Association between STAT1 activity and BRAF mutations in papillary thyroid carcinomas

J Surg Oncol. 2012 Nov;106(6):719-23. doi: 10.1002/jso.23125. Epub 2012 Apr 18.

Abstract

Background: Signal transducer and activator of transcription-1 (STAT1) plays a critical role in tumorigenesis by controlling several functions in both tumor cells and the immune system, and is considered to be a tumor suppressor. The present study evaluated the activity of STAT1 in human papillary thyroid carcinomas (PTC).

Methods: STAT1 activity was measured in nuclear extracts of tumor tissues from 35 PTC patients using an ELISA-based kit.

Results: STAT1 activity was significantly lower in tumors than in the surrounding normal thyroid tissues (P < 0.01). The association between STAT1 activity and clinicopathologic factors was analyzed in PTC tissues. STAT1 activity was significantly lower in tumors that measured 2 cm or more than in tumors that measured 2 cm or less (P = 0.044). Moreover, tumor size was inversely correlated with STAT1 activity (Spearman's rank correlation coefficient (rho) = -0.34, P = 0.048). In addition, tumors with BRAF mutations showed lower STAT1 activity than wild-type BRAF tumors [0.064 (0.056-0.124) vs. 0.108 (0.073-0.153) arbitrary units, P = 0.048].

Conclusion: STAT1 activity is suppressed in PTCs (as measured by DNA-binding activities). The tumor with T1799A BRAF mutation and tumor sizes of 2 cm or more were clinicopathologic parameters associated with lower STAT1 activity. STAT1 activity of tumor might be one of potential biomarkers for PTC's.

MeSH terms

  • Adult
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma, Papillary
  • DNA / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Reagent Kits, Diagnostic
  • STAT1 Transcription Factor / metabolism*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism

Substances

  • Reagent Kits, Diagnostic
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • DNA
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf