Characterization of molecular abnormalities in human fibroblastic neoplasms: A model for genotype-phenotype association in soft tissue tumors

Desmoid tumors and fibrosarcomas (FS) are part of a wide spectrum of disord ered fibroblastic growth that display striking clinical and phenotypic diff erences. This study was designed to characterize molecular abnormalities th at are associated with these differences and to determine their clinical re levance. A cohort of 24 desmoid tumors and 25 low-grade (LG) and 14 high-gr ade (HG) FS that were clinically and pathologically well characterized was analyzed for alterations in expression of Ki-67, Bcl-2, retinoblastoma gene product (pRB), and p,53 by immunohistochemistry, LG-FS and HG-PS showed ab normal expression of Ki-67 (32 versus 86%), Bcl-2 (48 versus 57%), and pRB (56 versus 93%), In contrast, desmoid tumors showed a normal phenotype with these markers. pj3 overexpression was identified in 20% of LG-FS and in 29 % of HG-FS cases hut only in 4% of desmoid tumors. There was an increasing trend in the proportion of abnormal expression of Ki-67, Bcl-2, pRB, and p5 3 with the increase of tumor aggressiveness from desmoid tumors to LG-FS to HG-FS, The molecular differences between tumor entities were highly statis tically significant (P < 0.01), Significant associations between abnormal e xpression of pRB and recurrence-free survival of LG-FS patients (P = 0.05) and between Ki-67 overexpression and recurrence-free survival for tumors of 25 cm were observed (P = 0.02), The demonstrated differences of molecular alterations in HG-FS, LG-FS, and desmoids appear to be related to biologica l aggressiveness of such tumors, and they might be useful to differentiate between histologically similar cases of desmoid tumors and LG-FS, pRB and K i-67 status may be useful to predict recurrence in certain subsets of patie nts.