The Study On The Clinicopathological Characteristics And Prognostic Factors Of The Malignant Fibrous Histiocytoma

Objectives: The purpose of this study was to assess the clinicopathological characteristics and prognostic factors that could influence management and clinical outcome of Malignant Fibrous Histiocytoma (MFH) of soft tissue, by reviewing the cases and examining the expression of vascular growth factors and invading protein of tumor and its inhibitor at the same time.Methods: According to the new classified criterion of soft tissue tumor, which made by WHO in 2002 .Between January 2000 and January 2007, 126 patients with plemorphic MFH treated by surgery in our institution were reviewed retrospectively. Statistical analysis was carried out using SPSS 13.0. The Kaplan-Meier method was used to estimate clinicopathological features and patients' survival, and differences in the probabilities were evaluated using the log-rank test. Cox's proportional hazards model was performed to identify factors that were independently associated with the prognosis. At the same time, Immunohistochemistry for MMP-2, TIMP-2, VEGF and FGF-2 were performed including 80 cases of MFH. The positive expression rates were investigated and compared with clinicopathological parameters and survival rate.Results: 126 patients were reviewed , 80 men and 46 women. The average age is 53.1 years, which ranged from 3 to 83 years. Tumors were located on trunk in 38 patients (30.2%), the lower extremity in 62 patients (49.2%), and the upper extremity in 26 patients (20.6%). Tumor size ranged from 1.5 cm to 30 cm, less than 5cm in 78 patients (61.9%), more than 5 cm in 48 patients (38.1%). Tumors were located superficial to the investing muscular fascia in 14 patients (11.1%) and deep to or involving it in 112 patients (88.9%). Tumors were staged according to the AJCC Staging System (2002) for STS. The distribution of the 126 patients according to the staging system was as follows: 73 Stage II (58.0%), 44 Stage III (34.9%) and 9 Stage IV(7.1%). There were 16 in marginal resection (12.7%), 70 in tumor wide resection (55.6%), or 40 in tumor bed wide resection (31.7%). 33 patients (26.2%) received postoperative chemotherapy and 93 patients (73.8%) without it. Chemotherapy drugs were traditional drugs, including IFO,VCR,DTIC,THP,CTX et al. 29 patients (23.0%) received postoperative radiation therapy and 93 patients (77%) without it, postoperative radiation at a mean dose of 43 Gy. Local recurrences were observed in 57 patients (45.2%), Local recurrences-free in 69 patients (54.8%). The metastases of lung were detected in 46 patients (36.5%) and multiple metastases were in 6 patients (4.8%). The median follow-up was 74.5 months (range, 1-90 months). The one, three and five year's over-all survival rates of the patients were 77%, 61% and 52%. A total of 52 patients were died. The exploratory analysis was used to identify risk factors (including patient's sex and years, tumor location, size, depth, stage, operation, postoperative chemotherapy, postoperative radiation, local recurrence and metastases) for survival in patients with MFH. Factors On univariate analysis, tumor size, depth, stage, operation modes, postoperative radiation, local recurrence and metastases were found to be correlated with survival rate. On multivariate analysis, tumor stage and metastases were the correlated factors of prognosis.Among 80 MFH patients, all targets were mainly distributed in cytoplasm of cells. Positive expression rates of MMP-2,TIMP-2 were 83.8% and 82.5% respectively, Positive expression rates of VEGF,FGF-2 were all 83.8%.By analyzing all the targets, positive expression rates of MMP-2 were significantly higher and TIMP-2 were significantly lower in metastases patients than in without metastases patients(P=0.001 and P=0.000, respectively). Survival rate was higher in low positive expression rates of MMP-2 than high positive (P=0.000). On the contrary, survival rate was higher in high positive expression rates of TIMP-2 than low positive (P=0.000). The expression of VEGF was correlated with pathology grade and metastases of MFH (P=0.026 and P=0.002, respectively), and had no correlation with other factors. The expression of VEGF in high-grade and metastases was significantly high. The expression of FGF-2 was no correlation with all factors. Survival rate was no difference between high expression and low expression of VEGF (P=0.194), but exploratory analysis of survival curve, long time survival rate was higher in low expression of VEGF than in high expression. There was no difference of survival in expression of FGF-2 groups (P=0.314) . There was negative correlation between MMP-2 and TIMP-2, positive correlation between MMP-2 and VEGF (P=0.004 and P=0.034, respectively) . Conclusions: MFH has become the most common soft tissue sarcoma with incidence of disease in men a little higher than women. Its distinct characters were highly malignant and poor prognosis. On univariate analysis, tumor size, depth, stage, operation modes, postoperative radiation, local recurrence and metastases were found to be correlated with survival rate. On multivariate analysis, tumor stage and metastases were the correlated factors of prognosis.In MFH patients, the correlation between MMP-2 and TIMP-2 is negative, and their abnormal expressions maybe increase metastases and influence prognosis. No correlation between VEGF and FGF-2. Long time survival rate was higher in low expression of VEGF than in high expression. There was positive correlation between MMP-2 and VEGF, during the progress of tumor invading and metastases. They maybe coadjust and stimulate each other to destroy the basic membrane, and to develop the tumor's vascular.