Sarcomatoid carcinoma of the head and neck: molecular evidence for evolution and progression from conventional...

The underlying events associated with the development of sarcomatoid head and neck squamous carcinoma and the biologic significance remain unknown. To investigate the genetic events involved in the evolution of this entity, comparative analysis of matched microdissected epithelial and sarcoma-like components from 11 primary sarcomatoid carcinomas was performed using microsatellite markers. Nine markers on chromosomes 4p, 9p, and 17p regions (3 per each chromosomal region) were selected based on their informativeness, small product size, and the high alterations in head and neck squamous carcinomas. In this study, loss of heterozygosity (LOH) in at least one marker in either component was noted in all 11 tumors, and instability was found in 10 instances (six in 3 paired specimens and four in the sarcomatoid area only). Concordant results in both components were found in 58 (79.5%) reactions (37 LOH and 21 retention of heterozygosity), and paradoxical findings were noted in 15 instances (20.5%). The latter included LOHs in only two conventional epithelial components and 13 sarcomatoid components. Both keratin-positive and -negative sarcomatoid tumors had a comparable frequency of LOH. The most frequently altered markers in both components were D9S168 and D9S171 (75% each) and D4S1587 (66%). The sarcomatoid components manifested distinctly high alterations at marker D17S520 on chromosome 17p. Our study supports: 1) an evolution of sarcomatoid carcinoma from the conventional epithelial-type, 2) a malignant nature of the sarcomatoid component, and 3) that molecular progression is associated with the sarcomatoid transformation.