Possible immortalization of Hodgkin and Reed-Sternberg cells: Telomerase expression, lengthening of telomere, and inhibition of apoptosis by NF-KappaB expression

Telomerase, an enzyme associated with cellular immortality. is expressed on malignant rumor cells. Deregulation of telomerase is thought to facilitate tumorigenesis and cellular immortality by providing cancer cells with unli mited proliferation capacity. Hodgkin and Reed-Sternberg (H&RS) cells are g enerally considered as neoplastic cells in Hodgkin`s disease (HD), however, such cells are only found in a minority of HD lesions. In addition, H&RS c ells with mitotic features are rare and mummified forms are occasionally en countered. There are no available data on the relationship between telomera se activity acid apoptosis in HD. We studied 14 cases with Hodgkin's diseas e (mixed cellularity type, nine cases: nodular sclerosis type. five cases) to clarify the relationship between telomerase activity and apoptosis using in situ hybridization of human telomerase reverse transcriptase (hTERT). r everse transcriptase-polymerase chain reaction (RT-PCR) of hTERT. using ext racted RNA and immunohistochemistry of nuclear factor-kappaB (NF-kappaB), a nd TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) technique for ap optosis. We also analyzed the telomere length, using sorted H&RS cells. TUN EL showed a few apoptotic H&RS cells. but the cells frequently expressed hT ERT. as confirmed by ISH and RT-PCR. Lengthening of the telomere of H&RS ce lls was noted in ten cases. In addition, H&RS cells frequently expressed NF -kappaB, which is known as an inducible transcription factor and inhibitor of apoptosis. Our findings of telomerase activity in H&RS cells indicate th at these cells are neoplastic acid are potentially immortal. In addition, N F-kappaB expression on H&RS cells suggests its possibility in inhibition of apoptosis of these cells.