ALTERED PATTERNS OF RETINOBLASTOMA GENE-PRODUCT EXPRESSION IN ADULT SOFT-TISSUE SARCOMAS

Altered expression of the retinoblastoma (RB) tumour-suppressor gene p roduct (pRB) has been detected in sporadic bone and soft-tissue sarcom as. Earlier studies, analysing small cohorts of sarcoma patients, have suggested that these alterations are more commonly associated with hi gh-grade tumours, metastatic lesions and poorer survival. This study w as designed to re-examine the prevalence and clinical significance of altered pRB expression in a large and selected group of soft-tissue sa rcomas from 174 adult patients. Representative tissue sections from th ese sarcomas were analysed by immunohistochemistry using a well-charac terised anti-pRB monoclonal antibody. Tumours were considered to have a positive pRB phenotype only when pure nuclear staining was demonstra ted, and cases were segregated into one of three groups. Group 1 (n = 36) were patients whose tumours have minimal or undetectable pRB nucle ar staining (<20% of tumour cells) and were considered pRB negative. P atients with rumours staining in a heterogeneous pattern (20-79% of tu mour cells) were classified as group 2 (n = 99). The staining of group 3 (n = 39) was strongly positive with a homogeneous pRB nuclear immun oreactivity (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 express ion 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 RE alterations are primary events in h uman sarcomas and may be involved in tumorigenesis or early phases of tumour progression in these neoplasias.