New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee

Tetsuji Sawada, Masakazu Yashiro, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Kohji Miyazaki, Keita Kai, Sachio Fushida, Takashi Fujimura, Masaichi Ohira, Yoshihiro Kakeji, Shoji Natsugoe, Ken Shirabe, Sachiyo Nomura, Yutaka Shimada, Naohiro Tomita, Kosei Hirakawa, Yoshihiko Maehara

Research output: Contribution to journalArticle

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Abstract

Background: The G-Project committee was erected by the Japan Society for Gastroenterological Carcinogenesis with an aim of establishing a new classification scheme based on molecular biological characteristics that would supplement the conventional TNM classification to better predict outcome.

Methods: In a literature search involving 822 articles on gastric cancer, eight molecules including p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, matrix metalloproteinase-7 (MMP-7), human epidermal growth factor receptor 2, Regenerating islet-derived family, member 4, olfactomedin-4 and Claudin-18 were selected as candidates to be included in the new molecular classification scheme named G-factor. A total of 210 cases of gastric cancer who underwent curative R0 resection were registered from four independent facilities. Immunohistochemical staining for the aforementioned molecules was performed for the surgically resected specimens of the 210 cases to investigate the correlation between clinicopathological factors and expression of each molecule.

Results: No significant correlation was observed between the immunostaining expression of any of the eight factors and postoperative recurrence. However, the expressions of p53 and MMP-7 were significantly correlated with overall survival (OS). When 210 gastric cancer patients were divided into three groups based on the expression of p53 and MMP-7 (G0 group: negative for both p53 and MMP-7, n = 69, G1 group: positive for either p53 or MMP-7, n = 97, G2 group: positive for both of the molecules, n = 44), G2 group demonstrated significantly higher recurrence rate (59 %) compared to 38 % in G0 (p = 0.047). The multivariate regression analysis revealed that G2 group was independently associated with a shorter disease-free survival (DFS) (hazard ratio 1.904, 95 % CI 1.098–3.303; p = 0.022), although the association with OS was not significant. Stage II patients among the G2 group had significantly inferior prognosis both in terms of OS and DFS when compared with those among the G0/G1 group, with survival curves similar to those of Stage III cases.

Conclusions: G-factor based on the expression of p53 and MMP-7 was found to be a promising factor to predict outcome of Stage II/III gastric cancer, and possibly to help select the treatment for Stage II cancer, thus supplementing the conventional TNM system.

Original languageEnglish
Pages (from-to)119-128
Number of pages10
JournalGastric Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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Matrix Metalloproteinase 7
Neoplasm Staging
Stomach Neoplasms
Japan
Carcinogenesis
Research
Survival
Disease-Free Survival
Claudin-4
Vascular Endothelial Growth Factor C
Recurrence
Vascular Endothelial Growth Factor A
Multivariate Analysis
Regression Analysis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

New molecular staging with G-factor supplements TNM classification in gastric cancer : a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee. / Sawada, Tetsuji; Yashiro, Masakazu; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Miyazaki, Kohji; Kai, Keita; Fushida, Sachio; Fujimura, Takashi; Ohira, Masaichi; Kakeji, Yoshihiro; Natsugoe, Shoji; Shirabe, Ken; Nomura, Sachiyo; Shimada, Yutaka; Tomita, Naohiro; Hirakawa, Kosei; Maehara, Yoshihiko.

In: Gastric Cancer, Vol. 18, No. 1, 01.01.2015, p. 119-128.

Research output: Contribution to journalArticle

Sawada, T, Yashiro, M, Sentani, K, Oue, N, Yasui, W, Miyazaki, K, Kai, K, Fushida, S, Fujimura, T, Ohira, M, Kakeji, Y, Natsugoe, S, Shirabe, K, Nomura, S, Shimada, Y, Tomita, N, Hirakawa, K & Maehara, Y 2015, 'New molecular staging with G-factor supplements TNM classification in gastric cancer: a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee', Gastric Cancer, vol. 18, no. 1, pp. 119-128. https://doi.org/10.1007/s10120-014-0338-2
Sawada, Tetsuji ; Yashiro, Masakazu ; Sentani, Kazuhiro ; Oue, Naohide ; Yasui, Wataru ; Miyazaki, Kohji ; Kai, Keita ; Fushida, Sachio ; Fujimura, Takashi ; Ohira, Masaichi ; Kakeji, Yoshihiro ; Natsugoe, Shoji ; Shirabe, Ken ; Nomura, Sachiyo ; Shimada, Yutaka ; Tomita, Naohiro ; Hirakawa, Kosei ; Maehara, Yoshihiko. / New molecular staging with G-factor supplements TNM classification in gastric cancer : a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee. In: Gastric Cancer. 2015 ; Vol. 18, No. 1. pp. 119-128.
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abstract = "Background: The G-Project committee was erected by the Japan Society for Gastroenterological Carcinogenesis with an aim of establishing a new classification scheme based on molecular biological characteristics that would supplement the conventional TNM classification to better predict outcome.Methods: In a literature search involving 822 articles on gastric cancer, eight molecules including p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, matrix metalloproteinase-7 (MMP-7), human epidermal growth factor receptor 2, Regenerating islet-derived family, member 4, olfactomedin-4 and Claudin-18 were selected as candidates to be included in the new molecular classification scheme named G-factor. A total of 210 cases of gastric cancer who underwent curative R0 resection were registered from four independent facilities. Immunohistochemical staining for the aforementioned molecules was performed for the surgically resected specimens of the 210 cases to investigate the correlation between clinicopathological factors and expression of each molecule.Results: No significant correlation was observed between the immunostaining expression of any of the eight factors and postoperative recurrence. However, the expressions of p53 and MMP-7 were significantly correlated with overall survival (OS). When 210 gastric cancer patients were divided into three groups based on the expression of p53 and MMP-7 (G0 group: negative for both p53 and MMP-7, n = 69, G1 group: positive for either p53 or MMP-7, n = 97, G2 group: positive for both of the molecules, n = 44), G2 group demonstrated significantly higher recurrence rate (59 {\%}) compared to 38 {\%} in G0 (p = 0.047). The multivariate regression analysis revealed that G2 group was independently associated with a shorter disease-free survival (DFS) (hazard ratio 1.904, 95 {\%} CI 1.098–3.303; p = 0.022), although the association with OS was not significant. Stage II patients among the G2 group had significantly inferior prognosis both in terms of OS and DFS when compared with those among the G0/G1 group, with survival curves similar to those of Stage III cases.Conclusions: G-factor based on the expression of p53 and MMP-7 was found to be a promising factor to predict outcome of Stage II/III gastric cancer, and possibly to help select the treatment for Stage II cancer, thus supplementing the conventional TNM system.",
author = "Tetsuji Sawada and Masakazu Yashiro and Kazuhiro Sentani and Naohide Oue and Wataru Yasui and Kohji Miyazaki and Keita Kai and Sachio Fushida and Takashi Fujimura and Masaichi Ohira and Yoshihiro Kakeji and Shoji Natsugoe and Ken Shirabe and Sachiyo Nomura and Yutaka Shimada and Naohiro Tomita and Kosei Hirakawa and Yoshihiko Maehara",
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TY - JOUR

T1 - New molecular staging with G-factor supplements TNM classification in gastric cancer

T2 - a multicenter collaborative research by the Japan Society for Gastroenterological Carcinogenesis G-Project committee

AU - Sawada, Tetsuji

AU - Yashiro, Masakazu

AU - Sentani, Kazuhiro

AU - Oue, Naohide

AU - Yasui, Wataru

AU - Miyazaki, Kohji

AU - Kai, Keita

AU - Fushida, Sachio

AU - Fujimura, Takashi

AU - Ohira, Masaichi

AU - Kakeji, Yoshihiro

AU - Natsugoe, Shoji

AU - Shirabe, Ken

AU - Nomura, Sachiyo

AU - Shimada, Yutaka

AU - Tomita, Naohiro

AU - Hirakawa, Kosei

AU - Maehara, Yoshihiko

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: The G-Project committee was erected by the Japan Society for Gastroenterological Carcinogenesis with an aim of establishing a new classification scheme based on molecular biological characteristics that would supplement the conventional TNM classification to better predict outcome.Methods: In a literature search involving 822 articles on gastric cancer, eight molecules including p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, matrix metalloproteinase-7 (MMP-7), human epidermal growth factor receptor 2, Regenerating islet-derived family, member 4, olfactomedin-4 and Claudin-18 were selected as candidates to be included in the new molecular classification scheme named G-factor. A total of 210 cases of gastric cancer who underwent curative R0 resection were registered from four independent facilities. Immunohistochemical staining for the aforementioned molecules was performed for the surgically resected specimens of the 210 cases to investigate the correlation between clinicopathological factors and expression of each molecule.Results: No significant correlation was observed between the immunostaining expression of any of the eight factors and postoperative recurrence. However, the expressions of p53 and MMP-7 were significantly correlated with overall survival (OS). When 210 gastric cancer patients were divided into three groups based on the expression of p53 and MMP-7 (G0 group: negative for both p53 and MMP-7, n = 69, G1 group: positive for either p53 or MMP-7, n = 97, G2 group: positive for both of the molecules, n = 44), G2 group demonstrated significantly higher recurrence rate (59 %) compared to 38 % in G0 (p = 0.047). The multivariate regression analysis revealed that G2 group was independently associated with a shorter disease-free survival (DFS) (hazard ratio 1.904, 95 % CI 1.098–3.303; p = 0.022), although the association with OS was not significant. Stage II patients among the G2 group had significantly inferior prognosis both in terms of OS and DFS when compared with those among the G0/G1 group, with survival curves similar to those of Stage III cases.Conclusions: G-factor based on the expression of p53 and MMP-7 was found to be a promising factor to predict outcome of Stage II/III gastric cancer, and possibly to help select the treatment for Stage II cancer, thus supplementing the conventional TNM system.

AB - Background: The G-Project committee was erected by the Japan Society for Gastroenterological Carcinogenesis with an aim of establishing a new classification scheme based on molecular biological characteristics that would supplement the conventional TNM classification to better predict outcome.Methods: In a literature search involving 822 articles on gastric cancer, eight molecules including p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, matrix metalloproteinase-7 (MMP-7), human epidermal growth factor receptor 2, Regenerating islet-derived family, member 4, olfactomedin-4 and Claudin-18 were selected as candidates to be included in the new molecular classification scheme named G-factor. A total of 210 cases of gastric cancer who underwent curative R0 resection were registered from four independent facilities. Immunohistochemical staining for the aforementioned molecules was performed for the surgically resected specimens of the 210 cases to investigate the correlation between clinicopathological factors and expression of each molecule.Results: No significant correlation was observed between the immunostaining expression of any of the eight factors and postoperative recurrence. However, the expressions of p53 and MMP-7 were significantly correlated with overall survival (OS). When 210 gastric cancer patients were divided into three groups based on the expression of p53 and MMP-7 (G0 group: negative for both p53 and MMP-7, n = 69, G1 group: positive for either p53 or MMP-7, n = 97, G2 group: positive for both of the molecules, n = 44), G2 group demonstrated significantly higher recurrence rate (59 %) compared to 38 % in G0 (p = 0.047). The multivariate regression analysis revealed that G2 group was independently associated with a shorter disease-free survival (DFS) (hazard ratio 1.904, 95 % CI 1.098–3.303; p = 0.022), although the association with OS was not significant. Stage II patients among the G2 group had significantly inferior prognosis both in terms of OS and DFS when compared with those among the G0/G1 group, with survival curves similar to those of Stage III cases.Conclusions: G-factor based on the expression of p53 and MMP-7 was found to be a promising factor to predict outcome of Stage II/III gastric cancer, and possibly to help select the treatment for Stage II cancer, thus supplementing the conventional TNM system.

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