COMMON CLONAL ORIGIN OF SYNCHRONOUS PRIMARY HEAD AND NECK SQUAMOUS-CELL CARCINOMAS - ANALYSIS BY TUMOR KARYOTYPES AND FLUORESCENCE IN-SITU HYBRIDIZATION

Two synchronously arising primary squamous cell carcinomas (SCC) origi nating from separate sites in the anterior floor of mouth (FOM) and th e pyriform sinus (PS) were evaluated by karyotype and fluorescence in situ hybridization (FISH) to determine whether they were of common or independent ancestry. The primary tumors were designated Henry Ford Ho spital (HFH)SCC-8a (FOM) and HFH-SCC-9a (PS), and the respective recur rent tumors after chemotherapy and radiation were designated -8b and - 9b. HFH-SCC-8a and -8b were cultured and had closely related hypotetra ploid karyotypes of monoclonal origin. Karyotypes could not be obtaine d from the second primary tumor HFH-SCC-9a or its recurrence -9b. Howe ver, we used karyotypes from HFH-SCC-8a and -8b as a guide to select F ISH probes for the histological evaluation of genetic markers in tumor sections. Fluorescence in situ hybridization on metaphase chromosomes from the cell cultures was useful in modifying the tumor karyotypes. Fluorescence in situ hybridization identified a chromosome Y rearrange ment that was not obvious from the HFH-SCC-8a and -8b karyotypes, and this Y rearrangement served as a unique clonal marker. Using two probe s for the Y chromosome we showed that all four tumors shared the same Y rearrangement with loss of Yq (DYZ1) and retention of Ycen (DYZ3). F urthermore, FISH showed that all four tumors had the same aneuploidy p atterns for chromosomes X, Y, 7, 9, 15, 16, and 17. From karyotypic an d FISH analysis disomy for X and 9 centromere regions and the rearrang ed Y were all predicted and observed in the tumor tissue sections. Tet rasomy and trisomy for 7, 15, 16, and 17 were predicted from the karyo types and this also was observed using FISH in all four tumors. These FISH aneuploidy patterns and the presence of a clonal Y marker in all four tumor samples indicate that the synchronous primaries and their r ecurrences were of monoclonal origin. Copyright (C) 1995 by W.B. Saund ers Company