Abstract
Altered expression of the retinoblastoma (RB) tumour-suppressor gene product (pRB) has been detected in sporadic bone and soft-tissue sarcomas. Earlier studies, analysing small cohorts of sarcoma patients, have suggested that these alterations are more commonly associated with high-grade tumours, metastatic lesions and poorer survival. This study was designed to re-examine the prevalence and clinical significance of altered pRB expression in a large and selected group of soft-tissue sarcomas from 174 adult patients. Representative tissue sections from these sarcomas were analysed by immunohistochemistry using a well-characterised anti-pRB monoclonal antibody. Tumours were considered to have a positive pRB phenotype only when pure nuclear staining was demonstrated, and cases were segregated into one of three groups. Group 1 (n = 36) were patients whose tumours have minimal or undetectable pRB nuclear staining (< 20% of tumour cells) and were considered pRB negative. Patients with tumours staining in a heterogeneous pattern (20-79% of tumour cells) were classified as group 2 (n = 99). The staining of group 3 (n = 39) was strongly positive with a homogeneous pRB nuclear immunoreactivity (80-100% of tumour cells). pRB alterations were frequently observed in both low- and high-grade lesions. Altered pRB expression did not correlate with known predictors of survival and was not itself an independent predictor of outcome in the long-term follow-up. These findings support earlier observations that alterations of pRB expression are common events in soft-tissue sarcomas; nevertheless, long-term follow-up results indicate that altered patterns of pRB expression do not influence clinical outcome of patients affected with soft-tissue sarcomas. It is postulated that RB alterations are primary events in human sarcomas and may be involved in tumorigenesis or early phases of tumour progression in these neoplasias.
Highlights
We previously studied a group of 44 primary high-grade bone and soft-tissue sarcomas of all age groups using immunohistochemistry, and observed a 70% incidence of altered pRB expression (Cance et al, 1990)
Nuclear staining for pRB was typically observed in endothelial cells, lymphocytes and fibroblasts
We considered tumour samples studied to have a positive pRB phenotype only when pure nuclear staining was demonstrated
Summary
The tumour samples used in this study were obtained fresh following surgical resection, embedded in a cryopreservative solution (OCT compound, Miles, Elkhart, IN, USA), and stored at - 70C until needed. One pathologist (JMW) rereviewed the histopathological diagnosis, tumour grade and quality of the tissue of 280 sarcomas. Bone and tumours of uncertain histopathology were excluded. A total of 174 tumours met the inclusion criteria and were used for analysis. Fisher's exact test was used to assess the association between clinicopathological factors and altered patterns of pRB (Mehta and Patel, 1983). RB expression in adult soft-tIssue sarcomas MS Karpeh et al and Meier, 1958) was used to estimate the survival functions. All non-tumour-related deaths were censored in the Kaplan-Meier analysis. The log-rank test (Peto et al, 1977) was used to compare differences in survival between groups of patients
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call