Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

Yukinori Kurokawa, Nariaki Matsuura, Yutaka Kimura, Shinichi Adachi, Junya Fujita, Hiroshi Imamura, Kenji Kobayashi, Yuhki Yokoyama, Mohammed Nouri Shaker, Shuji Takiguchi, Masaki Mori, Yuichiro Doki

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Abstract

Background: Although some small-scale studies have suggested that human epidermal growth factor receptor 2 (HER2)-positive status in gastric cancer is associated with poor outcomes, the prognostic value of HER2 is still controversial. Since intratumoral HER2 heterogeneity is also an important issue, a multicenter large-scale study was conducted to evaluate the prognostic impacts of HER2 expression and intratumoral heterogeneity in gastric cancer. Methods: This study included 1,148 gastric cancer patients who underwent gastrectomy in 11 institutions. HER2 expression was centrally evaluated with immunohistochemistry and fluorescence in situ hybridization, and intratumoral HER2 heterogeneity was evaluated for HER2-positive tumors. Overall survival was compared between HER2-positive and HER2-negative patients and between the homogeneous and heterogeneous groups. Results: The HER2-positive rate was 15.7 %, and HER2 expression was significantly associated with histological type. HER2 expression scores obtained by immunohistochemistry showed a distinct influence on survival, and HER2-positive patients showed much poorer survival than HER2-negative patients [hazard ratio (HR) 1.59, 95 % confidence interval (CI) 1.24–2.02; P < 0.001). The subgroup analysis by pathological tumor stage showed a similar trend of poor survival in HER2-positive patients. Both intestinal type and diffuse type showed significant poor survival in HER2-positive patients. Cox multivariate analysis revealed that HER2 expression was an independent prognostic factor (HR 1.96, 95 % CI 1.51–2.55; P < 0.001). HER2 heterogeneity was observed in 75.4 % of HER2-positive cases, but the prognosis in the heterogeneous group was similar to that in the homogeneous group. Conclusions: Our study demonstrated that HER2 overexpression is an independent prognostic factor in patients with any stage of resectable gastric cancer. Intratumoral HER2 heterogeneity did not affect prognosis.

Original languageEnglish
Pages (from-to)691-697
Number of pages7
JournalGastric Cancer
Volume18
Issue number4
DOIs
Publication statusPublished - Oct 25 2015
Externally publishedYes

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Stomach Neoplasms
human ERBB2 protein
Survival
Immunohistochemistry
Confidence Intervals
Gastrectomy
Fluorescence In Situ Hybridization

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Kurokawa, Y., Matsuura, N., Kimura, Y., Adachi, S., Fujita, J., Imamura, H., ... Doki, Y. (2015). Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer. Gastric Cancer, 18(4), 691-697. https://doi.org/10.1007/s10120-014-0430-7

Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer. / Kurokawa, Yukinori; Matsuura, Nariaki; Kimura, Yutaka; Adachi, Shinichi; Fujita, Junya; Imamura, Hiroshi; Kobayashi, Kenji; Yokoyama, Yuhki; Shaker, Mohammed Nouri; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro.

In: Gastric Cancer, Vol. 18, No. 4, 25.10.2015, p. 691-697.

Research output: Contribution to journalArticle

Kurokawa, Y, Matsuura, N, Kimura, Y, Adachi, S, Fujita, J, Imamura, H, Kobayashi, K, Yokoyama, Y, Shaker, MN, Takiguchi, S, Mori, M & Doki, Y 2015, 'Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer', Gastric Cancer, vol. 18, no. 4, pp. 691-697. https://doi.org/10.1007/s10120-014-0430-7
Kurokawa, Yukinori ; Matsuura, Nariaki ; Kimura, Yutaka ; Adachi, Shinichi ; Fujita, Junya ; Imamura, Hiroshi ; Kobayashi, Kenji ; Yokoyama, Yuhki ; Shaker, Mohammed Nouri ; Takiguchi, Shuji ; Mori, Masaki ; Doki, Yuichiro. / Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer. In: Gastric Cancer. 2015 ; Vol. 18, No. 4. pp. 691-697.
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abstract = "Background: Although some small-scale studies have suggested that human epidermal growth factor receptor 2 (HER2)-positive status in gastric cancer is associated with poor outcomes, the prognostic value of HER2 is still controversial. Since intratumoral HER2 heterogeneity is also an important issue, a multicenter large-scale study was conducted to evaluate the prognostic impacts of HER2 expression and intratumoral heterogeneity in gastric cancer. Methods: This study included 1,148 gastric cancer patients who underwent gastrectomy in 11 institutions. HER2 expression was centrally evaluated with immunohistochemistry and fluorescence in situ hybridization, and intratumoral HER2 heterogeneity was evaluated for HER2-positive tumors. Overall survival was compared between HER2-positive and HER2-negative patients and between the homogeneous and heterogeneous groups. Results: The HER2-positive rate was 15.7 {\%}, and HER2 expression was significantly associated with histological type. HER2 expression scores obtained by immunohistochemistry showed a distinct influence on survival, and HER2-positive patients showed much poorer survival than HER2-negative patients [hazard ratio (HR) 1.59, 95 {\%} confidence interval (CI) 1.24–2.02; P < 0.001). The subgroup analysis by pathological tumor stage showed a similar trend of poor survival in HER2-positive patients. Both intestinal type and diffuse type showed significant poor survival in HER2-positive patients. Cox multivariate analysis revealed that HER2 expression was an independent prognostic factor (HR 1.96, 95 {\%} CI 1.51–2.55; P < 0.001). HER2 heterogeneity was observed in 75.4 {\%} of HER2-positive cases, but the prognosis in the heterogeneous group was similar to that in the homogeneous group. Conclusions: Our study demonstrated that HER2 overexpression is an independent prognostic factor in patients with any stage of resectable gastric cancer. Intratumoral HER2 heterogeneity did not affect prognosis.",
author = "Yukinori Kurokawa and Nariaki Matsuura and Yutaka Kimura and Shinichi Adachi and Junya Fujita and Hiroshi Imamura and Kenji Kobayashi and Yuhki Yokoyama and Shaker, {Mohammed Nouri} and Shuji Takiguchi and Masaki Mori and Yuichiro Doki",
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T1 - Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

AU - Kurokawa, Yukinori

AU - Matsuura, Nariaki

AU - Kimura, Yutaka

AU - Adachi, Shinichi

AU - Fujita, Junya

AU - Imamura, Hiroshi

AU - Kobayashi, Kenji

AU - Yokoyama, Yuhki

AU - Shaker, Mohammed Nouri

AU - Takiguchi, Shuji

AU - Mori, Masaki

AU - Doki, Yuichiro

PY - 2015/10/25

Y1 - 2015/10/25

N2 - Background: Although some small-scale studies have suggested that human epidermal growth factor receptor 2 (HER2)-positive status in gastric cancer is associated with poor outcomes, the prognostic value of HER2 is still controversial. Since intratumoral HER2 heterogeneity is also an important issue, a multicenter large-scale study was conducted to evaluate the prognostic impacts of HER2 expression and intratumoral heterogeneity in gastric cancer. Methods: This study included 1,148 gastric cancer patients who underwent gastrectomy in 11 institutions. HER2 expression was centrally evaluated with immunohistochemistry and fluorescence in situ hybridization, and intratumoral HER2 heterogeneity was evaluated for HER2-positive tumors. Overall survival was compared between HER2-positive and HER2-negative patients and between the homogeneous and heterogeneous groups. Results: The HER2-positive rate was 15.7 %, and HER2 expression was significantly associated with histological type. HER2 expression scores obtained by immunohistochemistry showed a distinct influence on survival, and HER2-positive patients showed much poorer survival than HER2-negative patients [hazard ratio (HR) 1.59, 95 % confidence interval (CI) 1.24–2.02; P < 0.001). The subgroup analysis by pathological tumor stage showed a similar trend of poor survival in HER2-positive patients. Both intestinal type and diffuse type showed significant poor survival in HER2-positive patients. Cox multivariate analysis revealed that HER2 expression was an independent prognostic factor (HR 1.96, 95 % CI 1.51–2.55; P < 0.001). HER2 heterogeneity was observed in 75.4 % of HER2-positive cases, but the prognosis in the heterogeneous group was similar to that in the homogeneous group. Conclusions: Our study demonstrated that HER2 overexpression is an independent prognostic factor in patients with any stage of resectable gastric cancer. Intratumoral HER2 heterogeneity did not affect prognosis.

AB - Background: Although some small-scale studies have suggested that human epidermal growth factor receptor 2 (HER2)-positive status in gastric cancer is associated with poor outcomes, the prognostic value of HER2 is still controversial. Since intratumoral HER2 heterogeneity is also an important issue, a multicenter large-scale study was conducted to evaluate the prognostic impacts of HER2 expression and intratumoral heterogeneity in gastric cancer. Methods: This study included 1,148 gastric cancer patients who underwent gastrectomy in 11 institutions. HER2 expression was centrally evaluated with immunohistochemistry and fluorescence in situ hybridization, and intratumoral HER2 heterogeneity was evaluated for HER2-positive tumors. Overall survival was compared between HER2-positive and HER2-negative patients and between the homogeneous and heterogeneous groups. Results: The HER2-positive rate was 15.7 %, and HER2 expression was significantly associated with histological type. HER2 expression scores obtained by immunohistochemistry showed a distinct influence on survival, and HER2-positive patients showed much poorer survival than HER2-negative patients [hazard ratio (HR) 1.59, 95 % confidence interval (CI) 1.24–2.02; P < 0.001). The subgroup analysis by pathological tumor stage showed a similar trend of poor survival in HER2-positive patients. Both intestinal type and diffuse type showed significant poor survival in HER2-positive patients. Cox multivariate analysis revealed that HER2 expression was an independent prognostic factor (HR 1.96, 95 % CI 1.51–2.55; P < 0.001). HER2 heterogeneity was observed in 75.4 % of HER2-positive cases, but the prognosis in the heterogeneous group was similar to that in the homogeneous group. Conclusions: Our study demonstrated that HER2 overexpression is an independent prognostic factor in patients with any stage of resectable gastric cancer. Intratumoral HER2 heterogeneity did not affect prognosis.

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