DISTINCT NONRANDOM PATTERNS OF CHROMOSOMAL-ABERRATIONS IN THE PROGRESSION OF SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECK

Fifty-one randomly selected primary squamous cell carcinomas of the he ad and neck, derived from the larynx (n = 18) and pharynx (oropharynx, n = 18, and hypopharynx, n = 15) were analyzed with centromeric probe s for chromosomes 1, 7, 9, 11, 17, and 18 to study numerical aberratio ns, chromosome imbalances, and aneuploidy by fluorescence in situ hybr idization. The tumors were grouped into nomnetastasizing (N-0) tumors (from patients clinically free of lymph node metastases for at least 1 8 months after surgery, n = 25) and metastasizing (N-1-3) tumors (n = 26). We found a significant association between the tumor ploidy and t he nodal status; in the N-0 group, diploidy prevailed, and the most co mmon aberration was loss to monosomy for chromosome 9 (44%), whereas i n the N-1-3 group, aneuploidy predominated (P = 0.002). Specifically, these genomic changes associated with progression to metastasis were: (a) tetrasomic or polysomic chromosomes were detected in 17 of 26 N-1- 3 tumors but in none of the 25 N-0 tumors (P < 0.0001); (b) heterogene ous chromosomal copy numbers (i.e., extensive chromosomal imbalances) were also much more frequent in the N-1-3 tumors (69.2% versus 24.0%, in the N-0 group; P = 0.018); and (c) loss of chromosome 9 (73%) and g ains of chromosomes 7 (35%) and 17 (31%) persisted, but in addition, l oss of chromosome 18 occurred in 31%. Overexpression of the p53 protei n correlated with an increased incidence of chromosomal imbalances and aneuploidy (P < 0.001) and, hence, constituted an additional risk fac tor. The lower metastatic potential of larynx tumors as compared with tumors from the pharynx was reflected by a lower incidence of these ge nomic changes. These specific patterns of chromosomal aberrations can characterize and distinguish different stages of tumor progression of squamous cell carcinomas of the head and neck and should be valuable d iagnostic and prognostic markers.