Correlations Of Telomere Length And HTERT Expression In Ameloblastomas

ObjectiveTelomere is a group of tandem-repeat DNA sequences located at the ends of eukaryotic chromosomes.It is thought to stabilize chromosomes and protect them from end-to-end fusion or exonucleolytic degradation.Telomerase,a ribonucleoprotein complex consisting of a reverse transcriptase catalytic subunit(hTERT) and an RNA moiety(hTR) that provides the template along with enzymatic functions,adds TTAGGG repeats to the end of the chromosome.Telomerase has been shown to preferentially elongate the critically short telomeres,stabilize telomere lengths.More than 90%of tumor cells are found to have telomerase activity.Telomere dysfunction and telomerase activation play paradoxical roles in tumorigenesis.In the current study,we examined the telomere length of ABs with special reference to their clinical features,histologic findings,and hTERT activity in order to investigate whether the telomere length might predict the biologic characteristics of human ABs.Materials and methodsAll of the samples were selected from department of oral pathology,school of stomotology,china medical university in the period of 2001 to 2007.Include:normal oral mucosa(n=10),ameloblastomas(n=89) and oral squamous cell carcinoma(OSCC) (n=12).Telomere length was measured by fluorescence in situ hybridization(FISH) and hTERT protein and ki67 expression was examined by immunohistochemistry.ResultsThe intensity of fluorescence indicating telomere length was 0.2105±0.1334,0.1260±0.0886,0.0487±0.0295 in normal group,ABs group,and OSCC group,respectively.The telomere length in ABs group was markedly shorter than that in normal group(F=8.965,P=0.000).The telomere length was 0.1290±0.0973,0.1252±0.0794,0.1008±0.0556 in primary ABs group,recurred ABs group and malignant ABs group respectively(F=0.229,P=0.796).hTERT protein was positive in 2 of the 10 normal specimens(20%),64 of the 89 ABs specimens(71.9%) and in 11 of the 12 OSCC(91.7%).The positive ratio of hTERT protein in ABs group was higher than that in normal group(X~2＝154.45 9,P=0.0 00).Besides,hTERT positive rates increased as ABs recurred and transformed malignantly(X~2=32.517,P=0.000).The telomere length was 0.0965±0.0747,0.1364±0.0749 and 0.1401±0.1227 in hTERT(-) group, hTERT(+) group and hTERT(++) group,respectively.No correlation was found between hTERT expression and telomere length in ABs(F=1.984,P=0.144).ki67 expression increased as ABs recuured and transformed malignantly(F=4.344, P=0.017),but no relationship was observed between ki67 expression and tumor localization and histotype(F=0.762,P=0.520).The expression of ki67 was correlated with hTERT acitivation(r=0.282,P=0.023).However,it is noteworthy that there is an inverse correlation of ki67 expression and telomere length in ameloblastomas(r=-0.151,P=0.231).ConclusionTelomere attrition and hTERT activation may correlate with the development of human ameloblastomas.And the activation of an alternative mechanism for telomere lengthening may present in ameloblastomas.