Characterization of molecular abnormalities in human fibroblastic neoplasms: A model for genotype-phenotype association in soft tissue tumors Journal Article
| Authors: | Hoos, A.; Lewis, J. J.; Antonescu, C. R.; Dudas, M. E.; Leon, L.; Woodruff, J. M.; Brennan, M. F.; Cordon-Cardo, C. |
| Article Title: | Characterization of molecular abnormalities in human fibroblastic neoplasms: A model for genotype-phenotype association in soft tissue tumors |
| Abstract: | Desmoid tumors and fibrosarcomas (FS) are part of a wide spectrum of disordered fibroblastic growth that display striking clinical and phenotypic differences. This study was designed to characterize molecular abnormalities that are associated with these differences and to determine their clinical relevance. A cohort of 24 desmoid tumors and 25 low-grade (LG) and 14 high-grade (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 p53 by immunohistochemistry. LG-FS and HG-FS showed abnormal 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, p53 overexpression was identified in 20% of LG-FS and in 29% of HG-FS cases but only in 4% of desmoid tumors. There was an increasing trend in the proportion of abnormal expression of Ki-67, Bcl-2, pRB, and p53 with the increase of tumor aggressiveness from desmoid tumors to LG-FS to HG-FS. The molecular differences between tumor entities were highly statistically significant (P < 0.01). Significant associations between abnormal expression 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 >5 cm were observed (P = 0.02). The demonstrated differences of molecular alterations in HG-FS, LG-FS, and desmoids appear to be related to biological aggressiveness of such tumors, and they might be useful to differentiate between histologically similar cases of desmoid tumors and LG-FS. pRB and Ki-67 status may be useful to predict recurrence in certain subsets of patients. |
| Keywords: | adolescent; adult; cancer survival; child; controlled study; human tissue; protein expression; school child; aged; aged, 80 and over; disease-free survival; middle aged; cancer recurrence; ki 67 antigen; ki-67 antigen; phenotype; cell cycle; cell division; gene overexpression; protein bcl 2; apoptosis; gene expression; tumor markers, biological; genetic association; genotype; gene product; protein p53; cancer invasion; fibrosarcoma; tumor suppressor protein p53; cancer classification; retinoblastoma protein; soft tissue neoplasms; soft tissue tumor; desmoid tumor; fibromatosis, aggressive; humans; prognosis; human; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 61 |
| Issue: | 7 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2001-04-01 |
| Start Page: | 3171 |
| End Page: | 3175 |
| Language: | English |
| PUBMED: | 11306504 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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