Indoleamine 2,3-dioxygenase expression in gestational trophoblastic disease: implications for development of immunotherapeutic approaches.

OBJECTIVE: To examine the immunoexpression of indoleamine 2,3-dioxygenase (IDO) in gestational trophoblastic neoplasia (GTN), including hydatidiform moles and gestational trophoblastic tumors. STUDY DESIGN: GTN cases were identified from a referral center for trophoblastic disease, and sections were immunostained with anti-IDO antibody and classified as positive or negative for trophoblast staining relative to normal chorionic villi. RESULTS: Fifty-two cases were included: 10 nonmolar hydropic miscarriages (HA), 11 partial moles (PHM), 9 complete moles (CHM), 15 choriocarcinoma cases (CC) and 7 placental site trophoblastic tumors (PSTT). All HA, PHM and CHM demonstrated IDO staining; 2 of 15 CC were strongly positive, 6 demonstrated focal positivity (< 10% of tumor cells), and the remainder were negative. Of the 7 PSTT, only 2 showed focal weak positivity; the others were negative. CONCLUSION: Hydatidiform moles express IDO, but the majority of gestational trophoblastic tumors, despite arising from villous or nonvillous trophoblast, do not express this enzyme, suggesting that IDO-mediated immunoregulation is unlikely to be a major component of the malignant phenotype in these tumors. Immunotherapeutic approaches involving IDO might represent ancillary approaches in a minority of patients with GTN.

Management and outcome of healthy women with a persistently elevated beta-hCG.

PURPOSE: Raised serum beta human chorionic gonadotrophin (beta-hCG) not due to pregnancy can occur as a consequence of (1) gestational trophoblastic neoplasia (GTN), (2) non-gestational trophoblastic tumours, (3) a false-positive beta-hCG, (4) the menopause or (5) a high normal level. Accurate differentiation between these causes is vital to avoid potentially inappropriate investigations and therapies, which may induce infertility or other serious adverse events. Here we report the United Kingdom experience of patients with an elevated beta-hCG of initial uncertain cause and provide a clinical algorithm for the management of such cases. METHOD: The Charing Cross and Weston Park Hospital GTN databases were screened to identify patients referred with an elevated beta-hCG who were not pregnant and had no previous diagnosis of GTN. RESULTS: Between 1981 and 2004 fourteen women presented with persistently raised serum beta-hCG resulting in diagnostic problems. False-positive beta-hCG was excluded in all. Three patients developed gestational choriocarcinoma after 9-29 months. However, in 11 women no cause for the persistently elevated beta-hCG was found. One of these achieved chemotherapy-induced normalisation of serum beta-hCG, but the remaining 10 underwent surgery and/or chemotherapy without benefit. Thus, 71% (10/14) of patients remain well with unexplained elevated beta-hCG levels. CONCLUSION: Elevated serum and urinary beta-hCG levels in healthy women should be investigated systematically to exclude an underlying malignant process and to avoid inappropriate surgical and medical intervention. Long-term follow-up is required as tumours may not become apparent for many months or years.