title: Loss of Fhit expression is associated with poorer survival in gastric cancer but is not an independent prognostic marker.
abstract: Several studies have reported conflicting results regarding correlations of the loss of Fhit expression with clinicopathological parameters in gastric cancer. We investigated the immunohistochemical expression of Fhit in 362 cases of sporadic advanced gastric adenocarcinoma. The series included 64 cases with microsatellite instability associated with defective mismatch repair genes. Fhit expression resulted absent in 72% of the tumors analyzed. Absence of Fhit expression was more frequent in cases with diffuse and mixed histotype compared to the intestinal histotype (P=0.009). Absence of Fhit expression also correlated with tumor stage (P<0.001), lymph node involvement (P<0.001), presence of distant metastasis (P=0.033), and increasing histological grade (P=0.005). Retained Fhit expression also correlated with microsatellite instability as 61% of instable tumors had lost Fhit expression compared to 74% of microsatellite stable cancers (P=0.050). While loss of Fhit correlates with poorer survival in univariate analysis, it is not an independent prognostic factor in multivariate analysis and is thus not of clinical utility.
authors.affiliation: Dipartimento di Patologia, Sezione Anatomia Patologica, Università di Verona, Strada Le Grazie, 8, 37134, Verona, Italy, p.moore@univr.it.
authors.forename: Emma
authors.initials: E
authors.lastname: Bragantini
authors.forename: Stefano
authors.initials: S
authors.lastname: Barbi
authors.forename: Stefania
authors.initials: S
authors.lastname: Beghelli
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Moore
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Manzoni
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
authors.forename: Anna
authors.initials: A
authors.lastname: Tomezzoli
authors.forename: Carla
authors.initials: C
authors.lastname: Vindigni
authors.forename: Raffaele
authors.initials: R
authors.lastname: Baffa
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000032:analysis* / Q000276:immunology; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy / Q000453:epidemiology; D008207:Lymphatic Metastasis; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase