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Rb Loss and KRAS Mutation Are Predictors of the Response to Platinum-Based Chemotherapy in Pancreatic Neuroendocrine Neoplasm with Grade 3: A Japanese Multicenter Pancreatic NEN-G3 Study.
Hijioka, Susumu; Hosoda, Waki; Matsuo, Keitaro; Ueno, Makoto; Furukawa, Masayuki; Yoshitomi, Hideyuki; Kobayashi, Noritoshi; Ikeda, Masafumi; Ito, Tetsuhide; Nakamori, Shoji; Ishii, Hiroshi; Kodama, Yuzo; Morizane, Chigusa; Okusaka, Takuji; Yanagimoto, Hiroaki; Notohara, Kenji; Taguchi, Hiroki; Kitano, Masayuki; Yane, Kei; Maguchi, Hiroyuki; Tsuchiya, Yoshiaki; Komoto, Izumi; Tanaka, Hiroki; Tsuji, Akihito; Hashigo, Syunpei; Kawaguchi, Yoshiaki; Mine, Tetsuya; Kanno, Atsushi; Murohisa, Go; Miyabe, Katsuyuki; Takagi, Tadayuki; Matayoshi, Nobutaka; Yoshida, Tsukasa; Hara, Kazuo; Imamura, Masayuki; Furuse, Junji; Yatabe, Yasushi; Mizuno, Nobumasa.
Afiliação
  • Hijioka S; Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. rizasusu@aichi-cc.jp.
  • Hosoda W; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Matsuo K; Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
  • Ueno M; Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan.
  • Furukawa M; Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, Japan.
  • Yoshitomi H; Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Kobayashi N; Department of Oncology, Yokohama City University Hospital, Yokohama, Japan.
  • Ikeda M; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • Ito T; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Nakamori S; Department of Hepato-Biliary-Pancreatic Surgery, Osaka National Hospital, Osaka, Japan.
  • Ishii H; Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Kodama Y; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto.
  • Morizane C; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
  • Okusaka T; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
  • Yanagimoto H; Department of Surgery, Kansai Medical University, Hirakata, Japan.
  • Notohara K; Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan.
  • Taguchi H; Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
  • Kitano M; Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Sayama, Japan.
  • Yane K; Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.
  • Maguchi H; Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.
  • Tsuchiya Y; Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
  • Komoto I; Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan.
  • Tanaka H; Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan.
  • Tsuji A; Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
  • Hashigo S; Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Kawaguchi Y; Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan.
  • Mine T; Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan.
  • Kanno A; Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Murohisa G; Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
  • Miyabe K; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Takagi T; Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
  • Matayoshi N; Department of Surgery I, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
  • Yoshida T; Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Hara K; Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Imamura M; Department of Neuroendocrine Tumor Center, Kansai Electric Power Hospital, Osaka, Japan.
  • Furuse J; Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.
  • Yatabe Y; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Mizuno N; Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
Clin Cancer Res ; 23(16): 4625-4632, 2017 Aug 15.
Article em En | MEDLINE | ID: mdl-28455360
Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival.Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed.Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035).Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625-32. ©2017 AACR.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Protocolos de Quimioterapia Combinada Antineoplásica / Proteínas Proto-Oncogênicas p21(ras) / Proteína do Retinoblastoma / Tumores Neuroendócrinos / Mutação Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Protocolos de Quimioterapia Combinada Antineoplásica / Proteínas Proto-Oncogênicas p21(ras) / Proteína do Retinoblastoma / Tumores Neuroendócrinos / Mutação Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Asia Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão