Telomerase activity, telomere length, and apoptosis: a comparison between acquired cholesteatoma and squamous cell carcinoma.

Background: Cholesteatoma disease is characterized by accumulation of keratinizing epithelium. Several molecular markers of tumor formation have been found in cholesteatoma (e.g. upregulation of matrix metalloproteinases, c and activation of angiogenesis). Other molecular findings clearly distinguish between cholesteatoma and malignant tumors (e.g., lack of chromosomal instability, intact checkpoint responses). To further distinguish the molecular mechanisms in cholesteatoma from malignant tumors, the authors determined telomerase activity and telomere length in both tissue types.

Methods: To evaluate the role of telomerase activation and telomere length in cholesteatoma, 29 cholesteatoma samples and 9 squamous cell carcinomas were analyzed for telomerase activity and telomere length. In addition, the rate of apoptosis was determined in both groups, using the TdT-mediated dUTP nick end labeling technique.

Results: As previously described, a high proportion of squamous cell carcinoma exhibited telomerase activity (6/9, 66%). By contrast, a significantly lower rate of telomerase activity was found in cholesteatoma samples (1/29, 3.4%, p = 0.0002). Despite the differences in telomerase activity, the telomere length was similar in cholesteatoma (mean length 7.43 kb) and in squamous cell carcinoma (mean length 7.99 kb; difference not significant, p = 0.1364). The low rate of telomerase activity in cholesteatoma was accompanied by significantly higher rates of apoptosis in cholesteatoma (mean 30%) compared with squamous cell carcinoma tissue (mean 3%, p = 0.0031).

Conclusions: Taken together, these data show that telomerase activation is a rare event in cholesteatoma and that the absence of telomerase activity is accompanied by high rates of apoptosis in cholesteatoma. It is proposed that the absence of telomerase limits the proliferative capacity of cholesteatoma by induction of apoptosis, whereas the presence of telomerase allows immortal growth of squamous cell carcinoma.