Research Papers:

Expression of glutamine metabolism-related proteins in thyroid cancer

Hye Min Kim, Yu Kyung Lee and Ja Seung Koo _

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Oncotarget. 2016; 7:53628-53641. https://doi.org/10.18632/oncotarget.10682

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Hye Min Kim1, Yu Kyung Lee1, Ja Seung Koo1

1Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea

Correspondence to:

Ja Seung Koo, email: kjs1976@yuhs.ac

Keywords: thyroid cancer, glutamine, metabolism, stroma, pathology

Received: February 01, 2016     Accepted: July 09, 2016     Published: July 18, 2016


Purpose: This study aimed to investigate the expression of glutamine metabolism-related protein in tumor and stromal compartments among the histologic subtypes of thyroid cancer.

Results: GLS1 and GDH expression in tumor and stromal compartments were the highest in AC than in other subtypes. Tumoral ASCT2 expression was higher in MC but lower in FC (p < 0.001). In PTC, tumoral GLS1 and tumoral GDH expression was higher in the conventional type than in the follicular variant (p = 0.043 and 0.001, respectively), and in PTC with BRAF V600E mutation than in PTC without BRAF V600E mutation (p<0.001). Stromal GDH positivity was the independent factor associated with short overall survival (hazard ratio: 21.48, 95% confidence interval: 2.178-211.8, p = 0.009).

Methods: We performed tissue microarrays with 557 thyroid cancer cases (papillary thyroid carcinoma [PTC]: 344, follicular carcinoma [FC]: 112, medullary carcinoma [MC]: 70, poorly differentiated carcinoma [PDC]: 23, and anaplastic carcinoma [AC]: 8) and 152 follicular adenoma (FA) cases. We performed immunohistochemical staining of glutaminolysis-related proteins (glutaminase 1 [GLS1], glutamate dehydrogenase [GDH], and amino acid transporter-2 [ASCT-2]).

Conclusion: Glutamine metabolism-related protein expression differed among the histologic subtypes of thyroid cancer.

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