The impact of molecular genetic diagnosis on the management of women with hCG-producing malignancies

Abstract

Objectives: The diagnosis of a gestational trophoblastic tumour (GTT) should be considered in all women presenting with a malignancy and an elevated human chorionic gonadotrophin (hCG) level. Whilst some non-gestational malignancies can also produce hCG, most non-gestational tumours can be distinguished from GTT on the basis of histopathological examination. However, some non-gestational tumours can exhibit trophoblastic differentiation and so make establishing the definitive diagnosis difficult. In these cases, molecular genetic investigation can establish the differential diagnosis between gestational and non-gestational tumours and facilitate optimal management. The objective of this study is to demonstrate the clinical value of distinguishing these two diagnoses by genetic analysis in patient care at a major GTT treatment centre.

Methods: Between 1994 and 2005, fluorescent microsatellite genotyping was used to examine the genetic origin of 35 cases of metastatic hCG-producing tumours with trophoblastic differentiation, three cases of atypical uterine tumours, three cases of uterine choriocarcinoma with a very long interval and one atypical ovarian tumour.

Results: Of the 42 cases examined, 24 were proved to be of gestational origin, 14 were non-gestational and in 4 cases genetic analysis was inconclusive. We illustrate the clinical value of this diagnostic technique by presenting five individual cases in which molecular genetic results helped determine the appropriate clinical management.

Conclusion: Analysis of the genetic origin of atypical hCG-producing tumours in women allows the optimisation of individual patient care and should be considered in the management of these unusual cases.