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

Vincenzo Catalano, Pasquale Mellone, Alfredo d'Avino, Vijayalakshmi 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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 64years (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 17months compared to 9.5months 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.

Original languageEnglish (US)
Pages (from-to)669-678
Number of pages10
JournalHistopathology
Volume58
Issue number5
DOIs
StatePublished - Apr 2011

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Combination Drug Therapy
Cisplatin
Stomach Neoplasms
Confidence Intervals
Drug Therapy
Neoplasms
Serine Proteases
Platinum
Immunohistochemistry
Prospective Studies
Temperature
Survival
Population
Therapeutics

Keywords

  • Chemoresistance
  • Chemotherapy
  • Cisplatin
  • Gastric cancer
  • HtrA1

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer. / Catalano, Vincenzo; Mellone, Pasquale; d'Avino, Alfredo; Shridhar, Vijayalakshmi; Staccioli, Maria Pia; Graziano, Francesco; Giordani, Paolo; Rossi, David; Baldelli, Anna Maria; Alessandroni, Paolo; Santini, Daniele; Lorenzon, Laura; Testa, Enrica; D'Emidio, Silvia; De Nictolis, Michele; Muretto, Pietro; Fedeli, Stefano Luzi; Baldi, Alfonso.

In: Histopathology, Vol. 58, No. 5, 04.2011, p. 669-678.

Research output: Contribution to journalArticle

Catalano, V, Mellone, P, d'Avino, A, Shridhar, V, Staccioli, MP, Graziano, F, Giordani, P, Rossi, D, Baldelli, AM, Alessandroni, P, Santini, D, Lorenzon, L, Testa, E, D'Emidio, S, De Nictolis, M, Muretto, P, Fedeli, SL & Baldi, A 2011, 'HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer', Histopathology, vol. 58, no. 5, pp. 669-678. https://doi.org/10.1111/j.1365-2559.2011.03818.x
Catalano, Vincenzo ; Mellone, Pasquale ; d'Avino, Alfredo ; Shridhar, Vijayalakshmi ; Staccioli, Maria Pia ; Graziano, Francesco ; Giordani, Paolo ; Rossi, David ; Baldelli, Anna Maria ; Alessandroni, Paolo ; Santini, Daniele ; Lorenzon, Laura ; Testa, Enrica ; D'Emidio, Silvia ; De Nictolis, Michele ; Muretto, Pietro ; Fedeli, Stefano Luzi ; Baldi, Alfonso. / HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer. In: Histopathology. 2011 ; Vol. 58, No. 5. pp. 669-678.
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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 64years (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 17months compared to 9.5months 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.",
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AU - Catalano, Vincenzo

AU - Mellone, Pasquale

AU - d'Avino, Alfredo

AU - Shridhar, Vijayalakshmi

AU - Staccioli, Maria Pia

AU - Graziano, Francesco

AU - Giordani, Paolo

AU - Rossi, David

AU - Baldelli, Anna Maria

AU - Alessandroni, Paolo

AU - Santini, Daniele

AU - Lorenzon, Laura

AU - Testa, Enrica

AU - D'Emidio, Silvia

AU - De Nictolis, Michele

AU - Muretto, Pietro

AU - Fedeli, Stefano Luzi

AU - Baldi, Alfonso

PY - 2011/4

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N2 - 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 64years (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 17months compared to 9.5months 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.

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KW - Chemotherapy

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