HPV16-E6/E7 Oncogene Mutation and p53 Expression among Indonesian Women with Cervical Cancer.

OBJECTIVE: To characterize HPV16 E6/E7 mutation and its association with p53 expression among Indonesian women with cervical cancer. METHODS: This is a cross-sectional study involving 31 Indonesian women with pathologically proven cervical cancer and HPV16 infection. Data about the clinical characteristics of the study population were obtained from the medical records. Biopsy specimen of the cervical cancer mass from each study participant was obtained for DNA isolation. The ORFs of E6 and E7 genes were amplified using specific primer designed according to K02718/HPV16R gene sequence obtained from GenBank. Sequencing was performed using software program MEGA10. HPV16 E6 and E7 prototype sequences for nucleotide alignment (HPv16. P, GenBank Access code: NC_001526) was selected from European variant. The sequence of nucleotide and amino acid was aligned using software program BioEdit. p53 expression was evaluated through immunohistochemistry and quantified using immunoreactivity score (IRS). RESULTS: Twelve subjects (38.7%) present with E6 and E7 mutation. Median age, parity, stage and histologic type of the tumour did not associate with E6/E7 mutation. E6 and E7 mutation rate was 25.8% (8/31) and 12.9% (4/31), respectively. Seven single nucleotide changes were identified within the E6 and E7 oncogenes, including four non-synonymous and three synonymous mutations. E6 T27C was the most prevalent mutation (16.1%). Nonsynonymous mutations were more prevalent within E7 gene (9.6%) (N29T, N29S, and R77C). Median IRS did not differ between HPV16-E6/E7 variants and wildtype (p value = 0.990). There was no association between E6/E7 mutations and p53 expression in Indonesian women with cervical cancer (PR 1.4, 95% CI: 0.29-6.77, p value = 0.704). CONCLUSIONS: HPV16 E6 mutation was more prevalent than E7 mutation among Indonesian women. There was no association between E6/E7 mutation and p53 expression level.

Diagnostic accuracy of serum insulin-like growth factor-binding protein 2 for ovarian cancer.

INTRODUCTION: Insulin-like growth factor-binding protein 2 (IGFBP2) plays an important role in the pathogenesis of ovarian cancer. The most prominent effects of IGFBP2 include promoting proliferation, driving invasion, and suppressing apoptosis. This study aimed to determine the diagnostic accuracy of serum IGFBP2 in differentiating between benign and malignant ovarian neoplasms. METHODS: Preoperative serum IGFBP2 level was evaluated from 76 women with primary ovarian tumor who underwent exploratory laparotomy at Sanglah General Hospital, Denpasar, Bali, Indonesia. The optimal threshold value of IGFBP2 for the diagnosis of ovarian cancer was determined from the receiver 0perating characteristic (ROC) curve. The diagnosis was confirmed by histopathologic analysis of resected ovarian specimens. RESULTS: Forty-six (60.5%) patients were diagnosed with ovarian cancer. The area under the ROC curve (AUC) of IGFBP2 in detecting ovarian cancer was 0.815 (95% CI: 0.721 to 0.910, P<0.001). For a given specificity larger than 95%, the optimal sensitivity was 63%. The optimal threshold value of IGFBP2 for the diagnosis of ovarian cancer was 804 ng/mL [sensitivity 63%, specificity 96.7%, positive predictive value (PPV) 96.7%, negative predictive value (NPV) 63%, accuracy 76.3%, and diagnostic odd ratio (DOR) 49.5 (95% CI 6.1 to 396.5)]. In a subgroup analysis, IGFBP2 showed excellence performance in diagnosing advanced ovarian cancer (AUC 0.904 [95% CI: 0.806 to 1.000], sensitivity 83.3%, specificity 96.7%, PPV 95.2%, NPV 87.9%, accuracy 90.7%, and DOR 145.0 [95% CI 15.0 to 1395.3]). CONCLUSION: IGFBP2 is a novel and potentially promising biomarker for detecting ovarian cancer. Further studies are needed to confirm its diagnostic performance in premenopausal women and for detecting early stage ovarian cancer.

The role of caspase-dependent and caspase-independent pathways of apoptosis in the premature rupture of the membranes: A case-control study.

BACKGROUND: Premature rupture of membrane (PROM) remains a problem in obstetrics, the mechanisms of PROM have not been clearly defined. Apoptosis is thought to play a key role in the mechanism, via caspase-dependent and caspase-independent pathways. Caspase-3, Apoptosis-inducing factor (AIF), and anti-apoptosis B-cell lymphoma 2 (Bcl-2) are hypothesized to be involved in PROM. OBJECTIVE: To determine the role of caspase-dependent and caspase-independent pathways in the mechanism of PROM. MATERIALS AND METHODS: This was a case-control study involving 42 pregnant women with gestational age between 20-42 wk. Participants were divided into the case group (with PROM) and control group (without PROM). Amniotic membranes were collected immediately after the delivery, and samples were taken from the site of membrane rupture. Immunohistochemical examination was done to determine the expression of Caspase-3, AIF, and Bcl-2. RESULTS: The expressions of Caspase-3 (OR = 9.75; 95% CI = 2.16-43.95; p = 0.001) and AIF (OR = 6.60; 95% CI = 1.48-29.36; p = 0.009) were significantly increased, whereas, Bcl-2 expressions (OR = 8.00; 95% CI = 1.79-35.74; p = 0.004) were significantly decreased in the case group. CONCLUSION: High Caspase-3, AIF, and low Bcl-2 expression were the risk factors for PROM. Thus, it is evident that caspase-dependent and caspase-independent pathways are involved in the mechanism of PROM.

Low expression of collagen type-1 in sacrouterine ligament as risk factor of stage III-IV uterine prolapse.

BACKGROUND: Despite being non-life threatening, uterine prolapse is a reproductive health problem that interferes psychosocial life, economical and sexual function. Uterine prolapse can be caused by direct trauma resulting in damaged and weakened levator ani muscle which in turn causing sacrouterine ligament to stretch in order to maintain uterus normal position. The main component of sacrouterine ligament is collagen. Types of collagen that was involved in the occurrence of uterine prolapse are which plays a role of risk of occurrence uterine prolapse is collagen type-1 and type-3. Collagen type-1 has a good resistance and flexible to strain. If there is a disruption in the expression of collagen in sacrouterine ligament, it will result in cause uterine prolapse. OBJECTIVE: The aim of this study is to prove low expression of collagen type-1 in sacrouterine ligament is a risk factor for the occurrence of stage III-IV uterine prolapse. STUDY DESIGN: This study was an observational study using case-control approach. A total of 22 cases of stage III-IV uterine prolapse and 22 cases of non-uterine prolapse as control group were selected by consecutive sampling. This study was carried out in Sanglah General Hospital and Pathobiology Laboratory of Veterinary Faculty of Udayana. Samples were taken from sacrouterine ligament of individual with stage III-IV uterine prolapse compared to non-prolapse uterine who had undergone total hysterectomy. RESULTS: Chi-square analysis with 95 % confidence interval indicated that low expression of collagen type-1 was 6 times more likely to be the risk factor of stage III-IV uterine prolapse (OR = 5.95; 95 %CI = 1.59-22.33; p = 0.006). CONCLUSION: Low collagen type-1 in sacrouterine ligament is a risk factor of stage III-IV uterine prolapse.

Pulsatility Index and Hypoxia Inducible Factor-1α Expression Predict the Clinical Response after External Radiation in Patients with Stage IIB to IVA Cervical Cancer.

Objective: To evaluate the ability of pulsatility index (PI), resistance index (RI), and hypoxia inducible factor-1α (HIF-1α) expression in predicting the clinical response after radiation in patients with cervical cancer. Methods: A prospective cohort was carried on in Department of Obstetric and Gynecology Dr. Hasan Sadikin Hospital/ Faculty of Medicine, Padjadjaran University, during the period of July 2017 to March 2018 which include 51 samples with stage IIB to IVA cervical cancer. Tumor perfusion and oxygenation were evaluated using color Doppler ultrasound indices (pulsatility index and resistance index) and the expression of hypoxia inducible factor-1α (HIF-1α). The clinical response was assessed 2 months after external radiation. Result: Among 51 patients, 31 patients demonstrated good response and 20 patients demonstrated poor response to radiation. The mean value of PI was significantly lower in patients who demonstrated good response as compared to patients with poor response (0.84±0.916 vs. 1.70±1.260, p = 0.004). The mean value of RI did not differ significantly (0.29±0.112 vs. to 0.36±0.189 p =0.173). HIF-1α expression was significantly lower in patients who demonstrated good response as compared to patients with poor response (1.83±1.529 vs. 6.55±2.625, p = 0.0001). In multivariate model, PI and HIF-1α expression both predicted the clinical response after radiation. Conclusion: PI and HIF-1α expression predict the clinical response after radiation in patients with cervical cancer.

Management Comprehensive Multidisciplinary of Malignant Ovarian Germ Cell Tumors and Feto - Maternal Outcome: A Case Series Report and Literature Review.

BACKGROUND: Malignant Ovarian Germ Cell Tumors (MOGCT) most commonly occur in young women in the reproductive age group. Timely antenatal diagnosis and treatment of the tumour to enhance maternal and perinatal outcomes are the main challenges confronting the obstetrician and the gyne-oncologist. CASE PRESENTATION: Here we present three cases of pregnancy complicated with MOGCTs. The first case (immature teratoma) was complicated by maternal psychological symptoms consistent with stress and histopathological examination confirmed the diagnosis of premature ovarian failure (POF). The second case (dysgerminoma) preterm labour occurred as an obstetric complication, but the baby was born in good condition without IUGR. The third case (yolk sac tumour) treated with docetaxel (brexel)-carboplatin chemotherapy administration there was no maternal or fetal complication. At the end of the pregnancy and delivery, complete surgical staging and cytoreduction were performed, and no metastases were found. CONCLUSION: Optimal management strategies centre on a multi-disciplinary comprehensive team approach is critical resulting in better outcomes for the mother and the baby by avoiding complications.

The Role of Caspase-3, Apoptosis-Inducing Factor, and B-cell Lymphoma-2 Expressions in Term Premature Rupture of Membrane.

OBJECTIVE: To determine the role of caspase-3, apoptosis-inducing factor (AIF), and B-cell lymphoma-2 (Bcl-2) expressions in term premature rupture of membrane (PROM). METHODS: An analytic observational study with case-control design was conducted, involving 52 subjects (37-42 weeks of gestation) who were divided into 2 groups: 26 cases of term delivery with PROM, and 26 controls of term delivery without PROM. The expressions of caspase-3, AIF, and Bcl-2 in the amniotic membrane were determined by immunohistochemistry. Data were analyzed using the chi-squared test. The risk of PROM was expressed by odds ratio (OR). RESULTS: There were no significant differences in age, parity and body mass index between the two groups (p > 0.05). High caspase-3 and AIF expressions increased the risk of PROM 17.64 times (OR = 17.64; 95% CI = 4.44-70.07; p = 0.001) and 9.45 times (OR = 9.45; 95% CI= 2.62-34.07; p = 0.001), respectively, while low Bcl-2 expression increased 10.39 times (OR = 10.39; 95% CI = 2.73-39.56; p = 0.001)the risk of PROM . CONCLUSION: High caspase-3 and AIF expressions and low Bcl-2 expression were risk factors for term PROM. Caspase-dependent and independent pathways of apoptosis were involved in the mechanism of PROM in term pregnancy.

The role of caspase-3, apoptosis-inducing factor, and B-cell lymphoma-2 expressions in term premature rupture of membrane

Abstract Objective To determine the role of caspase-3, apoptosis-inducing factor (AIF), and Bcell lymphoma-2 (Bcl-2) expressions in term premature rupture of membrane (PROM). Methods An analytic observational study with case-control design was conducted, involving 52 subjects (37-42 weeks of gestation) who were divided into 2 groups: 26 cases of term delivery with PROM, and 26 controls of term delivery without PROM. The expressions of caspase-3, AIF, and Bcl-2 in the amniotic membrane were determined by immunohistochemistry. Data were analyzed using the chi-squared test. The risk of PROM was expressed by odds ratio (OR). Results There were no significant differences in age, parity and body mass index between the two groups (p > 0.05). High caspase-3 and AIF expressions increased the risk of PROM 17.64 times (OR = 17.64; 95% CI = 4.44-70.07; p = 0.001) and 9.45 times (OR = 9.45; 95% CI= 2.62-34.07; p = 0.001), respectively, while low Bcl-2 expression increased 10.39 times (OR = 10.39; 95% CI = 2.73-39.56; p = 0.001)the risk of PROM . Conclusion High caspase-3 and AIF expressions and low Bcl-2 expression were risk factors for term PROM. Caspase-dependent and independent pathways of apoptosis were involved in the mechanism of PROM in term pregnancy.

Impact of human papilloma virus vaccination on adolescent knowledge, perception of sexual risk and need for safer sexual behaviors in Bali, Indonesia.

AIM: To determine the impact of human papilloma virus (HPV) vaccination on knowledge, perception of sexual risk and need for continued safe sexual behavior among Indonesian girls. METHODS: A comparative cross-sectional study was carried on in Denpasar, the capital city of Bali, Indonesia, during September 2015-February 2016. A total of 828 adolescent girls (12-16 years) were recruited to assess their knowledge on HPV/HPV vaccine, perception of sexual risks and need for continued safe sexual behavior. RESULTS: A total of 419 girls (50.7%) had received HPV vaccination prior to the study, 76.4% of whom (320/419) had sufficient knowledge about HPV. HPV vaccination was a strong and independent predictor of higher HPV/HPV vaccine knowledge (adjusted OR [AOR], 9.358; 95%CI: 6.816-12.849, P < 0.001). HPV vaccination (AOR, 0.107; 95%CI: 0.074-0.155, P < 0.001) and higher knowledge level (AOR, 0.667; 95%CI: 0.464-0.958, P = 0.028) were associated with lower perceived HPV risk. Despite the low risk perception, most of the vaccinated girls (408/419, 97.4%) continued to perceive higher need for safe sexual behaviors. On multivariate analysis, higher knowledge was the independent predictor for higher perceived need for safe sexual behaviors (AOR, 4.260; 95%CI: 2.016-9.001, P < 0.001). CONCLUSION: The HPV vaccination was associated with higher knowledge and appropriately lower perception of HPV risk. Despite the vaccination, most of the adolescents continued to perceive a need for safer sexual behavior. All adolescent girls should receive HPV vaccination in order to reduce cervical cancer burden in the future.

Combined panel of serum human tissue kallikreins and CA-125 for the detection of epithelial ovarian cancer / 부인종양

OBJECTIVE: To determine the predictive accuracy of the combined panels of serum human tissue kallikreins (hKs) and CA-125 for the detection of epithelial ovarian cancer. METHODS: Serum specimens collected from 5 Indonesian centers and 1 Vietnamese center were analyzed for CA-125, hK6, and hK10 levels. A total of 375 specimens from patients presenting with ovarian tumors, which include 156 benign cysts, 172 epithelial ovarian cancers (stage I/II, n=72; stage III/IV, n=100), 36 germ cell tumors and 11 borderline tumors, were included in the study analysis. Receiver operating characteristic analysis were performed to determine the cutoffs for age, CA-125, hK6, and hK10. Sensitivity, specificity, negative, and positive predictive values were determined for various combinations of the biomarkers. RESULTS: The levels of hK6 and hK10 were significantly elevated in ovarian cancer cases compared to benign cysts. Combination of 3 markers, age/CA-125/hk6 or CA-125/hk6/hk10, showed improved specificity (100%) and positive predictive value (100%) for prediction of ovarian cancer, when compared to the performance of single markers having 80-92% specificity and 74-87% positive predictive value. Four-marker combination, age/CA-125/hK6/hK10 also showed 100% specificity and 100% positive predictive value, although it demonstrated low sensitivity (11.9%) and negative predictive value (52.8%). CONCLUSION: The combination of human tissue kallikreins and CA-125 showed potential for improving prediction of epithelial ovarian cancer in patients presenting with ovarian tumors.