• HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in

• Treatment of metastatic invasive moles in two husband-side sisters-in-law. Case reports and review of literature.

• Reduced expression of tissue inhibitor of metalloproteinase (TIMP)-2 in gestational trophoblastic diseases.

• Falsely elevated human chorionic gonadotropin leading to unnecessary therapy.

• Serum activin A and inhibin A. New clinical markers for hydatidiform mole.

1
UI - 12131159
AU - Singer G; Kurman RJ; McMaster MT; Shih IeM
TI - HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis.
SO - Am J Surg Pathol 2002 Jul;26(7):914-20
AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
HLA-G is a nonclassical MHC class I antigen that has been shown to be a specific marker for normal intermediate trophoblast (IT). In this study HLA-G immunoreactivity assessed with an HLA-G specific antibody (4H84) was detected in all 14 cases of choriocarcinoma, 14 placental site trophoblastic tumors, 13 epithelioid trophoblastic tumors, 16 placental site nodules, and nine exaggerated placental sites. In contrast, HLA-G immunoreactivity was not detected in 34 nontrophoblastic uterine neoplasms. HLA-G immunoreactivity was present in all the IT cells of exaggerated placental sites and placental site trophoblastic tumors and in 70-100% of IT cells in placental site nodules and epithelioid trophoblastic tumors. The pattern of distribution of HLA-G in different subpopulations of IT confirms the relationship of various trophoblastic lesions to different types of IT (exaggerated placental site and placental site trophoblastic tumor to implantation site IT and placental site nodule and epithelioid trophoblastic tumor to chorionic-type IT) and suggests that choriocarcinoma is related to villous-type IT because the majority of mononucleate cells in this neoplasm were HLA-G immunoreactive. In conclusion, HLA-G immunoreactivity appears to be specific for IT in gestational trophoblastic disease and can serve as a useful marker in the differential diagnosis of these lesions.

2
UI - 11874069
AU - Van Eijkeren MA; Sijmons EA; Witteveen PO; Verhaar MJ; Sie-Go DM; Heintz
TI - AP Treatment of metastatic invasive moles in two husband-side sisters-in-law. Case reports and review of literature.
SO - Eur J Gynaecol Oncol 2001;22(6):406-8
AD - Department of Obstetrics and Gynecology, University Medical Center, Utrecht, The Netherlands.
PURPOSE OF INVESTIGATION: The treatment of "high risk" persistent trophoblastic disease (PTD) consists of poly-chemotherapy. This policy probably will lead to overtreatment of some patients. Also, familiar molar pregnancies through the paternal line are unknown in the literature up till now. METHODS: We describe two cases of "high risk" PTD in two husband-side sisters-in-law, in which poly-chemotherapy was stopped after histology became available and showed invasive metastatic mole. CONCLUSION: It should be stressed that treatment decisions should be made based on the concept of "high" or "low" risk PTD, but if histology becomes available, chemotherapy might be less aggressive in cases of invasive mole. If invasive mole could be familiar through the paternal line remains unclear with the current knowledge of genetics in trophoblastic disease.

3
UI - 11912288
AU - Okamoto T; Niu R; Yamada S; Osawa M
TI - Reduced expression of tissue inhibitor of metalloproteinase (TIMP)-2 in gestational trophoblastic diseases.
SO - Mol Hum Reprod 2002 Apr;8(4):392-8
AD - Department of Obstetrics and Gynaecology, Chukyo Hospital, Nagoya, Japan. kmottm8@hotmail.com
To elucidate the involvement of type IV collagenases [matrix metalloproteinase (MMP)-2 and MMP-9] and their tissue inhibitors (TIMP-1 and TIMP-2) in the development of gestational trophoblastic disease (GTD), we quantified their levels in hydatidiform mole and choriocarcinoma tissues using specific enzyme-linked immunosorbent assays, and the results were compared with those from normal first trimester placenta. Levels of pro-MMP-2 were increased in hydatidiform mole, and they were further elevated in choriocarcinoma. Levels of pro-MMP-9 in choriocarcinoma and those of TIMP-1 in both hydatidiform mole and choriocarcinoma were also increased. In contrast, TIMP-2 levels were markedly decreased in both hydatidiform mole and choriocarcinoma. Similar results were obtained by the tissue culture of first trimester placenta and hydatidiform mole. Gelatin zymography indicated that the levels of both pro- and activated forms of MMP-2 and MMP-9 were higher in hydatidiform mole and choriocarcinoma. The decreased expression of TIMP-2 in hydatidiform mole and choriocarcinoma was confirmed by Western blot, Northern blot and immunohistochemistry, with the decrease being more pronounced in choriocarcinoma. Taken together, the present study shows that both TIMP-2 mRNA and protein levels are markedly decreased in GTD and the imbalance of MMP-TIMP production, shifted toward greater MMP activity, may be involved in the pathogenesis of GTD.

4
UI - 11864687
AU - Butler SA; Cole LA
TI - Falsely elevated human chorionic gonadotropin leading to unnecessary therapy.
SO - Obstet Gynecol 2002 Mar;99(3):516-7

5
UI - 12173329
AU - Florio P; Severi FM; Cobellis L; Danero S; Bome A; Luisi S; Petraglia F
TI - Serum activin A and inhibin A. New clinical markers for hydatidiform mole.
SO - Cancer 2002 May 15;94(10):2618-22
AD - University of Siena, Siena, Italy.
BACKGROUND: Although human placenta is a well established, rich source of proteins, hCG is the only measurement available to date in diagnosing the occurrence of the hydatidiform mole. Serum levels of a new placental protein, immunoreactive inhibin, were high in molar pregnancy, but the inhibin assay never became of clinical use, due to its low specificity and reliability. Since specific assays are now available for inhibin A, inhibin B, and activin A, the current study evaluated whether and which of these placental proteins is increased in presence of a molar pregnancy. METHODS: Serum inhibin A, inhibin B, activin A, and hCG levels were assayed in: A) 6 women with molar pregnancies, before and after evacuation; B) 37 healthy pregnant women; and C) 22 healthy nonpregnant women. RESULTS: Women with partial hydatidiform moles had significantly higher serum levels of inhibin A (P < 0.001) and activin A (P < 0.001) than healthy pregnant women, several fold higher than the 95% confidence interval of control values. After evacuation, the levels of both inhibin A (P < 0.001) and activin A (P < 0.05) declined significantly to the levels of nonpregnant controls. Molar hCG concentrations were significantly higher than in normal pregnancy (P < 0.001), but some values within the 95% confidence interval of normal values. Despite a significant decrease (P < 0.05) after evacuation, hCG levels were still higher than in nonpregnant women. CONCLUSIONS: The present data strongly suggest that serum inhibin A and activin A measurement may be of value in diagnosis and short-term follow-up of molar pregnancy.

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