LOSS OF 18Q AND HOMOZYGOSITY FOR THE DCC LOCUS - POSSIBLE MARKERS FORCLINICALLY AGGRESSIVE SQUAMOUS-CELL CARCINOMA

Karyotyping and polymorphisms within the DCC (deleted in colon cancer) locus (18q21) were used to analyze loss of chromosome 18 in squamous cell carcinomas (SCC). Tumors from 26 patients (including 7 for whom m atched tumor and normal DNA samples were available) were examined for heterozygosity within DCC. Of the seven normal-tumor combinations, fou r were informative. Two of these had loss of heterozygosity (LOH) at D CC. For 19 SCC tumor cultures normal tissue was not available. These w ere scored only as homozygous or heterozygous. The majority were homoz ygous. Only 3/19 (15%) were heterozygous. In contrast, in a panel of n ormal blood samples the majority, 11/16 (69%), were heterozygous. Alle lic zygosity was concordant with the chromosome 18 content in the 16 a rmors that were also karyotyped. Tumors fr om 40 patients 37 that were karyotyped and three that were informative at the DCC locus, were ass essed for loss of chromosome 18 and patient survival. Loss of part or all of chromosome 18 occurred in tumors from 25. Twenty-seven of the 4 0 patients have died and 13 are alive. There was strong association be tween loss of 18 and overall survival. Of those who are alive only 5/1 3 (38%) had loss of 18, whereas among those who have died 20/27 (74%) had loss of 18. By chi(2) analysis the association of loss of 18 and d eath from cancer was significant (p>0.01). The high frequency of chrom osome 18 loss in SCC suggests that this region contains one or more tu mor suppressor genes important in the clinical behavior of SCC. DCC is one candidate, brit other regions of loss not including the DCC locus indicate that chromosome 18 probably contains more than one tumor sup pressor locus. Prospective studies of chromosome 18 loss as a single p rognostic indicator are strongly indicated in this tumor type since lo ss in early stage armors might indicate a need for more aggressive the rapy than would be given on the basis of staging alone.