sample.
Figure 3
Figure 3. The association of DNA quality and total mutational load among all samples
(A) Violin plot in left panel show the number of selected mutations and selected low AF mutations between high-quality and low-quality samples. Boxplot in right panel show the insert size and library complexity between high-quality and low-quality samples. (B) Correlation between sample collection date and insert size, library complexity, number of mutations, number of low AF mutations illustrated by scatterplot
Figure 4
Figure 4. Mutational profiling of HVPTC compared with PTC and ATC/PDTC
(A) Heatmap of mutations for all samples grouped by subtype and data quality. (mutations are color-coded by AF) (B) Representation of the mutation status by Gene-level for all samples grouped by subtype
Figure 5
Figure 5
Detection of TERT promoter mutation (C228T) in RS1500212FFP by NGS (A) and Sanger sequencing (B), respectively
See this image and copyright information in PMC

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