Differential expression of the suppressor PML and Ki-67 identifies three subtypes of human nasopharyngeal carcinoma.

The promyelocytic leukaemia (PML) gene, which encodes a transformation and growth suppressor, was found to regulate transcription and apoptosis. PML was first identified at the chromosomal translocation break-points t(15;17) of acute promyelocytic leukaemia and the gene product may mediate cell-cycle control and apoptosis. PML was found to interact with the co-transactivator CREB binding protein (CBP) and the apoptotic-modulator Bax. To determine if PML, CBP and Bax may be involved in solid tumours, such as the nasopharyngeal carcinoma (NPC), a rare neoplasia that is prevalent in Southern China, the expression of these proteins and the proliferation marker Ki-67 was analysed by immunohistochemical staining. Expression of PML in the PML-oncogenic domain (POD) or nuclear bodies in most NPC was inversely correlated with the expression of Ki-67. In addition, based on PML expression patterns in NPC three subtypes could be identified, namely, Subtype-1, with strong PML expression in POD structures and with low Ki-67 staining; Subtype-2, where PML was expressed in a homogeneously diffused pattern, but with a low intensity in the tumour cells; while Ki-67 was expressed in a moderate number of cells and Subtype-3, where the majority of tumour cells were PML-negative, while a considerable number of tumour cells were strongly labelled with Ki-67. Furthermore, CBP was present in most of the NPC cells with moderate-strong nuclear staining, while the expression in non-tumour cells were relatively weak. However, there was no direct correlation between PML and CBP expression in the NPC examined. In addition, there was low or no expression of Bax in the NP and NPC. This is, to our knowledge, the first report describing PML and CBP expression in NPC and our data strongly suggests that PML and CBP, but not Bax, may play a role in the transformed phenotypes of NPC.