C-MYC ONCOGENE AMPLIFICATION AND CYTOMETRIC DNA-PLOIDY PATTERN AS PROGNOSTIC FACTORS IN MUSCULOSKELETAL NEOPLASMS

The relationship between c-myc oncogene amplification in neoplastic ce lls as determined by means of Southern-blot analysis, and their nuclea r DNA content as assessed by combined flow and image cytometry, was in vestigated in fresh tumor specimens from 33 patients with musculoskele tal neoplasms. Amplification, without rearrangement of the c-myc proto -oncogene, was detected in 4 out of 7 bone sarcomas and in 6 out of 26 soft-tissue sarcomas, but in none of 3 benign giant-cell bone tumors. Among the 10 cases with c-myc amplification, 2 were found to be cytom etrically DNA diploid, 2 DNA tetraploid, and 6 DNA aneuploid. Converse ly, there were 10 tumors displaying extremely aneuploid DNA patterns w ithout c-myc oncogene amplification. Thus, there was no relationship b etween c-myc amplification and DNA ploidy; neither did the percentage of S-phase cells, as determined by means of image cytometry, correlate significantly with the occurrence of c-myc amplification. A surprisin g sex-bias was observed; all 6 cases of c-myc-amplified soft-tissue sa rcomas occurred in females, whereas none of the 11 males with such sar comas showed this amplification. When the clinical follow-up data of t he patients were scrutinized, it was found that the DNA ploidy pattern of the neoplastic cell nuclei, in combination with the S-phase values , as well as the occurrence of c-myc amplification, yielded prognostic information, being statistically significant 2 years after the diagno sis. (C) 1994 Wiley-Liss, Inc.