Biomedical subjects

K Y K Chan

Publications and source records attributed to K Y K Chan.

7 recordsLinked to original sources

PubMed2006

Single nucleotide polymorphisms of follicle-stimulating hormone receptor are associated with ovarian cancer susceptibility.

Epidemiological studies suggested that ovulation was associated with ovarian carcinogenesis. Follicle-stimulating hormone (FSH) played an important role in follicular development and was recently found to affect growth of ovarian epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser were two non-synonymous variations in the coding region of the FSH receptor (FSHR) gene. This hitherto first case-control study investigating the association between these two FSHR SNPs and the risk of ovarian cancer involved 202 histopathologically confirmed ovarian cancer patients and 266 age-matched cancer-free control subjects using restriction fragment length polymorphism assay and direct sequencing. Our results demonstrated that the 307Ala and 680Ser carriers were associated with significantly increased risk of developing serous and mucinous types of ovarian cancers (P < 0.0005, OR = 2.60, 95% CI = 1.56-4.34; and P < 0.0005, OR = 2.89, 95% CI = 1.73-4.84, adjusted for age, respectively) but not endometrioid and clear cell types. The two SNPs were found to be in modest linkage disequilibrium, D' = 0.804 and 0.701, r2 = 0.581 and 0.406 for the cancer and control groups, respectively. The major haplotype of 307Ala-680Ser was also associated with higher cancer risk (P = 0.033, OR = 1.39, 95% CI = 1.03-1.88), especially for the serous and mucinous carcinomas (P = 0.001, OR = 1.82, 95% CI = 1.27-2.60). Our results suggested that the two FSHR SNPs might affect the susceptibility of women to specific subtypes of ovarian cancer. Different types of ovarian cancer might adopt distinct carcinogenetic pathways. Such understanding may be important in selecting patients for ovulation induction therapy.

Base Sequence↗

PubMed2006

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

BACKGROUND: Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified. AIMS: To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis. METHODS: cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed. RESULTS: Downregulation of caspase 10 in choriocarcinoma was detected by both Atlastrade mark human cDNA expression array and Atlastrade mark human 1.2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p < 0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p = 0.003, respectively) approaches. CONCLUSIONS: These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.

Apoptosis↗

PubMed2005

Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis.

AIMS: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues. METHODS AND RESULTS: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients.

Adolescent↗

PubMed2005

Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease.

AIMS: To assess the expression of Id proteins in trophoblastic tissues and to correlate this with clinical parameters, proliferative and apoptotic indices as well as to related oncogene expression. METHODS AND RESULTS: Immunohistochemistry for Id1, Id2, Id3 and Id4 was performed on 83 trophoblastic tissues including 17 normal first-trimester placentas, seven term placentas, 47 hydatidiform moles (HM), and 12 spontaneous miscarriages. The four Id proteins were predominantly expressed in the villous and implantation site intermediate trophoblast. Expression of Id1 in HM was significantly higher than that in normal placenta (P = 0.0006) and spontaneous miscarriage (P = 0.0001) but did not correlate with subsequent development of gestational trophoblastic neoplasia (GTN). Id1 expression correlated with the proliferation index as assessed by MCM7 (P = 0.003) and Ki67 (P = 0.017) and with the apoptotic activity assessed by TUNEL (P = 0.001) and M30 CytoDeath antibody (P = 0.013). Moreover, the expression of Id1 correlated with the expression of p53 (P = 0.004), p21(WAF1) (/CIP1) (P = 0.003) but not with p16 (P = 0.107). CONCLUSIONS: Id proteins may play a role in the regulation of proliferative and apoptotic activity in trophoblastic tissue and are potentially useful in differentiating molar and non-molar gestation, but are not helpful in predicting GTN.

Cell Cycle Proteins↗

PubMed2004

Detection of hypermethylated genes in tumor and plasma of cervical cancer patients.

OBJECTIVE: The aim of this study is to investigate the prevalence of promotor CpG island methylation of the death-associated protein kinase (DAPK), p16, and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in both tumor and plasma samples of cervical cancers. METHODS: Methylation-specific PCR (MSP) was employed to detect promotor CpG island methylation of the DAPK, p16, and MGMT genes in 85 surgical tumor tissue samples and 40 pretreatment plasma samples from cervical cancers. RESULTS: Promotor CpG island methylation of DAPK, p16, and MGMT was detectable, respectively, in 60%, 28.2%, and 18.8% of cases of cervical tumor DNA; and in 40%, 10%, and 7.5% of cases of patients' plasma DNA. Moreover, at least one of the three methylated genes was detected in 75.3% (64/85) of cases of tumor and in 55% (22/40) of cases of plasma. Higher prevalence of methylation of DAPK was found in squamous cell carcinoma than in adenocarcinoma in both univariate and multivariate analysis. Methylation of p16 was significantly associated with that of MGMT in both univariate and multivariate analysis. The methylation pattern in primary tumor and plasma was found to be concordant in 23 patients with matched tissue and plasma samples. In cases positive for DAPK and p16 methylation in tumor, detection in the paired plasma sample was 64.3% (9/14) and 33.3% (3/9), respectively. CONCLUSIONS: Promotor CpG island methylation is a frequent event in cervical carcinogenesis. Detection of the methylated sequences in the circulation suggests that plasma DNA methylation warrants further study to determine its potential role in cancer management.

Adult↗

PubMed2003

Minichromosome maintenance protein 7 expression in gestational trophoblastic disease: correlation with Ki67, PCNA and clinicopathological parameters.

AIMS: To assess the proliferative activity of gestational trophoblastic disease (GTD) using one of the novel proliferation markers (MCM7) and to determine its prognostic value in hydatidiform mole (HM). METHODS AND RESULTS: Immunohistochemical staining for MCM7 was performed on 122 samples of paraffin-embedded trophoblastic tissues including 22 normal first-trimester placentas, 12 term placentas, 12 spontaneous miscarriages (SM), 21 partial moles (PM), 44 complete hydatidiform moles (CM), and 11 choriocarcinomas (CCA). The correlations between the proliferative indices assessed by MCM7, proliferating cell nuclear antigen (PCNA) and Ki67 (MIB1) immunoreactivity as well as clinical progress were assessed. MCM7 immunoreactivity was found predominantly in the nuclei of cytotrophoblast and intermediate trophoblast and decreased with placental maturation. MCM7 expression was highest in CCA, followed by CM, PM, normal first-trimester placenta, SM and term placenta. MCM7 index was significantly higher in PM and CM than in SM (P = 0.007, P < 0.001) but not between PM and CM themselves (P = 0.560). Eighteen of the 65 patients with HM developed persistent trophoblastic disease (PTD) requiring chemotherapy. There was no significant difference in MCM7 indices between the patients who developed PTD and those who did not (P = 0.312). MCM7 indices correlated well with Ki67 (P = 0.002) but not with PCNA (P = 0.054) indices. MCM7 indices demonstrated less variability than PCNA and Ki67 and may be a better proliferation marker than the latter two. CONCLUSIONS: We conclude that MCM7 is useful in differentiating molar and non-molar gestations but is not helpful in discriminating PM from CM or in predicting PTD.

Biomarkers, Tumor↗

PubMedDate not supplied

Methylation status and expression of E-cadherin and cadherin-11 in gestational trophoblastic diseases.

The clinical significance of cadherins in gestational trophoblastic diseases (GTD) is not fully understood. In this study, the expression of E-cadherin and cadherin-11 in 12 normal placentas, 32 cases of hydatidiform mole (HM) including 15 complete HMs and 17 partial HMs, and five choriocarcinomas was investigated by immunohistochemistry and correlated with follow-up of HMs. Cases with available frozen blocks were further analyzed by western blot and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Methylation of E-cadherin was investigated by methylation-specific PCR in six normal first trimester placentas, 19 HMs and their associated deciduas. E-cadherin expression was localized to cytotrophoblast and intermediate trophoblast whereas cadherin-11 was expressed in syncytiotrophoblast, intermediate trophoblast, and decidua. Immunoreactivity of E-cadherin was reduced in choriocarcinoma and complete HM when compared with that in normal first trimester placenta (P < 0.01, P = 0.04). Hypermethylation of E-cadherin was demonstrated in three complete HMs with the lowest level of E-cadherin. Compared with normal first trimester placenta, immunoreactivity of cadherin-11 was higher in complete HM (P = 0.02), but lower in choriocarcinoma (P = 0.02). Such differential expression was confirmed by western blot and semiquantitative RT-PCR. No obvious association was observed between the development of persistent trophoblastic disease with the expression of E-cadherin and cadherin-11.

Adult↗