Expression of human telomerase reverse transcriptase, the catalytic subunit of telomerase, is associated with the development of persistent disease in complete hydatidiform moles.

OBJECTIVE: This study was undertaken to determine the putative role of telomerase activity and human telomerase reverse transcriptase (hTERT) expression in the development of persistent disease in patients with a diagnosis of complete hydatidiform mole. The ribonucleoprotein telomerase has been shown to have a major role in the process of cellular immortality and carcinogenesis. The reactivation of this enzyme that occurs in the development of malignancies appears to be limited by the regulation of its catalytic subunit hTERT. Compared with their somatic counterparts, most human malignancies demonstrate telomerase activity, and this activity is dependent on the cellular presence of hTERT. The role of telomerase in the pathogenesis of complete hydatidiform moles is not clearly understood. Moreover, the role of hTERT in trophoblastic disease, as well as in the development of persistent trophoblastic disease, has yet to be elucidated.

STUDY DESIGN: Telomerase activity and hTERT expression were analyzed in the initial uterine evacuation specimen of 54 complete hydatidiform moles by use of the telomeric repeat amplification protocol assay and reverse transcription-polymerase chain reaction methods. The results were compared and then correlated with the development of persistent trophoblastic disease.

RESULTS: Among the 54 patients who were examined with a diagnosis of complete hydatidiform mole, persistent trophoblastic disease requiring postevacuation chemotherapy developed in 6. In the remaining 48 patients, spontaneous remission of the disease occurred after uterine evacuation. Both telomerase activity and hTERT expression were detected in all 6 cases of persistent disease on the initial molar tissue sampled. Among the 48 nonpersistent moles, telomerase activity was detected in 29 (60%) and hTERT expression was demonstrated in 26 (54%). The detection of hTERT expression was significantly associated with the presence of persistent disease (P =.035). Moreover, the absence of hTERT expression in molar tissue obtained from uterine evacuation demonstrated a 100% negative predictability in determining cases of complete mole that were nonpersistent.

CONCLUSIONS: Compared with telomerase activity, the expression of hTERT is significantly associated with the development of persistent disease in complete hydatidiform moles. The absence of hTERT expression in the initial tissue sample from complete moles may have potential clinical value in determining patients who will eventually undergo spontaneous remission after uterine evacuation.