Mcl‐1 expression in gestational trophoblastic disease correlates with clinical outcome

Abstract

BACKGROUND Hydatidiform moles (HMs) are abnormal pregnancies with a propensity for developing persistent disease in the form of gestational trophoblastic neoplasia (GTN), which requires chemotherapy. In previous studies, the authors demonstrated that low apoptotic activity was correlated with the progression of HM to GTN, and they hypothesized that some apoptosis‐related genes may determine this progression. METHODS The differential expression of apoptotic genes in HMs that subsequently developed into GTN was compared with the same expression in HMs that spontaneously regressed using a human apoptosis array; then, the expression was evaluated with real‐time quantitative polymerase chain reaction analysis and immunohistochemistry using 54 clinical samples from patients with HMs who had follow‐up data available. RESULTS Using an apoptosis array, greater expression of Mcl‐1, which is an antiapoptotic gene, was detected in HMs that subsequently developed into GTN. It was confirmed that the levels of Mcl‐1 RNA expression (P = 0.017) and Mcl‐1 protein expression (P < 0.001) in HMs that developed into persistent disease and required chemotherapy were significantly greater compared with the levels in HMs that regressed. Moreover, Mcl‐1 immunoreactivity, which was detected predominantly in cytotrophoblasts, was correlated with the apoptotic index, as assessed with M30 cytoDeath immunohistochemistry, which is a good indicator of apoptotic events in the early‐stage disease. CONCLUSIONS The current results demonstrated that Mcl‐1, as identified by a cyclic DNA array, may play a role in the pathogenesis of HMs and may have potential as a useful marker for predicting the clinical behavior of HMs. Cancer 2005. © 2004 American Cancer Society.

Downregulation of ASPP1 in gestational trophoblastic disease: correlation with hypermethylation, apoptotic activity and clinical outcome

“…22,23,37 In this study, we found an inverse correlation between ASPP1 expression and clinical progress of hydatidiform moles. It is possible that the progressive loss of proapoptotic ASPP1 expression hinders the usual enhanced apoptosis in cytotrophoblasts and villous intermediate trophoblasts, leading to the development of persistent gestational trophoblastic neoplasms.…”

Differential expression of insulin‐like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia

“…Total RNA was extracted from frozen tissue by Trizol (Invitrogen, Carlsbad, CA) with integrity checked by gel electrophoresis. 10 Only samples with rRNA (28S/18S) ratio between 1.8 and 2 were used.…”

“…Our study using the Atlas™ Human Apoptosis Array (Clontech; Palo Alto, CA), which includes 205 cDNA related to apoptosis, identified Mcl-1 to be a predictive factor for GTN. 10 By using combined cDNA suppression subtractive hybridization (SSH) technique and microarray analysis in the current study, we attempted to expand the identification of differentially expressed genes in HM that subsequently developed GTN when compared with HM that spontaneously regressed. 11 The SSH technique is sensitive and efficient for generating cDNA highly enriched for differentially expressed genes with both high and low abundance, because this technique combines both the suppression PCR amplification and cDNA subtraction, leading to generation of two subtractive libraries.…”

Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study

“…2 6 7 Recently, we used apoptotic cDNA arrays, and identified Mcl-1, an apoptosis related gene, as being related to the clinical progression of HM. 8 In our present study, we compared the gene expression profiles of normal first trimester placentas and choriocarcinoma cell lines using more comprehensive cDNA arrays, followed by confirmatory gene expression studies by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The results were correlated with the clinicopathological and biological parameters in an attempt to improve our understanding of the pathogenesis of GTD.…”