title: Altered patterns of retinoblastoma gene product expression in adult soft-tissue sarcomas.
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.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Karpeh
authors.forename: M F
authors.initials: MF
authors.lastname: Brennan
authors.forename: W G
authors.initials: WG
authors.lastname: Cance
authors.forename: J M
authors.initials: JM
authors.lastname: Woodruff
authors.forename: D
authors.initials: D
authors.lastname: Pollack
authors.forename: E S
authors.initials: ES
authors.lastname: Casper
authors.forename: M E
authors.initials: ME
authors.lastname: Dudas
authors.forename: E
authors.initials: E
authors.lastname: Latres
authors.forename: M
authors.initials: M
authors.lastname: Drobnjak
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
mesh_terms: D000328:Adult; D005260:Female; D016161:Genes, Retinoblastoma; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000032:analysis*; D012509:Sarcoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000737:chemistry* / Q000401:mortality; D015996:Survival Rate
chemical_list: D016160:Retinoblastoma Protein