title: Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor.
abstract: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear.
  
  
  
  A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Stage IV cases were selected, and clinical and molecular features were evaluated.
  
  
  
  There was no significant survival difference observed between MSI-H CRC and microsatellite-stable (MSS) CRC in patients with stage IV disease (3.92 vs. 2.50 years; p=0.766). However, hematogenous and lymphogenous metastasis-dominant CRC with MSI-H demonstrated poor prognosis, whereas peritoneal metastasis-dominant CRC with MSI-H demonstrated good prognosis, (1.33 vs. 5.2 years; p=0.006).
  
  
  
  Prognosis of stage IV CRC with MSI-H depended on the metastatic pattern. These findings provide useful information for the adaptation of CRC immunotherapy.
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.|Department of Surgery, Kurume University, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiyoshi
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
authors.forename: Gou
authors.initials: G
authors.lastname: Yamamoto
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takenoya
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kakuta
authors.affiliation: Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Kurume University, Fukuoka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan akagi@cancer-c.pref.saitama.jp.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Akagi
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D009154:Mutation; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000556:secondary; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: C117307:KRAS protein, human; C501486:MLH1 protein, human; D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF mutation; Colorectal cancer; Lynch syndrome; immune-checkpoint inhibitor; microsatellite instability