MOLECULAR AND IMMUNOHISTOCHEMICAL CHARACTERISTICS OF COMPLETE HYDATIDIFORM MOLES
Kubelka-Sabit KB1,*, Prodanova I2, Jasar D1, Bozinovski G3, Filipovski V1, Drakulevski S1, Plaseska-Karanfilska D3
*Corresponding Author: Dr. Katerina B. Kubelka-Sabit, Clinical Hospital Acibadem Sistina, Skupi 5a, 1000 Skopje, Republic of Macedonia. Tel: +389-70-365-338. Fax: +389-23-099-599. E-mail: catkubelka@ yahoo.co.uk; katerina.kubelka@acibademsistina.mk
page: 27

RESULTS

Histopathological Analyses. In all eight complete moles, chorionic villi with irregular jagged villous contours, heterogenous population of chorionic villi, stromal edema, mucous stromal degeneration and trophoblastic nuclear atypia were found. Circumferential trophoblastic proliferation was found in 7/8 (87.5%) cases, whereas cytotrophoblastic proliferation was present in 5/8 (62.5%) cases. Karyorrhectic stromal debris was present in 2/8 (25.0%) of the cases (Table 2). On the other hand, when compared to the defined histopathological criteria for partial hydatidiform mole there was only a slight overlap (Table 3). In fact, two types of villi or presence of fetal erythrocytes were not found in any of the cases, whereas focal trophoblastic proliferation and trophoblastic stromal inclusions were present in one of the cases. On the other hand, irregular villous contours were seen in all eight cases. Immunohistochemistry. In all eight complete mole cases, the Ki-67 proliferation index was higher than 50.0% (Table 4, Figure 3). There was a complete absence of positivity for the p57 immunohistochemical marker in the cytotrophoblasts and villous stromal cells in all cases, irrespective of the genetic origin of the chromosomes (Table 4, Figure 4). For the p63 marker, the percentage of stained cytotrophoblasts was between 60.0 and 80.0% in all eight cases (Table 4, Figure 5). In one case, the staining intensity was weak, in three it was moderate, whereas a strong staining signal was observed in four cases. Molecular Analyses. The QF-PCR analysis was performed in all eight cases. Androgenetic diploidy was found in seven of them (87.5%), whereas in one case, the genetic analysis showed biparental diploidy. According to the clinical data obtained for this patient, she had previously suffered seven early miscarriages. The last three products of conception were submitted for analysis in our laboratory. They all showed histopathological evidence of early complete molar pregnancy and were biparental diploidies with a 46,XX genotype. In fact, the initial curettage submitted for analysis was due to persistent complete mole, for which the patient was treated with methotrexate. After 1 year, the next pregnancy also showed histopathological evidence of complete molar pregnancy, with chromosomal characteristics of biparetal diploidy. One year later, after the third miscarriage with complete molar phenotype and biparental diploidy genotype, this patient was considered as a possible case of familial recurrent hydatidiform mole. Due to the supposed clinical syndrome and repeated molar pregnancies, the patient was consulted against future spontaneous pregnancies and was offered in vitro fertilization with oocyte donation. She was also referred for further genetic investigation about her condition. The second patient was diagnosed in the 15th week of gestation with a twin pregnancy. Apart from the normal fetus, the patient had a complete molar pregnancy. She was treated with methotrexate due to elevated β human chorionic gonadotropin (bHCG) serum levels. Seventeen months later, a resection of the left uterine horn was performed due to suspected ruptured left cornual pregnancy. The material submitted for histopatohhological analysis consisted of soft, hemorrhagic and partially necrotic tumorous tissue. Subsequent microscopic analysis revealed that the tumor had morphological characteristics of placental site trophoblastic tumor. It had infiltrated the myometrium and had given numerous vascular emboli. In order to accurately assess the risk category of the placental site trophoblastic tumor, we had to prove whether it originated from the previous complete molar pregnancy. Therefore, QF-PCR analysis was performed on the placental tissue sample from the complete molar pregnancy and from the tumor tissue. The genetic profiles of both placental and tumor tissue were identical, thus proving that the tumor originated from the placental mole. Therefore, the patient was classified in the low risk category. After excluding metastatic disease, the patient underwent total hysterectomy with bilateral adnexectomy. She is alive and without disease after 14 months of follow-up. The follow-up period of the other six patients was uneventful.



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