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

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.

• Authors: Vincenzo Catalano, Pasquale Mellone, Alfredo d'Avino, Viji Shridhar, Maria Pia Staccioli, Francesco Graziano, Paolo Giordani, David Rossi, Anna Maria Baldelli, Paolo Alessandroni, Daniele Santini, Laura Lorenzon, Enrica Testa, Silvia D'Emidio, Michele De Nictolis, Pietro Muretto, Stefano Luzi Fedeli, Alfonso Baldi
• Journal: Histopathology (Histopathology) Vol. 58 Issue 5 Pg. 669-78 (Apr 2011) ISSN: 1365-2559 [Electronic] England
• PMID: 21447133 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Limited.

Chemical References

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

Topics

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