Two distinct regions of loss on chromosome arm 4q in primary head and necksquamous cell carcinoma

Objective: To more clearly define the frequency and the regions of chromoso me arm 4q loss in head and neck squamous cell carcinoma. Design: A retrospective microsatellite analysis of DNA from previously micr odissected primary tumor samples. Setting: Academic medical center. Patients and Methods: One hundred primary tumor samples from patients with head and neck squamous cell carcinoma were analyzed for loss of heterozygos ity on the long arm of chromosome 4. The Kaplan-Meier method was used to es timate survival for 97 patients for whom clinical data were available. The Cox proportional hazards model was used to compare survival, and logistic r egression was used to search for associations between clinical tumor charac teristics and 4q status. Results: Analysis of 33 polymorphic microsatellite markers identified 51 sa mples (51%) exhibiting loss of heterozygosity of 4q in at least 1 locus. Ei ghteen tumors revealed loss at all informative markers, indicating monosomy or complete deletion of 4q. Thirty-three tumors displayed partial loss of heterozygosity and delineated 2 minimal areas of loss at 4q2324 and 4q2829. Eleven rumors displayed loss solely at the 4q2324 region, 13 tumors displa yed deletions confined to the 4q2829 region, and 9 tumors displayed selecti ve loss at both regions. A separate analysis in a subset of 94 primary head and neck tumors was done to further delineate the minimal area of chromoso mal loss at 4q2324. Analysis of 8 markers in this region allowed us to iden tify the smallest region of loss between markers D4S2986 and D4S1564 (a dis tance of 2 centimorgans). Review of the clinical records of 97 patients rev ealed no statistically significant association between 4q status and any cl inical variable, including survival. Conclusion: These results confirm a high frequency of chromosome arm 4q los s in primary head and neck squamous cell carcinoma and might demarcate 2 no vel putative suppressor loci involved in progression of this carcinoma.