Dataset Information

Expression of Autophagy-Related Proteins in Hurthle Cell Neoplasm Is Different from That in Follicular Neoplasm.

ABSTRACT:

Purpose

We aimed to evaluate expression of autophagy-related proteins in Hürthle cell neoplasm (HCN) and follicular neoplasm (FN) and assess the clinical implications.

Methods

265 FNs (112 follicular carcinomas and 153 follicular adenomas) and 108 HCNs (27 Hürthle cell carcinomas and 81 Hürthle cell adenomas) were made into a tissue microarray. Immunohistochemical staining and Western blot for autophagy-related proteins (beclin-1, light chain (LC) 3A, LC3B, p62, and BNIP3) were performed, and the results were statistically analyzed.

Results

A higher expression rate of beclin-1, LC3B, p62, and BNIP3 was found in HCN than in FN (P < 0.001). The expression rate of beclin-1, LC3B, p62, and BNIP3 was the highest in HCCs followed by HCAs, FCs, and FAs in that order (P < 0.001). HCCs were positive for the largest number of autophagy-related proteins followed by HCAs, FCs, and FAs (P < 0.001), and most of the positive markers identified in HCCs were the high autophagy type (P < 0.001), defined by positive staining for three or more of the five autophagy-related proteins.

Conclusion

The autophagy-related proteins, beclin-1, LC3A, LC3B, p62, and BNIP3, were more frequently expressed in HCNs than in FNs, and HCCs showed the highest expression rate.

SUBMITTER: Cha YJ

PROVIDER: S-EPMC5551561 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Expression of Autophagy-Related Proteins in Hürthle Cell Neoplasm Is Different from That in Follicular Neoplasm.

Cha Yoon Jin YJ Kim Hye Min HM Koo Ja Seung JS

Disease markers 20170727

<h4>Purpose</h4>We aimed to evaluate expression of autophagy-related proteins in Hürthle cell neoplasm (HCN) and follicular neoplasm (FN) and assess the clinical implications.<h4>Methods</h4>265 FNs (112 follicular carcinomas and 153 follicular adenomas) and 108 HCNs (27 Hürthle cell carcinomas and 81 Hürthle cell adenomas) were made into a tissue microarray. Immunohistochemical staining and Western blot for autophagy-related proteins (beclin-1, light chain (LC) 3A, LC3B, p62, and BNIP3) were pe ...[more]

PMID: 28819333

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Project description:BACKGROUND:Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. METHODS:The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. RESULTS:In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor ? (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). CONCLUSIONS:The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.