title: Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer.
abstract: BACKGROUND
  The clinical role of microsatellite instability (MSI) in gastric cancer (GC) is controversial. A large series of patients submitted to respective surgery for primary GC with a long follow-up time was evaluated.
  
  
  METHODS
  472 patients with prospectively collected frozen samples of normal mucosa and tumor tissue stored in a biological tissue bank were included. Microsatellite analysis was evaluated using 5 quasi monomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21, and NR-27). The presence of MSI in 2 or more loci was classified as MSI-H, whereas all other cases were included in the microsatellite-stable (MSS) group.
  
  
  RESULTS
  MSI-H phenotype was found in 111 of 472 patients (23.5%). MSI-H status was related significantly with older age, female gender, non-cardia location, WHO histotype, non-cardia Lauren intestinal type, and less advanced stages. Cancer-related 5-year survival was significantly higher in MSI-H versus MSS group (67.6% vs. 35%, p < 0.001). Stratified analysis revealed a significant impact of MSI on prognosis in non-cardia tumors of intestinal type or tubular/poorly differentiated histology, particularly in stages II and III; multivariate Cox regression analysis confirmed MSS status as a strong predictor of poor prognosis (hazard ratio 2.65, 95% CI 1.56-4.51, p < 0.001) in non-cardia intestinal type. No prognostic value of MSI in the diffuse-mixed type and signet-ring cell/mucinous histotypes was observed.
  
  
  CONCLUSIONS
  MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Marrelli
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy. polom.karol@gmail.com.
authors.forename: Karol
authors.initials: K
authors.lastname: Polom
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pascale
authors.affiliation: Department of Pathology, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Vindigni
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Piagnerelli
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: De Franco
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Department of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Garosi
authors.affiliation: Department of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Petrioli
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Unit of Surgical Oncology, University of Siena, Siena, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D002299:Cardia / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate