1. Gestational Trophoblastic Disease (GTD) Kang Yu Obstetric & Gynecology Hospital of Fudan Universtity 2013-11-26

2. Objectives Section I Brief Summary of GTD Section II Clinical Probation  Case I  Case II  Case III Section III Bedside-to-Bench ( and Back )  Trophoblast and cancer  Research design example

3. GTD is… A group of disorders in which trophoblastic tissue proliferates abnormally GTD includes: Benign Hydatidiform mole (complete or incomplete) Malignant (Gestational Trophoblastic Neoplasia, GTN) Invasive mole Choriocarcinoma Placental site trophoblastic tumor (PSTT)

4. GTN is remarkable because… One of the few malignant disease which can be cured Has very high rates of response to chemotherapy Has a tumor marker ( β- HCG ) that is… highly sensitive and 100% specific (normal pregnancy excluded)

5. Song Hongzhao (1915 - 2000 )  In 1994 was elected to the Chinese Academy of Engineering (Department of health)  In 1996 was elected an honorary fellow of British (London) the Royal College of obstetricians  Reduced the mortality rate of 从 horiocarcinoma from more than 90% to less than 15%

6. KEY TERMS AND DEFINITIONS Hydatidiform Mole. A placental abnormality involving swollen placental villi and trophoblastic hyperplasia with loss of fetal blood vessels. There are two types: complete and partial. Complete Mole. A molar pregnancy with swelling of all placental villi. Fetal tissues are absent. Partial Mole. A molar pregnancy with some normal and some swollen villi plus fetal, cord, and/or amniotic membrane elements.

7. KEY TERMS AND DEFINITIONS Invasive Mole. A variant of hydatidiform mole in which the hydropic villi invade the myometrium or blood vessels. It may spread to extrauterine sites. Choriocarcinoma. A morphologic term applied to a highly malignant type of trophoblastic neoplasia in which both the cytotrophoblast and syncytiotrophoblast grow in a malignant fashion. PSTT. A rare type of GTD arising in the uterus that secretes human placental lactogen (hPL) and human chorionic gonadotrophin (HCG).

8. Complete mole Partial mole

18. Section II Clinical Probation Case I Case II Case III

19. Section III Bedside-to-Bench (and Back) Trophoblast and cancer Research design example

20. Trophoblast invasion A successful pregnancy requires cytotrophoblasts invade the uterus, inclusive of its blood vessels, to establish efficient fetomaternal exchange of molecules. BACKGROUDBACKGROUD The role of trophoblasts

21. Cancer Metastasis Cancer metastasis is a multi-step process BACKGROUDBACKGROUD

22. The similarities of trophoblast and cancer High cell proliferation rate Lack of cell-contact inhibition Invasion Escape from immune detection Expression of common growth factors, cell adhesion molecules, matrix-digesting enzymes and proto-oncogene Express functional tumour-associated genes BACKGROUDBACKGROUD

24. 1 、 Why choriocarcinoma can be cured?  Biological properties of specific cancers (‘ seeds’) PUZZLES2PUZZLES2 Choriocarcinoma Other cancer Trophoblast

25. 2 、 Why choriocarcinoma readily metastasizes to lung? PUZZLES3PUZZLES3  The microenvironments of different organs are biologically unique. (‘soil’) Endothelial cells in the vasculature of different organs express different cell-surface receptors and growth factors Organ-specific

26. Trophoblast invasion Abortion IUGR Normal pregnancy Placenta implants ExcessiveInadequateAdequate 3 、 How trophoblast turn into choriocarcinama? Choriocarcinoma Invasiveness gradually reduced Proliferation Invasion matastasis Trophoblast invasion Normal pregnancy Adequate Trophoblast invasion Strictly regulated Highly controlled Trophoblast invasion Normal pregnancy Adequate Trophoblast invasion Excessive Choriocarcinoma Trophoblast invasion Normal pregnancy Adequate Trophoblast invasion Regulatory factors Out of control

27. 康玉 ykang@126.com