Mcl-1 expression in gestational trophoblastic disease correlates with clinical outcome: a differential expression study.
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.
Fong
Pui-Yee
PY
Department of Pathology, Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Xue
Wei-Cheng
WC
Ngan
Hextan Y S
HY
Chan
Kelvin Y K
KY
Khoo
Ui-Soon
US
Tsao
Siu-Wah
SW
Chiu
Pui-Man
PM
Man
Lai-Shan
LS
Cheung
Annie N Y
AN
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015331:Cohort Studies; D018076:DNA, Complementary / Q000032:analysis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D031901:Gestational Trophoblastic Disease / Q000235:genetics / Q000473:pathology; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016015:Logistic Models; D008875:Middle Aged; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011336:Probability; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology*
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm