Prognostic And Predictive Value Of c-erbB2 Overexpression In Osteogenic Sarcoma

摘要

Introduction: Osteogenic sarcoma is a highly malignant tumor of the bone, seen between 10-30 years of age. The over expression of c-erbB-2 proto-oncogene has been correlated with early metastasis and poor survival rate in various human tumors. There are very few reports in the literature regarding determination of c-erb B-2 (HER-2eu) expression in cases of osteogenic sarcomas and also the results in these reports are quite variable. The aim was to study the expression of c-erbB-2 and its correlation with the survival rate in patients of osteogenic sarcoma. Materials and Methods: A retrospective study (1997-2003) of a total of 20 cases of osteogenic sarcoma. Monoclonal antibody against c-erbB-2/HER- 2/Neu Ab-12 (clone CB 11) was used and expression of c-erbB-2 in these 20 cases of osteogenic sarcoma was studied and correlated with the disease free survival time of patients. Results: 3 cases showed no staining positivity, 1+ was seen in 5 cases. 3 cases showed 2+ and 3 cases had 3+ positivity. 4+ cytoplasmic positivity was noted in 6 cases. The intensity of cytoplasmic staining of c-erbB-2 did not correlate with survival rate of the patients, response to chemotherapy and metastasis. Conclusion: c-erbB-2/HER-2 has been considered as an independent prognostic factor in osteogenic sarcoma, but in the present study, the expression was not seen to be correlating with survival rate of the patients. Therefore, further studies are needed to reach a consensus regarding the reliability of c-erbB-2 as an independent prognostic factor in osteogenic sarcoma. Introduction Osteogenic sarcoma is the most frequent and highly malignant bone tumor, seen during second and third decade of life1. Several oncogenes and tumor suppressor genes are reported to be involved in the oncogenesis of osteogenic sarcoma. Although survival rate increased up to 60-70% within the last 20 years, the problem of non-response to chemotherapy remains. There are many factors thought to have an influence on prognosis of osteosarcoma, but their exact role is still controversial. The overexpression of c-erbB-2 (also called neu or HER2) proto-oncogene has been studied and correlated with poor survival rate in various human tumors especially breast carcinomas. Little is known about the expression of c-erbB-2 in sarcomas2, especially osteogenic sarcoma and only few reports are available in the literature, that to showing controversial results. Therefore, in the present study, we studied 20 cases of osteogenic sarcoma for expression of c-erbB-2 (HER-2eu) and correlated the expression with the survival rate of patients. Materials and Methods The present study is a retrospective study (1997-2003) in the Department of histopathology. A total of 49 cases of osteogenic sarcoma were retrieved from surgical pathology files. Clinical details of cases were reviewed for age, sex, clinical presentation & diagnosis, pathological diagnosis and treatment. Out of these 49 cases, proper follow up data was available in only 20 cases. The follow up data was collected from the radiotherapy files of these cases and their total as well as disease free survival was noted. Histological sections were obtained from formalin fixed paraffin embedded tissues. The sections were restained in these cases and all cases were reviewed by the pathologist to confirm the diagnosis of osteogenic sarcoma. For immunohistochemistry, a representative blocks with adequate viable tumor (avoiding areas of necrosis) were chosen. Monoclonal antibody against c-erbB-2/HER- 2/Neu Ab-12 (clone CB 11) was obtained from Neomarkers. 3-4 μm thick sections were cut from tissue blocks, placed on pretreated glass slides, dried at 37°C overnight and then at 60°C for 30 minutes. Sections were dewaxed and rehydrated through graded alcohols. Inhibition of endogenous peroxidase was done by treatment for 30 minutes with 3% hydrogen peroxide in methanol. After washing, blocking was done with normal serum and 4 rinses with buffer were giv