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Ovarian Cancer
Increased STAT1 Expression in High Grade Serous Ovarian Cancer Is Associated With a Better Outcome
  1. Juliana A. Josahkian, MD, MSc*,
  2. Fabiano Pinto Saggioro, MD, PhD†,
  3. Thiago Vidotto, MSc*,
  4. Henrique Torres Ventura, PhD‡,
  5. Francisco José Candido dos Reis, MD, PhD§,
  6. Christiani Bisinoto de Sousa, MD, PhD§,
  7. Daniel Guimarães Tiezzi, MD, PhD§,
  8. Jurandyr Moreira de Andrade, MD, PhD§,
  9. Madhuri Koti, DVM, MVSc, PhD∥ and
  10. Jeremy A. Squire, PhD*,†,
  1. * Department of Genetics,
  2. † Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP;
  3. ‡ Brazilian Association of Zebu Breeders, Uberaba, MG;
  4. § Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; and
  5. ∥ Department of Biomedical and Molecular Sciences,
  6. Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
  1. Address correspondence and reprint requests to Jeremy A. Squire, PhD, Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada. E-mail: jsquireinsp{at}gmail.com.

Abstract

Objective Recently it has been demonstrated that constitutively activated signal transducer and activator of transcription 1 (STAT1) gene expression may act as a biomarker of ovarian cancer chemotherapy response. In this study, our objective was to validate the use of STAT1 immunohistochemistry as a prognostic biomarker for disease outcome using a cohort derived from Latin America.

Methods We evaluated a cohort of Brazilian high-grade serous ovarian cancer, comprising 65 patients with outcome data covering more than 5 years to determine the prognostic and predictive value of STAT1 expression levels. High-grade serous ovarian cancer tumors were used to construct a tissue microarray. Exploratory analyses were conducted on clinical, histopathological, and STAT1 expression data that included descriptive statistics and Pearson correlative analyses. Survival curves for disease-free survival and overall survival were obtained by the Kaplan-Meier method, and the significance of homogeneity between the classes was assessed by log-rank statistics (Mantel-Cox).

Results High expression of STAT1 in tumors was significantly associated with improved disease-free survival (P = 0.0256) and overall survival (P = 0.0193). Proportional hazards regression analysis showed STAT1 expression had an independent effect on both disease-free survival (P = 0.0358) and overall survival (P = 0.0469).

Conclusions These findings from a Brazilian cohort of patients with ovarian cancer reinforce the association of high STAT1 expression with better response to chemotherapy, providing additional validation of this protein as both a prognostic and predictive biomarker. Collectively, these results together with other recently published studies increase the feasibility of using the STAT1 pathway for the development of novel immunomodulator drugs that could enhance response to treatment.

  • Prognostic biomarker
  • Drug response
  • Tissue microarray
  • Immunohistochemistry

http://dx.doi.org/10.1097/IGC.0000000000001193

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    Footnotes

    • The authors declare no conflicts of interest.