The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer.

The objective of this study was to identify the tumor characteristics associated with mismatch repair deficiency in young patients with endometrial carcinoma. Young patients (45 yr old or younger) with endometrial carcinoma treated by hysterectomy in our institution between July 2001 and June 2009 were identified. The clinical and pathologic data were obtained by review of clinical records. Among the 122 cases identified, paraffin sections were available in 67 cases for immunohistochemical staining and frozen tissue available in 62 cases for microsatellite instability (MSI) analysis. Both paraffin sections and frozen tissue were available in 36 cases. Among the 67 cases with immunohistochemical staining, 22 (32.8%) showed loss of expression of at least 1 mismatch repair protein. Defective MLH1 or MSH2 expression was associated with poor prognostic factors, including a higher incidence of pelvic lymph nodes metastasis (P=0.018) and higher stage (P=0.022) for MLH1, and an increased risk of lymphovascular permeation (P=0.015) for MSH2. On the contrary, defective MSH6 protein expression was associated with a lower incidence of high-grade tumors (P=0.04). Among the 62 cases with MSI analysis, 12 (19.4%) tumors were classified as microsatellite-high (MSI-H), whereas 2 (3.2%) were classified as microsatellite-low (MSI-L). There was no difference in the pathologic characteristics between MSI-stable and MSI-H tumor. We concluded that defective mismatch repair expression is important in young patients with endometrial carcinoma, with MSH6 protein being most commonly affected. The phenotype resulting from defective MSH6 expression was different from that caused by MLH1 or MSH2 loss.

Overexpression of forkhead box protein M1 (FOXM1) in ovarian cancer correlates with poor patient survival and contributes to paclitaxel resistance.

AIM: Deregulation of FOXM1 has been documented in various cancers. The aim of this study was to evaluate the role of FOXM1 in ovarian cancer tumorigenesis and paclitaxel resistance. EXPERIMENTAL DESIGN: Expression of FOXM1 was examined in 119 clinical samples by immunohistochemistry and correlated with clinicopathological parameters. Effects of FOXM1 knockdown on ovarian cancer cell migration, invasion and mitotic catastrophe were also studied. qPCR and ChIP-qPCR were used to establish KIF2C as a novel FOXM1 target gene implicated in chemoresistance. RESULTS: High nuclear FOXM1 expression in ovarian cancer patient samples was significantly associated with advanced stages (P = 0.035), shorter overall (P = 0.019) and disease-free (P = 0.014) survival. Multivariate analysis confirmed FOXM1 expression as an independent prognostic factor for ovarian cancer. FOXM1 knockdown significantly inhibited migration and invasion of ovarian cancer cells and enhanced paclitaxel-mediated cell death and mitotic catastrophe in a p53-independent manner. Bioinformatics analysis suggested a number of potential transcription targets of FOXM1. One of the potential targets, KIF2C, exhibited similar expression pattern to FOXM1 in chemosensitive and chemoresistant cells in response to paclitaxel treatment. FOXM1 could be detected at the promoter of KIF2C and FOXM1 silencing significantly down-regulated KIF2C. CONCLUSION: Our findings suggest that FOXM1 is associated with poor patient outcome and contributes to paclitaxel resistance by blocking mitotic catastrophe. KIF2C is identified as a novel FOXM1 transcriptional target that may be implicated in the acquisition of chemoresistance. FOXM1 should be further investigated as a potential prognostic marker and therapeutic target for ovarian cancer.

BRCA1 deficiency induces protective autophagy to mitigate stress and provides a mechanism for BRCA1 haploinsufficiency in tumorigenesis.

Stress adaptation has profound impacts on malignant progression and response to treatment. BRCA1 is an important modulator of cellular stress, but our understanding of its mechanisms of action remains incomplete. Here we identify autophagy as an essential mechanism protecting BRCA1 deficient cancer cells from metabolic stress and allow their survival, which may underlie its significant cancer-promoting properties. We showed that targeted inhibition of endogenous BRCA1 using small interfering RNA caused significant autophagy in response to serum starvation and endoplasmic reticulum stress, whereas overexpression of BRCA1 did not, confirming that the effect was BRCA1 specific. We demonstrated that Beclin 1 was activated in BRCA1 deficient cells, suggesting involvement of a canonical pathway. Importantly, BRCA1 deficient cells were highly dependent on autophagy for survival, and rapidly underwent cell death upon disruption of autophagy. Notably, this dependence on protective autophagy extended to their tissue of origin, as ovarian surface epithelial cells from women testing positive for BRCA1 mutations, in contrast to those with no mutations, robustly induced autophagy to mitigate the stress and promote their survival. These findings highlight a novel role for BRCA1 in protective autophagy, which may make its essential contribution to tumorigenesis and prognosis.

Assessment of knowledge and stigmatizing attitudes related to human papillomavirus among Hong Kong Chinese healthcare providers.

OBJECTIVE: To assess knowledge and stigmatizing attitudes related to human papillomavirus (HPV) and HPV testing among Chinese healthcare providers in Hong Kong. METHODS: Between May and September 2010, an anonymous self-administered questionnaire was sent to 247 doctors, nurses, and smear-taking trainees providing cervical screening in Hong Kong. RESULTS: In total, 137 questionnaires were returned. Most participants had basic knowledge about HPV infection and HPV vaccination. Only about 33% knew that high-risk HPV does not cause genital warts, infection is most common among young women, or infected individuals might not have any identifiable sexual risk factors. Regarding HPV testing, 6 of 7 knowledge items were answered incorrectly by many participants (≥ 50%), highlighting a lack of understanding of the indications for HPV testing and the implications of a positive result. About 30% of participants agreed that individuals with HPV infection were sexually easy, responsible for their infection, or had more than 1 sexual partner. More knowledge about HPV infection predicted less stigmatizing attitudes. CONCLUSION: Continued education on HPV and HPV testing is needed for frontline healthcare providers of screening in Hong Kong. The stigmatizing attitudes toward HPV-infected individuals warrant further exploration of the impact of HPV infection on patient care and interventions.

Human papillomavirus vaccine: what are women most concerned about?

AIM: This study aims to investigate the areas of concerns that women have regarding human papillomavirus (HPV) vaccination. MATERIAL AND METHODS: A cross-sectional questionnaire survey was conducted in a convenience sample of 1450 women attending outpatient family planning clinics in Hong Kong to assess women's concerns regarding HPV vaccination. The associations between each demographic characteristics and the importance of various issues concerning the vaccine, such as short and long-term side-effects, side-effect affecting appearance, number of women who have had it, effectiveness, effect duration and cost were explored using χ(2) tests for comparison of proportions. Multiple binary logistic regression analysis was applied to further identify independent demographic characteristics which were significantly associated with each of these issues. RESULTS: The top three factors that most women felt very important were vaccine effectiveness (45.4%), effect duration (44.0%) and long-term side-effects (43.7%). Education level significantly affected the degree of concerns in these areas (OR=1.15, P<0.001, 1.14, P<0.001 and 1.09, P=0.006, respectively) while income was significantly inversely associated with the importance of cost (OR=0.92, P<0.001) and effectiveness (OR=0.95, P=0.047). CONCLUSION: The above issues should be specifically addressed when vaccine information is given, bearing in mind the particular concerns in women with different socio-economic backgrounds.

Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival.

AIMS: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. METHODS AND RESULTS: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n = 5) and clinical samples of ovarian borderline tumours (n = 21) and invasive cancers (n = 108) when compared with ovarian epithelial cell lines (n = 3) and benign cystadenomas (n = 10) (P < 0.05). High Dock180 cytoplasmic expression in ovarian cancer (n = 108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P < 0.05), as well as poor overall and disease-free survival (P = 0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P < 0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. CONCLUSIONS: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target.

Prevalence and risk factors of Human Papillomavirus (HPV) infection in southern Chinese women - a population-based study.

BACKGROUND: Persistent high-risk type Human papillomavirus (HPV) infection is recognized as a necessary cause of cervical cancer. This study aimed to compare the HPV prevalence and risk factors between women residing in Hong Kong (HK) and Guangzhou (GZ) region of China. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1,570 and 1,369 women were recruited from HK and GZ, respectively. The cytology samples were collected and tested for HPV infection. The overall and type-specific HPV prevalence and the potential risk factors for acquisition of HPV infection were studied. Women with normal cytology in the GZ cohort had significantly higher HPV prevalence (10%) than those in the HK cohort (6.2%, p<0.001). The patterns of the age-specific HPV prevalence were also different between the two cohorts. In the HK cohort, women at the age of 20-29 years old had the highest prevalence and a second peak was observed in the age of ≥ 60 years old. In the GZ cohort, the highest HPV prevalence was also observed in 20-29 years old but declined as the age increased and a second peak was not seen. HPV16 and HPV52 were the most common high-risk types found in the HK and GZ cohorts, respectively. Age was the most consistently observed independent risk factor for HPV infection in the HK, while the number of sexual partners had association in the GZ cohort. CONCLUSIONS/SIGNIFICANCE: Our study provides the current status and the epidemiological characteristics of HPV prevalence in Southern Chinese women. The results strongly suggested that population education and the effective cervical cancer screening would be vital in the prevention of cervical cancer.

Psychological burden of testing positive for high-risk human papillomavirus on women with atypical cervical cytology: a prospective study.

OBJECTIVE: To assess the psychological burden of testing positive for high-risk human papillomavirus (HPV) on Chinese women with atypical squamous cells of undetermined significance (ASCUS). DESIGN: Prospective observational study. SETTING: Five community women's health clinics in Hong Kong. POPULATION: Ethnic Chinese women (n=299) with ASCUS who underwent reflex HPV testing (of whom 142 tested HPV negative and 157 tested HPV positive). METHODS: Women's psychological condition was assessed by self-administered questionnaires at smear result notification and by structured telephone interviews six months after notification. All women who tested positive for HPV were referred for colposcopy. MAIN OUTCOME MEASURES: State anxiety, cervical cancer worry and psychosocial burden. RESULTS: At result notification, the HPV-positive group had significantly higher state anxiety, cervical cancer worry and psychosocial burden than the HPV-negative group (all p<0.001). Irrespective of the HPV results, all outcome scores decreased over time. About 80% of the women who were HPV positive attended colposcopy as recommended. At six months, the two groups did not differ in state anxiety, cervical cancer worry, perceived risk of cervical cancer and satisfaction with intimate relationship, but psychosocial burden remained higher in the HPV-positive group (p=0.001). CONCLUSIONS: A concurrent positive HPV result intensified the distress of women with ASCUS at result notification. With time and after colposcopy, their initial heightened anxiety and cervical cancer worry were significantly lowered. However, HPV positivity may pose a prolonged psychosocial burden on women even after having had the necessary follow-up for their cervical abnormalities.

The effect of school-based cervical cancer education on perceptions towards human papillomavirus vaccination among Hong Kong Chinese adolescent girls.

OBJECTIVE: To evaluate the effects of school-based cervical cancer education on Hong Kong Chinese adolescent girls. METHODS: Adolescent girls (n=953) in local secondary schools attended a tailored educational program on cervical cancer prevention. Self-administered questionnaires were used before and after the program to measure its effects on participants' knowledge, attitude and perceived social norms towards human papillomavirus (HPV) vaccination and their intention to be HPV vaccinated. RESULTS: Before the program, HPV vaccine acceptance was favorable but relevant knowledge was low. After the program, participants had greater knowledge and a more positive attitude (both p<0.001), with more girls anticipating family (41.6% before vs. 58.9% after) and peer support (32.8% before vs. 56.9% after). There were 11.3% more girls who indicated an intention to accept the vaccine afterward. More knowledge, a more positive attitude and perceived support from significant others predicted a stronger intention to be HPV vaccinated. CONCLUSION: The educational program had a positive impact on participants' perceptions towards HPV vaccination and their intention to be vaccinated. PRACTICE IMPLICATIONS: School-based cervical cancer education is a viable means to meet the substantial educational needs of adolescents. Promotion of HPV vaccination should also include educating and influencing perceptions of families and peers.

Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers.

BACKGROUND: FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive. RESULTS: In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600 bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells. CONCLUSIONS: Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy.

Ovarian clear cell carcinoma with choriocarcinomatous differentiation: report of a rare and aggressive tumor.

Ovarian epithelial tumors of nongerm cell origin with true choriocarcinomatous differentiation are rare. To date, there are only 5 documented cases in the literature. In the reported cases, the epithelial component was of mixed cell types or of mucinous differentiation. To the best of our knowledge, an ovarian carcinoma exclusively of clear cell differentiation coexisting with a pure choriocarcinoma has not been reported earlier. A 48-year-old postmenopausal woman was found to have a large pelvic mass with lung and liver metastases. Trucut biopsy of the mass showed a poorly differentiated carcinoma that was immunoreactive for CK7 and hCG. She received 6 cycles of neoadjuvant chemotherapy that included 3 cycles of etoposide/cisplatin and 3 cycles of paclitaxel/etoposide-paclitaxel/carboplatin (TE/TP) with partial response. Debulking surgery was carried out subsequently. Pathologic examination showed an ovarian clear cell carcinoma with a second component of choriocarcinoma in which the bilaminar growth pattern of cytotrophoblast and syncytiotrophoblasts was striking. Despite additional therapy, which included 2 cycles of TE/TP and 2 cycles of gemcitabine/taxotere, the disease progressed and the patient died 11 months postoperatively. This report showed that ovarian clear cell carcinoma with choriocarcinomatous differentiation is a highly aggressive tumor and has a very poor prognosis. Nonetheless, there may be a role for neoadjuvant chemotherapy that targets both the clear cell and the choriocarcinoma components to reduce the volume of the disease before debulking surgery.

p21-activated kinase 4 regulates ovarian cancer cell proliferation, migration, and invasion and contributes to poor prognosis in patients.

Ovarian cancer is a lethal gynecological malignancy, and to improve survival, it is important to identify novel prognostic and therapeutic targets. In this study, we present a role for p21-activated kinase 4 (Pak4) in ovarian cancer progression. We show a significant association between increased expression of Pak4 and its activated form, phosphorylated (p)-Pak4 Ser(474), with metastasis of ovarian cancers, shorter overall and disease-free survival, advanced stage and high-grade cancers, serous/clear cell histological subtypes, and reduced chemosensitivity. Pak4 overexpression was also observed in ovarian cancer cell lines. Pak4 and p-Pak4 expression were detected both in the nucleus and cytoplasm of ovarian cancer cells, in vitro as well as in vivo. Stable knockdown of Pak4 in ovarian cancer cell lines led to reduced cell migration, invasion, and proliferation, along with reduced c-Src, ERK1/2, and epidermal growth factor receptor (EGFR) activation and decreased matrix metalloproteinase 2 (MMP2) expression. Conversely, Pak4 overexpression promoted ovarian cancer cell migration and invasion in a c-Src, MEK-1, MMP2, and kinase-dependent manner, and induced cell proliferation through the Pak4/c-Src/EGFR pathway that controls cyclin D1 and CDC25A expression. Stable knockdown of Pak4 also impeded tumor growth and dissemination in nude mice. This report reveals the association between Pak4 and important clinicopathologic parameters, suggesting Pak4 to be a significant prognostic marker and potential therapeutic molecular target in ovarian cancer. The implied possible cross-talk between Pak4 and EGFR suggests the potential of dual targeting of EGFR and Pak4 as a unique therapeutic approach for cancer therapy.

Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy.

Uterine smooth muscle tumors are classified according to their morphologic features that include architecture, growth pattern, cellular characteristics and constituents of the intercellular stroma. While terminologies used for the pathologic diagnosis of various subtypes may be eloquent and histologically accurate, some of these are confusing for the clinician and may also be open to interpretation by different pathologists: the labeling of atypical leiomyomas epitomizes this intricate system. Clinically, it is probably more useful to classify them as either tumors with or tumors without recurrent and/or metastatic potential. The term "atypical leiomyoma" has been used to label tumors that have a low risk of recurrence and is synonymous with benign tumors. The latter are known variously as leiomyoma with bizarre nuclei, symplastic leiomyoma, or pleomorphic leiomyoma. Variants of benign uterine smooth muscle tumors, such as mitotically active leiomyoma, cellular and highly cellular leiomyoma, epithelioid leiomyoma, and myxoid leiomyoma each have distinctive hallmarks that enable subclassification. Nevertheless, they may occasionally possess one or more unusual features that are cause for alarm. Tumors that have a dissecting growth pattern, with or without extrauterine extension, may mimic malignancy both grossly and microscopically. The current review discusses the pathologic diagnosis of and terminology applied to selected variants of uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas with emphasis on unusual reported features that may indicate malignancy. This includes an update on uterine smooth muscle tumor of uncertain malignant potential (STUMP), intravenous leiomyomatosis, benign metastasizing leiomyoma, and diffuse leiomyomatosis. Their clinicopathologic features, differential diagnoses, and management options based on findings in the previously reported cases will also be reviewed.

De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial.

OBJECTIVE: To identify the components of a human papillomavirus (HPV) message contributing to reducing the stigma of HPV in cervical cancer. METHODS: 294 ethnic Chinese women attending a community-based clinic in Hong Kong were randomly allocated to read one of three written HPV messages: Group 'lr+hrHPV': low-risk and high-risk HPVs facts, Group 'hrHPV': high-risk HPV facts only and Group 'ds+hrHPV': high-risk HPV facts and de-stigmatising components, namely being anti-stereotypical, motivational and low in complexity. Main outcome measures were high-risk HPV-related sexual stigma, knowledge, attitude towards message, and intention to be HPV-tested measured by self-administered questionnaires immediately before and after reading. RESULTS: Message allocation had a significant effect on sexual stigma (F = 5.219, p = 0.006). Participants who read message ds+hrHPV showed the least stigma, and were significantly less likely to believe that high-risk HPV infection implicated promiscuity, non-monogamy or that monogamy offered complete protection against high-risk HPV. The genital HPV-focused message was more stigmatising than cervical cancer-focused messages. Of all participants, 93% (237/254) and 97% (260/269) indicated a positive intention to be HPV-tested before and after reading, respectively. There were no between-group differences noted in terms of knowledge and intention to be HPV-tested before or after reading. CONCLUSIONS: Our findings show that an HPV message containing specific de-stigmatising components may reduce public stigma towards high-risk HPV. Also, focusing solely on high-risk HPV in the context of cervical cancer helps to avoid the stigmatising effect of genital warts from tainting perceptions about high-risk HPV infection.

Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: effects on prognosis and cell invasion.

Ovarian cancer is a gynecological malignancy with high mortality. Therefore, the identification of novel prognostic and therapeutic targets is important. p21-activated kinases (Paks) are involved in cytoskeleton reorganization. This study investigated the clinical significance of total and phosphorylated (p) Pak1 and Pak2 as well as their functional roles in ovarian cancer. Expressions of Pak1, p-Pak1 Thr(212), Pak2 and p-Pak2 Ser(20) in ovarian normal and cancerous cell lines as well as in clinical samples of ovarian tumors were evaluated. The effects of Pak1 and Pak2 on ovarian cancer cell functions were determined. Pak1, p-Pak1 and p-Pak2 were overexpressed in ovarian cancer cell lines, and clinical samples of ovarian cancers were compared with benign ovarian lesions/inclusion cysts. Similar Pak2 expression levels were observed among normal and cancerous cell lines and clinical samples. After multiple testing correction, high Pak1 and nuclear p-Pak1 expression in ovarian cancers was significantly associated with histological type and tumor grade, respectively. Pak1 and p-Pak1 expression was associated with poor overall and disease-free survival. Pak1 was an independent prognostic factor. Knockdown of Pak1 and Pak2 in ovarian cancer cell lines reduced cell migration and invasion but did not affect cell proliferation and apoptosis. Knockdown of Pak1 also reduced p38 activation and downregulated vascular endothelial growth factor. Conversely, ectopic Pak1 overexpression enhanced ovarian cancer cell migration and invasion in a kinase-dependent manner, along with increased p38 activation. Our findings suggest that Pak1, p-Pak1 and p-Pak2 play important roles in ovarian carcinogenesis. Pak1 and p-Pak1 may be potential prognostic markers and therapeutic molecular targets in ovarian cancer.

Epigenetic alteration of the metallothionein 1E gene in human endometrial carcinomas.

Aberrant expression of metallothioneins (MTs) has been observed in several human tumors. In our microarray analysis, MT-1E was found to have much lower expression in endometrial cancer cells as compared with other types of cancer cells generated from the cervix, ovary or prostate. The result was confirmed by quantitative RT-PCR analysis of the MT-1E levels in individual cancer cells. Treatment of endometrial cancer cells with 5-azacytidine could reactivate MT-1E expression. We further analyzed the DNA methylation status of the promoter region of MT-1E using methylation-sensitive restriction enzymes HhaI and HpaII, followed by PCR. Promoter hypermethylation was detected in 42.4% (53/125) of the endometrial carcinoma samples, whilst none of the 38 normal tissues or hyperplasia samples were methylated. The mRNA levels of MT-1E were significantly lower in the methylation-positive than in the methylation-negative samples. Endometrial carcinoma samples with low MT-1E expression coincidently had low levels of estrogen receptor-alpha expression and vice versa. This phenomenon was not observed in the expression pattern between estrogen receptor-beta and MT-1E. There was no significant correlation between MT-1E methylation and any clinical parameters. In conclusion, a high frequency of cancer-specific hypermethylation of MT-1E was found in endometrial carcinomas. Its functional consequence in the development of endometrial cancer warrants further investigation.

Tyrosine kinase B receptor and BDNF expression in ovarian cancers - Effect on cell migration, angiogenesis and clinical outcome.

In this report, we demonstrated that overexpression of tropomyosin-related kinase B (TrkB) was associated with shorter survival in ovarian cancer patients. Brain-derived neurotrophic factor (BDNF), the TrkB ligand, induced activation (phosphorylation) of TrkB in a dose dependent manner. Besides demonstrating the effect of BDNF/TrkB pathway in enhancing cancer cell migration and invasion but inhibiting apoptosis, we also report for the first time that exogenous hepatocyte growth factor induced TrkB expression at both mRNA and protein levels as well as phosphorylation. Our findings suggest that BDNF/TrkB pathway is important in ovarian carcinogenesis and TrkB may be a potential therapeutic target for ovarian cancer.

Coexistence of struma ovarii with marked ascites and elevated CA-125 levels: case report and literature review.

INTRODUCTION: Struma ovarii is a rare form of ovarian neoplasm and consists mainly of thyroid tissue. Ascites has been reported in approximately one-third of all the cases. However, the combination of struma ovarii and elevated CA-125 has rarely been reported. MATERIALS AND METHODS: We described a case of benign struma ovarii, presenting with the clinical features of ovarian cancer: large complex pelvic mass, gross ascites and markedly elevated serum CA-125 levels. Surgical excision of the ovarian mass was followed by rapid resolution of the ascites and reduction of the serum CA-125 level. CONCLUSION: Struma ovarii can mimic ovarian malignancy clinically, when presented with ascites and an elevated CA-125 level.

Promoter methylation of death-associated protein kinase and its role in irradiation response in cervical cancer.

This study was aimed at investigating the death-associated protein kinase (DAPK) promoter methylation and its clinical relevance in cervical cancer. The DAPK promoter methylation was detected by methylation-specific PCR (MSP) and correlated with DAPK mRNA and protein expression. The effect of DAPK expression on the radiosensitivity of the cervical cancer cell line was assessed by overexpressing DAPK in the radioresistant cell line SiHa. DAPK hypermethylation was found in 56.08% of the cervical cancer samples and was associated with the tumor histological cell type of squamous cell carcinoma (p=0.002) and advanced tumor stage (p=0.005). Subsequently, DAPK protein expression was found to significantly decrease in cervical cancer samples when compared to normal tissues. The DAPK mRNA and protein expression levels were absent or remarkably reduced in SiHa and HeLa in which the DAPK promoter was hypermethylated. The expression levels of DAPK could be restored after demethylation treatment with 5-aza-2'-deoxycytidine. Overexpressing DAPK in vitro had no significant influence to the survival of the radioresistant SiHa cell after being challenged by irradiation. Our findings suggest that DAPK might not directly be responsible for the cellular radiosensitivity, however, DAPK hypermethylation appeared to be of prognostic significance in the advanced stages of cervical cancer.

Beliefs about cervical cancer and human papillomavirus (HPV) and acceptability of HPV vaccination among Chinese women in Hong Kong.

OBJECTIVE: To assess the knowledge and beliefs on cervical cancer and HPV infection and to evaluate the acceptability of HPV vaccination among Chinese women. METHODS: Seven focus groups were conducted with ethnic Chinese women aged 18-25 (n=20), 26-35 (n=13), and 36 and above (n=16) in a community women's health clinic in Hong Kong in 2006. The discussions were audio taped, transcribed and analyzed. Recurrent themes related to cervical cancer, HPV infection and vaccination were highlighted. RESULTS: Diverse conceptions on likely causes of cervical cancer were noted, covering biological, psychological, environmental, lifestyle and sexual factors. Most women had not heard of HPV and its mode of transmission. The participants had difficulties understanding and accepting the linkage between cervical cancer and the sexually transmitted HPV infection. HPV infection was seen as personally stigmatizing with significant adverse impact on self-esteem and significant relationships. Participants favored HPV vaccination both for themselves and their teenage daughters if authoritative endorsement was provided. CONCLUSION: Inadequate knowledge and misconceptions on cervical cancer and HPV were common. Most participants welcomed and favored having HPV vaccination. Apart from promoting HPV vaccination, cervical cancer prevention should also include strategies to promote knowledge and minimize the stigmatizing effect of a sexually transmitted HPV infection.