Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma.

PURPOSE: To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS). PATIENTS AND METHODS: VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative. RESULTS: Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1-93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup( P=0.01, by log-rank sum test). CONCLUSION: Twenty-four point nine percent of STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.

HER-2/neu and CD117 (C-kit) overexpression in hepatocellular and pancreatic carcinoma.

BACKGROUND: Hepatocellular carcinoma has an overall 5-year survival of less than 5%. Similarly, pancreatic cancer has a mortality: incidence ratio of 0.99. The aim of this study was to determine the prevalence of HER-2/neu and c-kit (CD117) overexpression and to identify a possible predictive role in patients with these two malignancies. MATERIALS AND METHODS: We performed a retrospective study on archival specimens of subjects with hepatocellular and pancreatic carcinoma. HER-2/neu and CD117 overexpression were evaluated by immunohistochemistry. RESULTS: Thirty-three patients with pancreatic carcinoma and 25 patients with hepatocellular carcinoma were identified. The mean age was 71.7 years for patients with pancreatic carcinoma and 66 years for patients with hepatocellular carcinoma. Two patients with hepatocellular carcinoma and none with pancreatic cancer overexpressed HER-2/neu, while 2 patients with pancreatic carcinoma and 1 patient with hepatocellular carcinoma overexpressed CD117. CONCLUSION: HER-2/neu and CD117 are not significantly overexpressed in either cancer. There appears to be no role for the use of trastuzumab in either malignancy. Similarly, while there appears to be no role for tyrosine kinase inhibitors in the treatment of hepatocellular carcinoma, further larger studies are necessary in pancreatic adenocarcinoma.

Immunohistochemical detection of HER-2/neu, c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas.

PURPOSE: The aim of this study was to determine the incidence of HER-2/neu, VEGF and CD117 overexpression in soft tissue sarcomas (STS) and to study the effect of this overexpression, if present, on survival in patients with specific histological subtypes of STS. MATERIALS AND METHODS: We conducted a retrospective observational study on patients diagnosed with STS during the period of 1986-2001. HER-2/neu overexpression was measured in these patients by immunohistochemistry (IHC) using the Hercep test developed by DAKO. VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). Immunohistochemical staining for c-kit was performed using a 1:250 dilution of the rabbit polyclonal antibody A4502 (IMPATH, CA) with the EnVision detection system. RESULTS: Two hundred and seventy three patients were diagnosed as having STS between 1986 and 2001, however of these patients, only 90 (51 females and 49 males) had enough sample available for testing. Patients who overexpressed VEGF had a significantly shorter survival (23 vs. 52 months; p=0.01). There was no effect of overexpression of either CD117 or HER-2/neu on survival. Studying the individual histological subtypes we found that, in malignant fibrous histiocytoma, overexpression of either VEGF or CD117 increased survival (41.3 vs. 19.5 months, p=0.01; and 84.5 vs. 17 months, p=0.006 respectively). In leiomyosarcoma, VEGF overexpression significantly decreased survival (7.5 vs. 76 months, p=0.03), while CD117 overexpression significantly increased survival (70.9 vs. 46.3 months, p=0.03). CONCLUSION: VEGF overexpression is associated with an adverse outcome in STS. Whether this is true of any particular histological subtype is unclear and needs further investigation. Also, site-specific agents targeting these three bio-markers (alone or with conventional therapy) may have a therapeutic role and need to be elaborated in future clinical trials.