Overexpression of trophoblast cell surface antigen 2 as an independent marker for a poor prognosis and as a potential therapeutic target in epithelial ovarian carcinoma

Int J Exp Pathol. 2016 Apr;97(2):150-8. doi: 10.1111/iep.12174. Epub 2016 Apr 29.

Abstract

Most patients with epithelial ovarian cancer (EOC) are diagnosed at an advanced stage, and therapeutic options for these patients are limited. The identification of suitable biomarkers could be helpful for patients with EOC, who might benefit from targeted therapies even in advanced stages of the disease. Trophoblast cell surface antigen 2 (TROP2) is highly expressed in various human malignant tumours; however, this has not been demonstrated clearly in EOC. In this study, we further evaluated whether TROP2 is a promising marker for EOC, and thus also a potential target for EOC immunotherapy. Quantitative real-time polymerase chain reaction (qPCR) and fluorescence-activated cell sorting (FACS) analysis were employed to determine TROP2 mRNA and protein expression in both human EOC and normal ovarian cell lines. Additionally, TROP2 protein expression was measured by immunohistochemistry in 128 EOC tissue samples, 21 normal ovarian tissues and 18 normal fallopian tubes. The correlations between TROP2 protein expression and patients' clinicopathological features were investigated, and survival outcomes were analysed. TROP2 mRNA and protein levels were upregulated significantly in EOC cell lines compared with normal cell lines. The protein of TROP2 was expressed in the majority of EOC tissue samples (90.6%) and overexpressed in 75 (58.6%) of the 128 tumour samples. TROP2 overexpression was correlated with relevant clinicopathological characteristics and was associated with significantly shortened overall survival and disease-free survival. Furthermore, TROP2 was an independent prognostic marker for EOCs as analysed by Cox regression. TROP2 was a potential biomarker for targeted therapy in patients with TROP2-overexpressing EOC.

Keywords: TROP2; biomarker targeted therapy; epithelial ovarian cancer; immunohistochemistry; independent prognostic marker.

MeSH terms

  • Adult
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Ovarian Epithelial
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / secondary
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / secondary
  • Prognosis
  • RNA, Messenger / genetics

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Neoplasm Proteins
  • RNA, Messenger
  • TACSTD2 protein, human