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AbstractWe have previously demonstrated the presence of human papillomavirus (HPV) DNA in several gynecological cancers using conventional PCR. In the present study, to further understand the role of HPV in malignant transformation of these cancers, the infection rates and viral loads of HPV 16 and 18 in gynecological cancers were analyzed using real-time quantitative PCR (qPCR). HPV 16 DNA was detected in 61.0% (58/95), 15.2% (7/46) and 32.1% (18/56) of cases of cervical, endometrial and ovarian cancers, respectively. On the other hand, HPV 18 DNA was detected in 23.2% (22/95) of cervical cancers, 1.8% (1/56) of ovarian cancers, and in no cases of endometrial cancer. Thus, HPV 16 is much more prevalent than HPV 18 in malignancies of the female genital tract. We also found that both HPV 16 and 18 were significantly (p < 0.05) less frequently present in endometrial and ovarian cancers than in cervical cancer. The median copy numbers of HPV 16 DNA in endometrial and ovarian cancers were 3,500 and 7,590 copies/μg DNA, respectively. These amounts were also significantly (p < 0.05) lower than HPV 16 DNA in cervical cancer (492,800 copies/μg DNA). Thus, HPV 16 could be detected in all three types of gynecological cancer, whilst HPV 18 is extremely rare in endometrial and ovarian cancers. The lower HPV 16 infection rates and lower copy numbers when compared with cervical cancer tend to suggest that HPV plays a less essential role in the development of endometrial cancer and ovarian cancer.Copyright © 2003 S. Karger AG, Basel

AimsTo investigate the pattern of telomerase activity in hydatidiform mole as compared with normal placenta and choriocarcinoma, and to determine the prognostic significance of telomerase activity in hydatidiform mole.MethodsTelomerase activity in 35 cases of hydatidiform mole, 35 normal placentas, one choriocarcinoma sample, and two choriocarcinoma cell lines (JAR, JEG3) was determined using the sensitive polymerase chain reaction based telomeric repeat amplification protocol (TRAP) assay. Two cases of breast carcinoma and two cases of ovarian carcinoma were also included as positive controls in the telomerase assay.ResultsTelomerase activity was detected in 11 of 30 early placentas (36.7%), one of five term placentas (20%), five of 27 hydatidiform moles which regressed spontaneously (18.5%), and six of eight hydatidiform moles which developed persistent trophoblastic disease (75%) (including three which developed metastases). Hydatidiform moles which subsequently developed persistent disease, especially those which metastasised, were more likely to express telomerase activity (p < 0.01). However, there was no significant difference in the frequency of telomerase activity between early placentas and hydatidiform mole. Strong telomerase activity was observed in choriocarcinoma tissue, choriocarcinoma cell lines, and ovarian and breast carcinomas.ConclusionsTelomerase activation occurs in hydatidiform mole with a similar incidence to early normal placentas. This supports the concept that hydatidiform mole is essentially an abnormal conceptus. There is an association between telomerase activation and the development of persistent trophoblastic disease. Further study is warrant to confirm the prognostic significance of telomerase activity in hydatidiform mole.

BackgroundThe p21^WAF1/CIP1 gene mediates growth arrest by inhibiting G₁ cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53.AimTo analyse the role of p21^WAF1/CIP1 in gestational trophoblastic disease.MethodsThe immunohistochemical expression of p21^WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress.Resultsp21^WAF1/CIP1 immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21^WAF1/CIP1 protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and chorio-carcinomas had a significantly higher p21^WAF1/CIP1 expression compared with normal placentas and partial hydatidiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21^WAF1/CIP1 expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21^WAF1/CIP1 expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not.ConclusionsThis study suggests that p21^WAF1/CIP1 expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21^WAF1/CIP1. p21^WAF1/CIP1 expression is not an accurate prognostic indicator of gestational trophoblastic disease.