title: Microsatellite instability as biomarker for risk of multiple primary malignancies of the upper aerodigestive tract.
abstract: Head and neck cancer (HNC) patients are at high risk of developing second primary tumors of the upper aerodigestive tract and this is a chief cause of death. Genomic instability reflecting the propensity and the susceptibility of the genome to acquire multiple alterations is considered a driving force behind multiple carcinogenesis and the alterations of the length of single repetitive genomic sequences or microsatellite instability (MI), implicating impaired DNA repair mechanisms, and could be a sensitive marker for assessing genomic instability in multiple HNC. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes a risk factor in patients with multiple head and neck cancer, we examined replication errors (RER) at 10 microsatellite loci in 21 primary and 5 second primary cancers in 21 patients with multiple malignancies of the upper aerodigestive tract, in comparison with match-paired primary HNC from patients without multiple malignancies. A RER+ phenotype (alterations at > or =2 loci) was observed at 10 microsatellite alterations on chromosomes 2, 3, 11, 17 in at least one tumor from 15 out of 21 (71.5%) patients with multiple primary cancers but only in 11 tumors from 40 (27.5%) HNC patients with single cancer (P=0.001). A RER+ phenotype was also associated with a positive familial cancer history (P=0.046). Our results suggest that a genetic instability may play an important role in the pathogenesis of multiple primary cancers and that testing for MI in a primary HNC may be useful in detecting patients with high risk for developing multiple malignancies of the upper aerodigestive tract.
authors.affiliation: Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Sardi
authors.forename: A
authors.initials: A
authors.lastname: Franchi
authors.forename: C
authors.initials: C
authors.lastname: Bocciolini
authors.forename: C
authors.initials: C
authors.lastname: Mechi
authors.forename: A
authors.initials: A
authors.lastname: Frittelli
authors.forename: L
authors.initials: L
authors.lastname: Bruschini
authors.forename: O
authors.initials: O
authors.lastname: Gallo
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D004261:DNA Replication; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D010610:Pharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D012142:Respiratory Tract Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D012307:Risk Factors; D012907:Smoking
chemical_list: D014408:Biomarkers, Tumor