Patterns of chromosomal aberrations in metastasizing and nonmetastasizing squamous cell carcinomas of the oropharynx and hypopharynx

Although several cytogenetic events of the tumor progression cascade have b een identified in the past, the specific types of chromosomal alterations t hat lead to the development of lymph node metastases are still unknown. Ope rative specimens of 20 patients (10 patients with metastasizing tumors, 10 patients with nonmetastasizing tumors) with squamous cell carcinomas of the oropharynx and hypopharynx, along with the corresponding lymph node metast ases, were investigated by quantitative DNA measurements and comparative ge nomic hybridization (CGH). Nonmetastasizing tumors (NO) displayed overrepre sentations on chromosomes 10q (8 cases); 5p (7 cases); 3q and 20q (6 cases each); 8q (5 cases); 1p and 21q (4 cases each); 7p and 20p (3 cases each); and 2p, 15q, and 19q (2 cases each). Loss of chromosomal material was found on 5q, 9p, and 14q (2 cases each). Metastasizing tumors (N+) demonstrated overrepresentations on chromosomes 5p, 15q, and 22q (6 cases each); 3q and 11q13 (5 cases each); 20p and 21q (4 cases each); and 10q (3 cases). In 2 c ases, an overrepresentation of the chromosomal arm 3q was accompanied by a loss of chromosomal arm 3p. Less frequent overrepresentations were observed on chromosomes 1q and 17q. Deletions were found on chromosomes 18q (3 case s), 3p, 4q, 5q, and 19p (2 cases each); and sporadic deletions occurred on 2q, 6q, 8p, 9p, 10p, 13q, 14q, 15q, and 16q. Whereas overrepresentations on chromosomes Ip and 7p occurred exclusively in NO tumors, overrepresentatio ns on chromosomes 1q, 11q, and 22q, along with deletions on 18q, were only observed in N+ tumors. Quantitative DNA measurements revealed a significant ly higher percentage of aneuploid cells and a higher degree of DNA entropy in the N+ tumors. Chromosomal overrepresentations on chromosomes 1q, 8q, 11 q, 18q, and 19q occurred more frequently in the metastases than in the corr esponding primary tumors. Pairwise analysis of chromosomal alterations in t he primary tumors and associated lymph node metastases revealed a genetic r elationship, although a greater number of chromosomes on average were affec ted in the lymph node metastases. Quantitative DNA measurements demonstrate d greater aneuploid values in the metastases. Recurring patterns of chromos omal alterations in NO and N+ tumors were demonstrated in this study. In ge neral, metastasizing tumors are characterized by overrepresentations on chr omosomes 11q13 and 22q, and deletions on 18q. These aberrations suggest an elevation along the tumor progression cascade.