Hodgkin lymphoma comprises two distinct entities; namely nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma. Classical Hodgkin lymphoma is a lymphoid neoplasm composed of monoclonal Hodgkin cells and multinucleated Reed-Sternberg (HRS) cells residing in an infiltrate containing a variable mixture of non-neoplastic small lymphocytes, eosinophils, neutrophils, histiocytes, plasma cells, fibroblasts and collagen fibres. [1
] There are four morphological variants of classical Hodgkin lymphoma, namely nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted. HRS cells are currently thought to be derived from mature B cells at the germinal stage of differentiation, and are pathognomonic in Hodgkin lymphoma. [1
] However, HRS cells may often be scanty and difficult to identify in sections. The pathogenesis of classical Hodgkin lymphoma remains unknown.
ID proteins are key regulators in several developmental and cellular processes. In general, aberrant ID expression seems to favor proliferation, to inhibit differentiation, and to facilitate tumor neoangiogenesis.[2
] From early B-cell development to mature B cells, E2A is the first one of the three transcription factors (E2A, EBF, and PAX5) to be expressed, and E2A together with EBF regulates the expression of PAX5.[3
] The inhibitor of DNA binding ID2 (inhibitor of DNA binding 2 or inhibitor of differentiation, ID2), may bind and negatively regulate E2A and PAX5[5
] by direct interaction. ID2 expression in developing hematopoietic cells seems to repress B-cell development and B-cell-specific gene expression and to favor development of other lineages, [7
] whereas in mature B cells, ID2 is up-regulated during plasma cell differentiation with concomitant loss of expression of several B-cell genes.[12
] Furthermore, the balance between ID2 and E2A, and between ID2 and PAX5 seem to be important for B-cell differentiation.[13
] ID2 has been found strongly and uniformly expressed in the HRS cells of classic Hodgkin Lymphoma and probably represses B-cell-specific gene expression by inactivation of E2A (and perhaps also PAX5). [14
] Expression of two other members of the ID (inhibitor of differentiation) family of proteins, ID1 and ID3, was found to be induced in the presence of latent membrane protein 1 (LMP1), the Epstein-Barr virus oncoprotein, by the activation of NF-kappaB, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling[15
]. However, there is to date no study on the relationship between ID2 and EBV-LMP1 in Hodgkin lymphoma. Overexpression of P16(INK4A)[17
] has been used as a diagnostic adjunct in premalignant and malignant humanpapilloma virus (HPV) lesions in gynecologic pathology[17
] in recent years. Previous research [18
] also suggested that EBV-LMP1 and P16(INK4A) had a role in the carcinogenesis of classical Hodgkin lymphoma, but there was no corresponding investigation of associations between ID2, EBV-LMP1 and p16(INK4A), which might provide further understanding of the mechanism. Therefore, additional studies are needed to identify whether ID2, EBV-LMP1 and P16(INK4A) have similar diagnostic value and to explore the possible relationship between them in classical Hodgkin lymphoma. We used the ID2, EBV-LMP1 and P16(INK4A) antibodies to investigate the possible role of the expression of the three proteins in 60 cases of Chinese classical Hodgkin lymphoma. It is hoped that the study will give information on the pathogenesis of this disease.