Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma

✍ Scribed by Ai-Min Hui; Xin Li; Masatoshi Makuuchi,; Tadatoshi Takayama; Keiichi Kubota

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 352 KB
• Volume: 84
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19991222)84:6<604::aid-ijc11>3.0.co;2-y

✦ Synopsis

To determine the role of retinoblastoma (Rb) gene alteration in hepatocarcinogenesis, we examined Rb protein expression immuno-histochemically in a series of surgically resected specimens including non-cancerous liver tissues with cirrhosis or chronic hepatitis, large regenerative nodules, pre-cancerous adenomatous hyperplasias as well as primary and metastatic lesions of hepatocellular carcinoma (HCC). All of the non-cancerous liver tissues, large regenerative nodules and adenomatous hyperplasias showed normal Rb protein expression. Altered Rb protein expression was observed in 31 (lack of Rb protein in 16 and over-expression in 15) of the 81 primary HCCs (38%) and was significantly associated with tumor differentiation grade: altered Rb protein expression occurred in 1 of 23 (4%), 16 of 43 (37%) and 14 of 15 (93%) well-, moderately and poorly differentiated tumors (moderately vs. well-differentiated p F 0.01; poorly vs. moderately differentiated p F 0.001). Incidences of both Rb protein absence and over-expression were higher for moderately differentiated than for well-differentiated tumors and even higher for poorly differentiated tumors. Rb protein absence and over-expression were observed in 9 (39%) and 10 (44%) of the 23 metastatic lesions of HCC, respectively, and the incidence of altered Rb protein expression (absence or over-expression) was significantly higher than in primary lesions (83% vs. 38%, p F 0.001). Our observations suggest that elevated and absent Rb protein are closely associated with tumor progression and developing metastatic disease rather than tumor initiation in cases of HCC.