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Epithelial ovarian cancer (EOC) is a serious gynecological issue worldwide and its late detection is the major encumbrance in treatment procedures. Hypermethylation-mediated BRCA1 gene silencing results in failure of the repair system of damaged DNA playing an important role in ovarian carcinogenesis. BRCA1 gene hypermethylation can serve as a safe and highly specific clinical marker for EOC.The present study was conducted to evaluate the promoter hypermethylation of BRCA1 gene in EOC patients.This hospital-based case-control study carried out in the tertiary care hospital in New Delhi. Subjects and Methods: Promoter hypermethylation of BRCA1 gene was examined in 30 EOC diagnosed untreated cases confirmed by histopathological examinations and compared with 30 normal healthy controls matched for age using methylation specific-polymerase chain reaction.We found significantly higher BRCA1 promoter hypermethylation in the serum of EOC cases as compared to controls with P0.0001. BRCA1 gene methylation was found to have 70% sensitivity for the diagnosis of EOC with 100% specificity. A significant difference was observed in the range of CA125 levels, B12 and Folate levels between EOC cases and controls.We conclude that BRCA1 gene is significantly hypermethylated in EOC patients and thus can prove to be a noninvasive diagnostic tool. Our results provide prefatory evidence that epithelial ovarian epigenome can be influenced by dietary nutrients.

Genetic and epigenetic anomalies accountable for genetic dysregulation are the most common aberrations that determine the underlying heterogeneity of the tumor cells. Currently, phosphatase and tensin homolog (PTEN) incongruity has emerged as potent and persuasive malfunctioning in varied human malignancies. In this study, we have analysed the promoter hypermethylation and expression status of PTEN. We identified different mutations in the exonic region of PTEN. Functional consequences of these mutations were explored using in silico techniques. Promoter hypermethylation of PTEN was detected using methylation-specific polymerase chain reaction (MS-PCR), expression analysis was performed with immunohistochemistry (IHC) and mutation by direct sequencing in a total of 168 uterine cervix tumor cases. The findings were statistically correlated with the clinical parameters. In addition, the effect of nonsynonymous mutations was studied with molecular dynamics simulations. PTEN promoter hypermethylation (45.8%) was found to be significantly associated with the of PTEN loss (57.14%, P

In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter −248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk. This study aimed at exploring the association of BAX promoter −248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene–gene interaction of these two polymorphisms with risk of developing EOC. The study was conducted on 70 Epithelial ovarian cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated. We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23–13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40–13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13–4.86). The gene–gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95 % CI = 1.66–45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01). The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.

The recent investigation on PARK-2, a putative tumor suppressor gene, has found that it has been altered in multiple human malignancies. However, the clinical impact of PARK-2 alteration in uterine cervix carcinoma has not yet been studied. Therefore, we aimed to examine mutations, promoter hypermethylation, and protein expression of PARK-2 among the North Indian patients and their association with clinical parameters to evaluate the implication of PARK-2 in the genesis of cervical cancer. A total of 168 patient samples were processed for mutational analysis by single-strand conformation polymorphism, sequencing, and further in silico analysis of the identified mutations. Promoter hypermethylation by methylation-specific polymerase chain reaction and expression of PARK-2 were performed using immunohistochemistry. Statistical correlation between molecular findings and the clinicopathological parameters was taken to figure out the meaningful outcome. As per our findings, 3.5% (6/168) tumors showed novel missense mutations in exon 11 of PARK-2. In silico analysis showed high structural deviations manifested by mutations, A398D and Y391N, in both mutant proteins as compared to wild type. Promoter hypermethylation was observed in total of 29% of (48/168) tumor samples. Furthermore, 46.43% tumors (78/168) exhibited loss of PARK-2 expression in cervical carcinoma. The loss of expression of PARK-2 when correlated with clinical parameters resulted in significant association with tumor stage (p = 0.002) and with histological grade (p = 0.025). However, only clinical stage remained significant after Bonferroni correction (p0.007). A trend was observed between PARK-2 promoter hypermethylation and its protein expression. Our study provided sufficient information and insight for investigation of PARK-2 and highlighted its role as a tumor suppressor gene in cervical cancer in North Indian population.

Background: Unsatisfactory colposcopy, an inability to visualize the entire transformation zone, is found in about 10-20% of the patients undergoing the procedure. These patients usually require conization for a comprehensive evaluation of the cervix. Our study aims to compare the efficacy and safety of vaginal misoprostol versus vaginal estradiol in overcoming unsatisfactory colposcopy. Methods: We studied 48 women with unsatisfactory colposcopy. They were randomized into two groups: group I (n = 24) received 200 µg misoprostol vaginally and colposcopy was repeated after 6 h, while the subjects in group II (n = 24) were prescribed a 7-day course of 50 µg estradiol for vaginal insertion followed by a repeat colposcopy. The efficacy and safety of these two drugs were compared. Results: Repeat colposcopy was satisfactory in 70.8% of the women given vaginal misoprostol compared to 82.6% of the women who used vaginal estradiol. The difference was not statistically significant. The adverse effects were reported more often by the women in the misoprostol group (41.6%) as compared to those in estradiol group (13%) (p = 0.04). Conclusion: Both estradiol and misoprostol were comparable in overcoming unsatisfactory colposcopy. However, a higher incidence of adverse effects was noted with misoprostol as compared to estradiol.

MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p

Epithelial ovarian cancer (EOC) is the most lethal cause of morbidity and mortality worldwide. miRNA deregulation evinces a remarkable role in ovarian cancer tumorigenesis. miRNA-199a (miR-199a) is known to be involved in cancer development and progression. Although miR-199a has been studied in various cell types, its correlation with clinicopathological features in EOC has not been documented. In this study, we identified the clinicopathological hallmarks which might be perturbed due to the downregulation of serum miR-199a in EOC. Seventy serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-199a was detected by using miRNA qRT-PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Level of miR-199a expression was compared with distinct clinicopathological features. Expression of miR-199a was found to be significantly downregulated in comparison with matched normal controls. The expression level of miR-199a was found to be significantly associated with tumor stage, lymph node metastasis, and distal metastasis. Receiver operating characteristic (ROC) curve for diagnostic potential yielded significant area under the curve (AUC) with a considerable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status, and survival. Our findings suggest that miR-199a downregulation might be a potential indicator for disease progression promoting the aggressive tumor progression and be identified as a diagnostic marker to predict the prognosis and survival in EOC patients.

Cervical cancer is a major cause of morbidity and mortality particularly in developing countries. Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is associated with increased sensitivity to tyrosine kinase inhibitors (TKIs). In this study, the presence of EGFR mutations in cervical cancer and its correlation with HPV were identified. EGFR mutations were found in 31 out of 95 patients (32.63 %). Results showed the presence of EGFR mutations in 5.263 % of patients in exon 19. In exon 20, mutations were predominant in 25.26 % patients. While in exon 21, 8.421 % of patients had mutations. HPV, which is associated with cervical cancer development, was found in 95.78 % (HPVL1), 92.63 % (HPV16), and 3.15 % (HPV18) of patients. No correlation was found between HPV16 and EGFR mutations (p = 0.0616). Overall, mutations like V742R, Q787Q, Q849H, E866E, T854A, L858R, E872Q, and E688Q were found. Next, impact of TKI inhibitor (gefitinib) was checked with respect to presence or absence of mutation considering Q787Q mutation in exon 20 (G/A genotype) which is present in 25.2 % patients. Mutated cervical cancer cell lines showed higher sensitivity to gefitinib. Overall, this study suggests the importance of mutations in EGFR gene and indicates their relevance with respect to TKIs treatment in Indian cervical cancer patients.

Vitamin D deficiency is reported to be involved in pathogenesis of ovarian cancer. But the mechanism is yet to be explored. An imbalance between Th1 and Th2 activity play a crucial role in pathogenesis of many cancers. The purpose of the study is to find out the Th1/Th2 status by estimating TNF-α (Th1 marker) and IL-4 (Th2 marker) in ovarian cancer cases and controls and to correlate these with serum vitamin D levels.A case-control study with 50 ovarian cancer cases and 50 healthy controls was conducted. The cytokines TNF-α and IL-4 were estimated by ELISA. Serum vitamin D was measured by electro-chemiluminescence immunoassay method.Median TNF-α levels (12.2 vs 6.2 pg/ml; p value0.001) were significantly higher in ovarian cancer patients and mean IL-4 levels (2.22 ± 0.51 vs 2.99 ± 0.68 pg/ml; p value0.05) were significantly lower as compared to those of controls. Levels of TNF-α and IL-4 did not vary significantly with clinical staging, and histological grading. Vitamin D levels were negatively correlated with TNF-α and positively correlated with IL-4.Low vitamin D levels promotes Th1 activity increasing TNF-α levels and inhibits Th2 activity decreasing IL-4 levels in ovarian cancer. These low levels of vitamin D may induce pro-inflammatory micro ambience which might contribute to pathogenesis of ovarian cancer.

Objectives:To compare the sensitivity, specificity, positive and negative predictive values, and accuracy of Papanicolaou test with visual inspection with acetic acid (VIA)/VIA using magnification devices (VIAM) and develop the best strategy for screening in low resource settings.Materials and Methods:This is a prospective cross-sectional study on 408 symptomatic multiparous women in the reproductive age group, sequentially using the Papanicolaou test, the VIA, and the VIAM for screening. Women with a positive screening test underwent guided biopsy and endocervical curettage. The site of biopsy was recorded. Histopathological findings were taken as the "gold" standard in comparing the methods.Results:The mean (SD) age was 32.3 (6.8) years (range, 15-49 years), whereas the mean (SD) parity was 2.9 (1.2) (range, 1-9). Abnormal cytological findings were detected in 2.9% patients, whereas the remaining smears were negative for any intraepithelial lesion or malignancy. A total of 113 cases were screened positive by one/all methods. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Papanicolaou test, the VIA, and the VIAM were 24, 98, 42, 96, and 94%; 95, 78, 19, 99, and 79%; and 95, 78, 19, 99, and 79%, respectively, for high-grade lesions.Conclusions:The Papanicolaou test had low sensitivity but high specificity, whereas visual detection methods had a high sensitivity in addition to being cheaper. Alternative methods of screening such as VIA/VIAM can be a valuable alternative to the Papanicolaou test for cervical cancer screening in low resource settings. Visual inspection using magnification devices may be of benefit over VIA in doubtful cases.

To compare the sensitivity, specificity, positive and negative predictive values and accuracy of visual inspection with acetic acid under magnification (VIAM) and colposcopy for detecting cervical intraepithelial neoplasia (CIN) to determine if VIAM can substitute colposcopy in identifying the biopsy site in screen-positive cases. A prospective cross-sectional study was carried out on 408 symptomatic multiparous women in the reproductive age group (15–49 years) at a tertiary care teaching hospital. VIAM and colposcopy were used to screen for cervical precancerous lesions. Screen-positive women underwent guided biopsy and endocervical curettage. The site of biopsy was recorded as VIAM guided or colposcopy guided. Histopathology was taken as the gold standard. The mean age was 32.3 ± 6.8 years (range 15–49), whilst the mean parity was 2.9 ± 1.2 (range 1–9). A total of 113 women screened positive. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of VIAM and colposcopy were 95, 78, 19, 99 and 79%, and 86, 79, 18, 99 and 79%, respectively for high-grade lesions. VIAM can be a useful alternative to colposcopy when the latter is not available, as it has better sensitivity and equivalent specificity for detecting high-grade CIN.

Objective: Evaluation of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. Methods: In this prospective study, 400 women were screened using the Papanicolaou (PAP) smear, VIA and colposcopy. Those who had positive results with any of the screening methods underwent large loop excision of the transformation zone (LLETZ). The sensitivity and specificity of each of the screening methods was analyzed. Results: The sensitivity of VIA (96.7%) was much higher than that of the Pap smear (50%), and almost as high as that of colposcopy (100%). The specificity of VIA (36.4%) was lower than that of the Pap smear (97%) and colposcopy (96.9%), resulting in high false-positive rates for VIA. Two cases of endocervical lesions were missed with VIA. Conclusion: Visual inspection of the cervix with acetic acid is very sensitive for ectocervical lesions. The advantages of the VIA method are its low cost and ease of use (it can be used by paramedical workers), its high sensitivity and its immediate results (it is possible to “see and treat” at the first visit). Its main limitation is a high rate of false-positive results, which may lead to overtreatment if a “see and treat” policy is applied.

702 mothers were randomly selected and interviewed in a prospective study on maternal attitudes and trends in initiation of newborn feeding in Lady Hardinge Medical College, New Delhi, India. Information was obtained regarding type and time of 1st feed, feeding method, inclination and knowledge about breastfeeding, source of advice, practices of discarding colostrum, and incidence of lactation failure and noted in a pretested proforma. 305 of the mothers were primipara and 297 multipara. Approximately 83.5% of the mothers had visited the antenatal clinics, but only 13.4% had been given breastfeeding advice at these clinics. 95.01% of the mothers indicated inclinations about breastfeeding. 47.37% of the mothers who knew about breastfeeding had been instructed by the doctors at some stage. Nurses were responsible for imparting knowledge about breastfeeding only in 0.59% mothers. In terms of the type of 1st feed, no significant difference was observed according to parity. Honey, which has been used traditionally as a 1st feed, was given in 26.78% of the babies. The next popular feed other than breastfeeding was plain water, which was given in 21.36% of babies. 12.53% of babies were fed glucose in water. Only 26.35% initiated feeding with breast milk; only 16.9% had been given colostrum. 1st feed was given through a spoon in 28.91% babies; 19.37% and 4.13% were fed via the fingertips and cotton, respectively, after dipping into the foodstuff. The time of 1st breastfeed also varied widely. Most of the mothers fed the babies within 24 hours, but around 30.31% mothers breastfed the babies only after 24 hours. Most mothers fed their babies on demand. Despite the willingness to breastfeed, 58.32% mothers could not identify even 1 advantage of breastfeeding. A significantly higher percentage of primiparous mothers were ignorant about advantages of breastfeeding as compared to multiparous parents -- 71.73% versus 48.84%. 15.74% mothers intended to breast feed until the infant was 6 months; 49.52% planned to stop breastfeeding after 12 months. 3.13% of the mothers experienced lactation failure. Clearly, better health education is called for regarding the early initiation of breastfeeding and the importance of colostrum to newborn and weaning practices.