Immunohistochemical Evaluation of MET and RON Expression in Myxofibrosarcomas and the Correlation with Clinicopathological Parameters and Survival
JC Lee, CF Li, HY Huang. National Taiwan University Hospital, Taipei, Taiwan; Chi-Mei FoundationMedical Center, Tainan, Taiwan; Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Background: Myxofibrosarcoma (MFS) relatively lacks good prognosticator. Our unpublished data from array-based comparative genomic hydridization analysis on 12 tumor specimens and 2 cell lines showed frequent gains in chromosomal 7q spanning regions harboring c-MET oncogene. MET expression is known to be associated with invasive growth pattern and drugs targeting it are being developed. RON, a homologue to MET, can elicit reciprocal transphosphorylation with MET. Their expression was found to predict poorer prognosis in various human cancers. Our goal is to detect the expression of these two proteins in MFS and evaluate the prognostication power of them.
Design: We retrospectively collected 73 cases of MFS and performed immunohistochemical stain with MET and RON antibodies. The results were correlated with clinicopathological parameters, which, as well as MET and RON expression, were further correlated with overall survival and metastasis-free survival in 62 patients with available follow-up data.
Results: High MET expression (50 cases, 68.5%) was significantly associated with higher FNCLCC grade, higher AJCC stage, higher mitotic rate, more extensive necrosis, less myxoid area (p<0.001 for all above), larger tumor size (p=0.001), positive margin (p=0.002), and deeper site (p=0.035). High RON expression (36 cases, 49.3%) was significantly associated with higher stage (p=0.005), higher mitotic rate (p=0.012), and less myxoid area (p=0.027). Significant positive correlation between expression of MET and RON was also demonstrated (p<0.001, correlation coefficient=0.451). Univariate analysis revealed that overall survival was significantly correlated with mitoses, margin, depth, and stage, among which only mitoses (p=0.0003, risk ratio [RR]=27.736) were significant in multivariate analysis; metastasis-free survival was significantly correlated with mitoses, grade, MET expression, depth, stage, necrosis, size, margin, and RON expression, among which only the first four were significant in multivariate analysis (p=0.0001, 0.0185, 0.0198, 0.0348, and RR= 57.678, 11.764, 11.582, 28.000, respectively).
Conclusions: Expression of MET, RON or both is common in MFS. While both were insignificant for overall survival, MET expression was predictive of higher rate of metastasis. In addition, mitotic rate was the strongest prognosticator according to this work.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 22, Monday Afternoon