HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer

Histopathology. 2011 Apr;58(5):669-78. doi: 10.1111/j.1365-2559.2011.03818.x. Epub 2011 Mar 30.

Abstract

Aims: HtrA1 is a member of the HtrA (high-temperature requirement factor A) family of serine proteases. HtrA1 plays a protective role in various malignancies due to its tumour suppressive properties. The aim of this study was to determine HtrA1 expression as a predictor of chemoresponse in patients with advanced gastric cancer.

Methods and results: HtrA1 expression was determined by immunohistochemistry on specimens of primary gastric cancer from 80 patients treated consecutively with cisplatin-based combination chemotherapy. Response to chemotherapy was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Our population consisted of males/females [51/29; median age 64 years (range 32-82)]. A complete or partial response was observed in 71.4% [95% confidence interval (CI) 54.7-88.2], 66.7% (95% CI 47.8-85.5) and 28.6% (95 CI 11.8-45.3) of tumours showing high, medium and low HtrA1 expression, respectively. A statistically significant association between HtrA1 expression and the clinical response was observed (P = 0.002). The median overall survival for patients with high/medium expression was 17 months compared to 9.5 months for patients with low HtrA1 expression (P = 0.037).

Conclusions: Identification of HtrA1 in gastric cancer prior to chemotherapy indicates that levels of HtrA1 could be used to predict response to platinum-based combination therapies. Further assessment of HtrA1 expression is highly warranted in large, prospective studies.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage*
  • Cisplatin / therapeutic use
  • Female
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Male
  • Middle Aged
  • Serine Endopeptidases / metabolism*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / mortality
  • Survival Analysis

Substances

  • High-Temperature Requirement A Serine Peptidase 1
  • HTRA1 protein, human
  • Serine Endopeptidases
  • Cisplatin