EFFECT OF CYCLIN D1 AND ASSOCIATED PROTEINS ON PROLIFERATION OF ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

Cyclin D1, which functionally competes with the tumor suppressor genes retinoblastoma (Rb) and p16(INK4), is widely recognized as an oncogen e. p27(KIP1), which inhibits the cyclin D1-CDK4 complex, is also a put ative tumor suppressor gene. In order to evaluate the regulatory inter action of these molecules, a retrospective series of tissues from 66 p atients with esophageal squamous cell carcinoma was evaluated immunohi stochemically for the expressions of cyclin D1, Rb, p16(INK4) and p27( KIP1). Th, expressions of these molecules were correlated with the pro liferation cell nuclear antigen (PCNA) index as an indicator of cell p roliferation. Cyclin D1 was overexpressed (++) in 28 cases (42%), Rb w as lost (-) in 19 cases (24%), p16(INK4) was lost (-) in 37 cases (56% ) and p27(KIPI) was lost (-) in 27 cases (41%). Taken together, disord er of at least one or more of these molecules was observed in 62 cases (92%). Expression of cyclin D1 and p16(INK4) was negatively correlate d (p<0.03), while expression of cyclin D1 and p27(KIPI) was positively correlated (p<0.0004). We found strong overall correlation between ex pression of cyclin D1 and the PCNA index (p<0.0001), however expressio n of p16(INK4) and p27(KIP1) was significantly cell-elated with the PC NA index in tumors devoid of cyclin D1 overexpression (p<0.03 and p<0. 02 respectively). Thus, it was found that cyclin D1 plays a major role and closely related to abnormal cell proliferation in esophageal canc er, however assessment of p16(INK4) and p27(KIP1) status, particularly in tumors devoid of cyclin D1 overexpression, is necessary for compre hensive evaluation of cancer cell proliferation. Furthermore, expressi on of cyclin D1 is correlated with that of p16(INK4) and p27(KIP1) in squamous cell carcinoma of the esophagus.