ABSTRACT
<p><b>OBJECTIVE</b>To study the expression of the small subunit ribonucleotide reductase (R2) in gestational trophoblastic diseases (GTD) and to assess its prognostic value.</p><p><b>METHODS</b>The expression of R2 was detected with immunohistochemical method in 15 cases of normal villi, 38 cases of hydatidiform mole (HM), 42 cases of invasive moles (IM) and 18 cases of choriocarcinoma (CC).</p><p><b>RESULTS</b>R2 expression in HM, IM and CC was significantly increased compared with that of normal villi (P=0.000). There were no significant differences in R2 protein expression among HM, IM and CC. Among 38 cases of HM, R2 expression in 8 cases with malignant transformation was significantly higher than in 30 cases of non-malignant transformation mole (P=0.02). Preoperative chemotherapy of gestational trophoblastic tumor including IM and CC did not influence the R2 expression. Compared with patients of stage I (WHO), the R2 protein in gestational trophoblastic tumor (GTT) patients of stage III or stage II was significantly increased (P=0.023 and P=0.038, respectively). The value of R2 in GTT patients with middle or high risk in WHO prognostic scoring system was higher than in the patients with low risk (P=0.018 and P=0.006, respectively).</p><p><b>CONCLUSION</b>R2 expression in GTD is increased, which may be associated with the hyperplasia of trophoblasts, malignant transformation of hydatidiform mole and drug resistance of trophoblastic tumor.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Gestational Trophoblastic Disease , Pathology , Ribonucleotide Reductases , Genetics , Uterine Neoplasms , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the relationship of changes in gene expression profiles of hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts.</p><p><b>METHODS</b>The differentially expressed genes were analyzed in two pairs of tissues of hydatidiform mole versus normal villi, and in two pairs of normal primary culture trophoblasts versus JAR cell line of chariocarcinoma, using cDNA microarray containing 4096 genes. To confirm the results of cDNA microarray analysis, expressions of some up-regulated genes related to DNA synthesis in normal villi, hydatidiform mole, and 2 choriocarcinoma cell lines (JAR and JEG-3) were examined by immunohistochemistry, immunoblotting and RT-PCR.</p><p><b>RESULTS</b>A total of 89 genes were differentially expressed in all hydatidiform moles, accounting for 2.2% of the genes arrayed. Of the 89 genes, 24 were up-regulated and 65 were down-regulated. Compared with normal primary trophoblasts, there were 433 genes up-regulated and 380 genes down-regulated in JAR cell line. Forty six genes were up-regulated in both hydatidiform mole and choriocarcinoma, while 13 genes were down-regulated. Some genes associated with cell proliferative inhibition were significantly down-regulated, whereas those associated with cell proliferation, malignant transformation, metastasis and drug resistance were highly up-regulated. The expressions of thymidine kinase 1, the small subunit of ribonucleotide reductase (RRM2) were significantly increased in hydatidiform mole, JAR and JEG-3 cells.</p><p><b>CONCLUSION</b>Abnormal expression of genes exists in hydatidiform mole and choriocarcinoma. Hyperplasia of trophoblasts may be related to over-expression of genes coding for synthetic enzymes.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic , Choriocarcinoma , Genetics , Metabolism , Pathology , Drug Resistance, Neoplasm , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Hydatidiform Mole , Genetics , Metabolism , Hyperplasia , Neoplasm Metastasis , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction , Ribonucleoside Diphosphate Reductase , Metabolism , Thymidine Kinase , Metabolism , Trophoblasts , Pathology , Uterine Neoplasms , Genetics , Metabolism , PathologyABSTRACT
<p><b>OBJECTIVE</b>To determine candidate genes of endometrial adenocarcinoma.</p><p><b>METHODS</b>To compare the gene expression profile in 2 endometrial adenocarcinoma tissues and 2 normal endometria by HGEC-40s GeneChip probe including 4096 genes array. Expression differences between normal and malignant tissue groups were measured by GenePixPro3.0 software.</p><p><b>RESULTS</b>350 genes with a ratio below 0.5 and above 2.0 showed discrimination between normal and malignant groups. Thirty three genes with ratio above 3 were up-regulated, forty-four genes with ratio below 0.3 were down-regulated.</p><p><b>CONCLUSION</b>The overexpression of oncogenes with their disturbed or constitutively activated signal transduction cascades alone or in combination with the mutation-induced silencing of tumor suppressor genes is associated with malignant transformation.</p>