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

Catalano V, Mellone P, d’Avino A, Shridhar V, Staccioli M P, Graziano F, Giordani P, Rossi D, Baldelli A M, Alessandroni P, Santini D, Lorenzon L, Testa E, D’Emidio S, De Nictolis M, Muretto P, Fedeli S L & Baldi A (2011) Histopathology58, 669–678 HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer 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.