p16(INK4A) is regularly expressed in Hodgkin's disease: Comparison with retinoblastoma, p53 and MDM2 protein status, and the presence of Epstein-Barrvirus

In order to understand better the possible role of cell-cycle regulating mo lecules in the pathogenesis of Hodgkin's disease (HD), the immunohistochemi cal distribution pattern of p16(INK4A) was investigated and compared with p Rb, p53, and MDM2 protein status in 44 HD cases. Our findings were correlat ed to the presence of Epstein-Barr virus as detected by RNA in situ hybridi zation and clinicopathological parameters. p16(INK4A) protein immunoreactiv ity was found in all 44 cases with a proportion of Hodgkin-Reed-Sternberg ( HRS) cells ranging from 30 to 90%. In 93% of the cases studied, pRb was det ected in HRS, whereas all cases showed overexpression of p53. Almost all sp ecimens (98%) were MDM2-positive as evaluated by 1B10 and/or IF2 monoclonal antibodies. EBER 1/2-transcripts were detected in 31.8% (14 of 44) of the examined samples. A significant correlation was observed between immunoreac tivity of wp16(INK4A) and MDM2 and the number of HRS cells (P =.0012 and P =.018, respectively). In a subgroup of cases, with p16(INK4A) expression in more than 50% of HRS cells, the percentage of pRb-positive neoplastic cell s was inversely related to that of pie-positive ones (P =.007). No clinicop athological parameters or clinical prognostic indicators, including duratio n of response to therapy, were statistically related to the expression leve ls of any of the four proteins investigated or the presence of Epstein-Barr virus. Our findings suggest that p16 and pRb are regularly expressed and t hat their pathway in cell-cycle machinery seems to be intact hp HD. However , further investigation is needed to shed light on the involvement of cell- cycle molecules hp Hodgkin's lymphomagenesis and longer patient follow-up i s required for conclusive prognostic correlation.