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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

20-year experience of managing profuse bleeding in gestational trophoblastic disease.

OBJECTIVE: To review the outcomes of different methods in the treatment of severe bleeding or acute abdomen in gestational trophoblastic disease (GTD). STUDY DESIGN: In a tertiary referral center, the records of patients diagnosed with GTD and presenting with heavy vaginal bleeding or acute abdomen between January 1986 and December 2005 were retrieved. RESULTS: Seventeen patients presenting with heavy bleeding or acute abdomen and requiring emergency management were identified. Ten patients had heavy vaginal bleeding, and 7 had shock or signs of hemoperitoneum. Eleven patients had total abdominal hysterectomy with or without bilateral salpingo-oophorectomy (TAH +/- BSO), 2 had arterial ligation, 3 had embolization, and 1 had suturing of a vaginal defect due to a metastatic nodule. The median ages of the patients having TAH +/- BSO and other conservative treatments were 37 (21-52) and 32.5 (26-48), respectively. Fifteen patients received chemotherapy after surgical treatment. All patients survived except 1, who died of concurrent disease. CONCLUSION: Profuse bleeding in GTD is rare. Hysterectomy, arterial ligation and angiographic embolization can effectively treat this condition. With more experience, angiographic embolization should be the treatment of choice, especially for those who are hemodynamically stable and wish to retain their fertility potential.

Methotrexate, bleomycin, and Etoposide in the treatment of gestational trophoblastic neoplasia.

OBJECTIVE: The combination of methotrexate (1 g/m(2) day 1), bleomycin (10 mg day 3), and etoposide (100 mg/m(2) days 1-5) (MBE) has been used for disease relapse or as a second-line chemotherapy in the treatment of gestational trophoblastic neoplasia (GTN) resistant to multiple-agent chemotherapy. With the identification of ultra-high-risk GTN, MBE has also been used as first-line chemotherapy. The current study is to review the use of MBE in the treatment of GTN. METHODS: Patients who received MBE for GTN between 1985 and 2003 in Queen Mary Hospital were included in this study. Records were reviewed and data were analyzed. Outcomes including response rate, treatment complications, and survival were assessed. RESULTS: Methotrexate, bleomycin, and etoposide therapy was given as first line to 4 patients with ultra-high-risk GTN. Three responded to the treatment and remained disease free. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who had drug resistance to the initial therapy. Seven responded, and 6 remained disease free at 5 years. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who relapsed 2-18 months after their initial therapy. Seven patients responded, and 4 remained disease-free at 5 years, 2 defaulted, and one died of carcinoma of the colon. Of the 20 patients who received MBE, 12 developed grade 3/4 neutropenia, and 4 developed grade 3/4 thrombocytopenia. The overall response rate for MBE was 85%. CONCLUSION: Methotrexate, bleomycin, and etoposide should be considered as a second-line therapy in patients who have drug-resistant or recurrent GTN.

Single-dose methotrexate regimen in the treatment of low-risk gestational trophoblastic neoplasia.

OBJECTIVE: The objective of the study was to evaluate the effectiveness of single-dose methotrexate in women with low-risk gestational trophoblastic neoplasia. STUDY DESIGN: In this prospective observational cohort study, 105 women with low-risk gestational trophoblastic neoplasia were treated with an intravenous bolus of 100 mg/m2 of methotrexate followed by a 12-hour infusion of 200 mg/m2. If the human chorionic gonadotropin level fell 10-fold after 2 weeks, no further chemotherapy was given. Characteristics between the 2 groups with or without complete remission with this regimen were compared. RESULTS: The overall complete remission rate with methotrexate was 84.8%, with 44.8% of women requiring a single dose of methotrexate alone. The pretreatment human chorionic gonadotropin level was found to be significantly higher in women who failed the single-dose methotrexate regimen (P = .001), and 10 of 11 patients with metastases required further doses. CONCLUSION: This regimen offers an effective option for women with low-risk gestational trophoblastic neoplasia without metastases and a low pretreatment human chorionic gonadotropin level.

Relapsed gestational trophoblastic neoplasia: A 20-year experience.

OBJECTIVE: To review relapsed gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Patients who had relapsed GTN between 1978 and 2001 at Queen Mary Hospital were included in the study. Records were reviewed and data analyzed regarding treatment, follow-up and survival. RESULTS: Eighteen patients with relapsed GTN were identified. Patients' ages ranged from 21 to 56 years, with a median of 34. Eight were classified as low risk, 1 as medium risk and 9 as high risk at the time of diagnosis. Seven, 3 and 8 patients were treated with single-, dual- and multiple-agent chemotherapy, respectively. The median interval between remission and relapse was 6.5 months (range, 1-132). The time interval to relapse did not correlate with patient mortality (Mann-Whitney U test, p = 0.873). Four patients died of the disease, and all of them were classified and treated as low risk at the time of diagnosis. Three were lost to follow-up at some point. The remaining patient had relapsed choriocarcinoma and developed progressive disease despite intensive multiple-modality treatment. The overall survival rate for relapsed GTN was 77.8%. CONCLUSION: Patients with relapsed GTN are salvageable. Failure of treatment seems attributable to patients who defaulted treatment or follow-up and presented late with massive disease.

p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy.

Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy. By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy (P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients (P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression (P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women.

OBJECTIVE: To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. RESEARCH DESIGN AND METHODS: A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. RESULTS: The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. CONCLUSIONS: Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.

Maternal hemoglobin and risk of gestational diabetes mellitus in Chinese women.

OBJECTIVE: To examine the relationship between high maternal hemoglobin concentration at the initial antenatal visit and occurrence of gestational diabetes mellitus (GDM) in the third trimester in nonanemic women. METHODS: In a prospective observational study, 762 nondiabetic Chinese women with singleton pregnancies, whose initial visit hemoglobin concentration and mean cell volume were 10 g/dL or more and 80 fL or more, respectively, recruited at 28-30 weeks, had blood drawn for repeat measurement of hemoglobin concentration and iron parameters. These women were categorized by their initial visit hemoglobin concentration into quartiles, and the incidence of GDM was analyzed together with the maternal characteristics and iron status. RESULTS: The final study sample comprised 730 women. Compared with the rest, the group in the highest hemoglobin quartile (more than 13 g/dL) had a significantly higher incidence of GDM (18.7% versus 10.9%, P =.007), as well as greater age, weight, and serum ferritin and iron concentrations. Logistic regression was used to examine the effects of high body mass index (more than 25 kg/m(2)), advanced age (older than 34 years), parity of 1 or more, and hemoglobin in the highest quartile, on the incidence of GDM. Only advanced age (odds ratio 3.79, 95% confidence interval 2.33, 6.17) and hemoglobin in the highest quartile (odds ratio 1.73, 95% confidence interval 1.08, 2.78) emerged to be significant factors. CONCLUSION: A high maternal hemoglobin (more than 13 g/dL) at the initial prenatal visit in Chinese women is an independent risk factor for GDM. This may reflect a better nutritional status in these women, as suggested by the increased iron status.