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Nuclear ß-catenin and Ki-67 expression in choriocarcinoma and its pre-malignant form

¹ Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
² Department of Pathology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, China
³ Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

Correspondence to:
Dr S C Cesar Wong
Room 430, 4^th Floor, Sir Y K Pao Cancer Centre, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China; cesar{at}clo.cuhk.edu.hk Objective: To study the expression of nuclear ß-catenin and Ki-67 in patients with normal gestation products (NGP), complete hydatidiform moles (CHM), and choriocarcinoma to elucidate their roles in carcinogenesis and their interrelations.

Methods: Expression of nuclear ß-catenin and Ki-67 was studied by immunohistochemistry using paraffin embedded blocks. Sixty NGP, 60 CHM, and 10 choriocarcinomas were analysed. In addition, approximately 400 trophoblasts each in 40 NGP, 40 CHM, and 10 choriocarcinomas from the same batch of samples were microdissected for quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) to compare ß-catenin mRNA concentration among them.

Results: In the chorionic villi of NGP, ß-catenin was consistently expressed in the nuclei of cytotrophoblasts but not syncytiotrophoblasts. Nuclear ß-catenin expression was comparatively reduced in CHM trophoblasts and was absent in choriocarcinoma. By contrast, Ki-67 expression was increased from cytotrophoblasts but not in syncytiotrophoblasts in the chorionic villi of NGP to CHM trophoblasts and choriocarcinoma. Using Q-RT-PCR, ß-catenin mRNA was detected in 10 NGP, 13 CHM, and three choriocarcinoma specimens, with median copy numbers of 43 230, 18 229, and 17 334 per 400 trophoblasts, respectively. A housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was detected as a control in the NGP, CHM, and choriocarcinoma specimens, with median copy numbers of 51 300, 54 270, and 97 150 per 400 trophoblasts, respectively. Thus median ß-catenin mRNA values after normalisation were 0.85 in NGP (n = 10), 0.31 in CHM (n = 13), and 0.16 in choriocarcinoma (n = 3).

Conclusions: Decreased nuclear ß-catenin expression and increased Ki-67 expression may be involved in choriocarcinoma carcinogenesis. The findings also suggest that nuclear ß-catenin may play a role in trophoblast differentiation during normal placental development.

Abbreviations: ß-hCG, ß-human chorionic gonadotropin; CHM, complete hydatidiform mole; DEPC, diethylpyrocarbonate; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IHC, immunohistochemistry; NGP, normal gestation products; PHM, partial hydatidiform mole

Keywords: nuclear ß-catenin; hydatidiform mole; choriocarcinoma; cytotrophoblast; normal gestation products

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