Normal Cervix Research Articles

Correlation between Methylation of SALL3 and Cervical Cancer

Objective To detect the methylation status of SALL3 gene promoter region in normal cervical tissues,cervical cancer tissues,and cervical cancer cell lines and thus explore the relationship between methylation status and the expression of SALL3 gene.Methods The DNA methylation statuses of SALL3 gene in normal cervical,cervical cancer tissues and cervical cancer cell lines were analyzed by methylation-specific PCR(MS-PCR).The expressions of SALL3 mRNA in cervical cancer cell lines,cervical cancer tissues,and normal cervical tissues were detected by RT-PCR.Results In cervical cancer and matched peri-carcinomatous samples,the methylation levels of SALL3 were up-regulated(CCa vs.CCap:P=0.046;CCa vs.NC P=0.039)and the protein expressions were down-regulated(CCa vs.CCap:P=0.012;CCa vs.NC P=0.000)when compared with normal cervix samples.The mRNA levels of SALL3 in HeLa and SiHa cells treated with 5-Azacytidine were elevated in a dose-dependent manner(HeLa:P=0.001;SiHa:P=0.002).The methylation level of SALL3 was higher in high risk human papillomavirus(HPV)-positive cervical samples than in HPV-negative cervical samples(P=0.014),which also resulted in a descending SALL3 expression in HPV-positive samples(P=0.021).Conclusions The hypermethylation of SALL3 in promoter regions inhibits the expression of SALL3 in cervical cancer tissue samples.Infection with high-risk HPV serotypes may increase the methylation of SALL3 promoter region,silence its expression,and thus promote the development of cervical cancer.

Papillary squamotransitional cell carcinoma of the uterine cervix: a case report and review of the literature

BackgroundPapillary squamotransitional cell carcinoma of the uterine cervix is a rare neoplasm, a subtype of transitional cervical carcinoma that appears to be a variation of squamous cervical carcinoma. It has a disposition toward metastasis at an advanced stage and local recurrence. Owing to the difficulty of illustrating the invasion histologically, misdiagnosis is likely to affect the patient’s prognosis.Case presentationWe present a case report of an 81-year-old Caucasian patient with squamotransitional cell carcinoma with unusual clinical behavior that was primarily thought to be ovarian cancer. According to the clinical examination and radiologic imaging, the patient had no vaginal bleeding and a normal cervix. Nevertheless, the tumor was already metastasized at the retroperitoneal tissue and at the right ovary. Computed tomography-guided biopsy of the right adnexa gave no further clarification. Although the tumor resembled urothelial cancer, this diagnosis was dismissed because of the results of immunohistochemistry analysis with CK7+, CK5+, and CK20−. Because of the differential diagnosis of ovarian cancer, we decided in favor of an exploratory surgical approach. Hysterectomy with bilateral adnexectomy, extensive retroperitoneal tumor debulking, and infragastric omentectomy was performed by laparotomy. Histopathology revealed a squamotransitional cervical cancer as the primary tumor with a tumor stage of pT3b, pN1 (1/2), V0, RX, G2, corresponding to International Federation of Gynecology and Obstetrics stage IIIB.ConclusionsAs far as we are aware, this is the first report of papillary squamotransitional cell carcinoma of the uterine cervix metastatic to the ovary without vaginal bleeding and with a clinically and radiologically unsuspicious cervix. Physicians should always contemplate papillary squamotransitional cell carcinoma of the uterine cervix in unclear cases with ovarian metastasis, especially if the histology indicates a transitional cancer (CK7+ and CK20−), before proceeding with treatment. More cases are needed to illuminate the clinical characteristics and categorization of papillary squamotransitional cell carcinoma of the uterine cervix.

Hysteroscopic Resection of a Complete Uterine and Vaginal Septum Under Laparoscopic Ultrasound Guidance

Video Objective The aim of this video is to demonstrate the use of laparoscopic ultrasound guidance during hysteroscopic resection of a congenital uterine and vaginal septum. Setting Our patient is a 20 year old G0 female who presented for difficulty with tampon insertion and removal as well as painful intercourse. On physical exam, the patient was noted to have a complete, non-obstructing longitudinal vaginal septum with two separate normal cervices. MRI of the abdomen and pelvis showed a complete septate uterus, two cervices, and two normal kidneys. Interventions This video shows the simultaneous use of hysteroscopy and laparoscopic ultrasound to safely and successfully resect the uterine and vaginal septum. Conclusion The goal is to encourage use of this technique during similar procedures for patients with mullerian duct anomalies desiring surgical correction.

Apparent Diffusion Coefficient Value Changes of Normal Uterine Cervix with Aging

Background: In the magnetic resonance imaging (MRI) of many tissues, apparent diffusion coefficient (ADC) values vary with age. In the literature, there are no studies in which normal cervix ADC values and their relationship with age is analyzed. Objectives: To evaluate whether changes occur in ADC values with aging in the uterine cervix with 3-Tesla MRI. Patients and Methods: Female patients aged between 18 and 70 years who were found to have lower abdominal diffusion-weighted magnetic resonance imaging (DWI) in the radiology database from December 2017 to May 2018 were evaluated. All DWI examinations were performed using a 3-T MR with 2 b values (b = 50, 800 s/mm2). A total of 161 patients were divided into two groups according to their menopausal status (premenopausal n = 106, postmenopausal n = 55). To evaluate the correlation between the age of the patient and the ADC values, Pearson correlation analysis was performed. Results: The mean age of the patients was 41.4 ± 11.6 years. The mean ADC value was 1.276 ± 0.25 mm2/sec × 10-3 in the whole population. There was a negative correlation between age and ADC values. The mean cervix ADC value of premenopausal and postmenopausal patients was 1.333 ± 0.23 mm2/sec × 10-3 and 1.165 ± 0.25 mm2/sec × 10-3, respectively. There was a statistically significant difference between the groups in term of cervix ADC value (P < 0.05). Conclusion: A negative correlation between aging and ADC values was found. Menopausal status has an effect on the ADC values of the cervix. These findings may indicate cellular and extracellular matrix changes in the cervix tissue with aging and menopausal status.

α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer.

Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.

Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development.

Objective:Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated cervical carcinogenesis. Methodology: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC. Results: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010). Conclusion:The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.

Prediction of time of delivery using cervical length measurement in women with threatened preterm labor

Objective To evaluate the use of transvaginal (TV) sonographic cervical length (CL) measurement alone in predicting time of delivery in women who present in threatened preterm labor. Methods A retrospective cohort study at Royal Brisbane and Women’s Hospital of all women who presented between 22 weeks and 0 days and 35 weeks and six-day gestation in threatened preterm labor and were admitted for ongoing management including a TV sonographic CL measure. The accuracy of CL for predicting time of delivery was compared between women with a short cervix (CL < 25 mm) and those with a normal cervix (CL ≥25 mm). The predictive accuracy of CL for spontaneous preterm delivery was analyzed with different outcome-specific thresholds. Results One hundred and forty-six women with threatened preterm labor met the inclusion criteria; of which 74 (50.7%) had a short cervix and 72 (49.3%) had a normal cervix. The group with short cervix were more likely to deliver prematurely before 37-week gestation, as well as a shorter time interval between initial presentation and delivery and delivery within 14 days from presentation (p = .0002, p = .0001, and p = .0001, respectively). Similarly, with respect to the area under the receiver operator characteristic curves, CL measurement was found to be significant for time of delivery before or after 37 weeks (p < .0001), preterm delivery before 34 (p = .0003) and 31 (p < .0001) weeks; and preterm delivery within 14 days from presentation (p < .0001). Cervical length measurement has a high negative predictive value ranging from 94.9 to 97.1% depending on the different CL threshold used. Conclusions Cervical length measurement at the time of presentation was significantly associated with the risk of preterm delivery in women presenting with threatened preterm labor and a short cervix. Cervical length measurement was also helpful in predicting time of delivery within 14 days from presentation. The negative predictive value and predictive accuracy of CL as a single measure were of significance.

On the potential use of dynamic contrast-enhanced (DCE) MRI parameters as radiomic features of cervical cancer.

To evaluate whether the analysis of high-temporal resolution DCE-MRI by various tracer kinetic models could yield useful radiomic features in discriminating cervix carcinoma and normal cervix tissue. Forty-three patients (median age 51yr; range 26-78yr) diagnosed with cervical cancer based on postoperative pathology were enrolled in this study with informed consent. DCE-MRI data with temporal resolution of 2s were acquired and analyzed using the Tofts (TOFTS), extended Tofts (EXTOFTS), conventional two-compartment (CC), adiabatic tissue homogeneity (ATH), and distributed parameter (DP) models. Ability of all kinetic parameters in distinguishing tumor from normal tissue was assessed using Mann-Whitney U test and receiver operating characteristic (ROC) curves. Repeatability of parameter estimates due to sampling of arterial input functions (AIFs) was also studied using intraclass correlation (ICC) analysis. Fractional extravascular, extracellular volume (Ve) of all models were significantly smaller in cervix carcinoma than normal cervix tissue, and were associated with large values of area under ROC curve (AUC 0.884-0.961). Capillary permeability PS derived from the ATH, CC, and DP models also yielded large AUC values (0.730, 0.860, and 0.797). Transfer constant Ktrans derived from TOFTS and EXTOFTS models yielded smaller AUC (0.587 and 0.701). Repeatability of parameters derived from all models was robust to AIF sampling, with ICC coefficients typically larger than 0.80. With the use of high-temporal resolution DCE-MRI, all tracer kinetic models could reflect pathophysiological differences between cervix carcinoma and normal tissue (with significant differences in Ve and PS) and potentially yield radiomic features with diagnostic value.

Prevalence of Cervical Intra Epithelial Neoplasia (CIN) among the sexually active married Women at Rajshahi Division

Background: Cervical cancer is 4th most common cancer in women in the world and the most common form of cancer in women in developing countries. Population based cervical cancer screening and treatment of intraepitheial neoplasia in early stage can reduce morbidity and mortality associated with cervical cancer. To determine the prevalence of cervical intra epithelial neoplasia (CIN) among sexually active and married women in Rajshahi Division of Bangladesh.&#x0D; Place and Duration: This population based cross sectional study was carried out in 4 selected Upazilla from 4 different districts of Rajshahi Division from 1st December 2014 to 31st May 2015. Study on 1050 sexually active women between 25 to 55 years of age who fulfilled the inclusion criteria enrolled in the study after taking the consent.&#x0D; Result: Among 1050 enrolled women 90 (8.5%) were VIA positive and 91 were colposcopically abnormal and among them 33 were CIN positive &amp; 58 had chronic cervictis with or without squamorus metaplasia. Mean age of CIN positive women was 36.75 years, 92.2% were housewife &amp; 7.8% were service holder and in 64.6% women education level was up to XII class. In fifty five percent of their husband was day labouer from poor socioeconomic condition.&#x0D; Conclusion: VIA and Colopscopy can differentiate a normal cervix from a precancerous cervix with reasonable accuracy. Till now a good number of studies had been carried out in different countries of world and it is now well established that sensitivity of the test is very good. From the present study we can conclude that it will give a very good information about the prevalence of CIN in our country and by proper management of the CIN cases the incidence of carcinoma cervix can be reduced.&#x0D; Bangladesh J Obstet Gynaecol, 2018; Vol. 33(1) : 17-20

NSD2 inhibition suppresses metastasis in cervical cancer by promoting TGF-β/TGF-βRI/SMADs signaling

The molecular mechanisms revealing cervical cancer progression remain unclear. NSD2 belongs to the NSD family of histone lysine methyltransferases (HMTases), and is a histone methyltransferase that regulates dimethylation of histone 3 lysine 36 (H3K36me2). In this study, we explored the effects of NSD2 on the tumorigenesis and metastasis in cervical cancer. We found that NSD2 exhibited a pattern of gradual up-regulation from normal cervix (NC) to cervical carcinoma in situ (CIS) and then to invasive cervical cancer (ICC). NSD2 knockdown markedly reduced the cervical cancer cell proliferation. Loss of function assay in vitro suggested that NSD2 deletion markedly prevented the cervical cancer cell migration and invasion. Consistently, the in vivo results demonstrated that NSD2 knockdown not only reduced tumor growth, but also prevented the development of tumor metastasis. In addition, NSD2 knockdown clearly reduced the expression levels of transforming growth factor-β1 (TGF-β1), TGF-βRI, phosphorylated SMAD2 and SMAD3 in cervical cancer cells, accompanied with the decreased expression of genes that promoted tumor metastasis. Importantly, we found that NSD2 knockdown-regulated expression levels of metastasis-associated genes were reversed by TGF-β1 incubation. Therefore, our findings demonstrated that NSD2-modulated activation of TGF-β1/TGF-βRI/SMADs signaling pathway was crucial for cervical cancer progression, which might be a promising therapeutic strategy to overcome metastasis in cervical cancer.

Infiltrating CD4 and CD8 lymphocytes in HPV infected uterine cervical milieu.

PurposeTumor infiltrating lymphocytes (TILs) have been extensively described in anti-tumor immunity, but their functional alterations in the immunoediting processes during neoplastic progression in the uterine cervix are still not clear. Our aim was to gain insight into cervical tissue T cell populations, determine if there are any differences in the localization and quantity distribution of T lymphocytes, and to evaluate their role in disease regression or progression in the cervical neoplastic milieu.Patients and methodsSerial section analysis of immunohistochemically stained CD4 and CD8 lymphocytes was performed on a total number of 72 samples, categorized into four cohorts: 23 HPV non-infected (HPV-) normal cervix, 20 HPV infected (HPV+) normal cervix, 17 HPV+ low grade cervical intraepithelial neoplasia (CIN), and 12 HPV+ high grade CIN.ResultsLow infiltrating lymphocytes (ILs) in normal cervix and high ILs in CIN were observed, while the trend of ILs increased with increasing grade of CIN, which was statistically significant (P<0.0001). Quantitative and localization analysis between the subsets of T cells showed that, in the epithelial layer, infiltrating CD8+ lymphocytes (CD8+ILs) were significantly higher than CD4+ILs in HPV+ normal cervix, while the trend decreased with increasing grade of CIN (P=0.011). Whereas, in the stromal layer, CD4+ILs were predominant in all study groups and no statistical difference was found between these groups. However, tumor infiltrating CD8+ lymphocytes (CD8+TILs) were noted to be significantly higher than CD4+TILs in severe dysplastic cases.ConclusionT cell infiltrates were predominant as the grade of the lesion progressed into more advanced lesions, which likely represent the lesions that have persisted over time. The variation in the infiltration rate and the location of CD4+ILs and CD8ILs may suggest the efficacious role of CD8 T cells in eliminating HPV infected cervical epithelial cells and also provides insight into the complex role of TILs in facilitating and mediating sustained anti-tumor responses, hence preventing tumor outgrowth.

The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer.

BackgroundIt is unclear whether low density lipoprotein receptor-related protein 11 (LRP11), a newly found lipoprotein receptor regulatory protein, has the carcinogenic effects in cervical cancer.MethodsBioinformatics analysis, immunohistochemical (IHC) staining and evaluation, cell proliferation assay, flow cytometry, transwell migration and invasion assays, Western blotting, growth of LRP11-silenced cells in athymic nude mice were performed in this research.ResultsWe found that LRP11 expression was higher in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissue than in normal cervix, and high expression of LRP11 was associated with differentiation degree (P=0.0266), indicating poor prognosis (P=0.0210). The silencing of LRP11 in SiHa and CaSki cell lines inhibited cell proliferation, reduced migration and invasion and suppressed cell growth in nude mice, which possibly related to cell cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF. Furthermore, LRP11 showed substantial positive correlation with P16 in vivo and in vitro.ConclusionLRP11 plays important roles in proliferation, migration and invasion, with the potential to be a useful prognostic marker and therapeutic target for patients with HSIL and cervical cancer.

Relationship between cervical lesions and the type-specific viral load of high risk HPV reflected by the Ct value of Cobas 4800 HPV system

Objective: To explore the relationship between cervical lesions and high risk HPV (HR-HPV) viral load reflected by the cycle threshold (Ct) values of Cobas 4800 HPV (Cobas 4800) system. Methods: From August 2016 to September 2017, 7 000 women from Shenzhen, were recruited for cervical cancer screening with Cobas 4800 system and cytology co-test. Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16,18 with cytology [≥ atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥ low grade squamous intraepithelial lesion (LSIL)]. The Ct values of HPV 16, 18 and all combined other types coming from Cobas 4800 system were used as an indicator of viral load to analyze the relationship between type-specific HPV load and the cervical lesions. Results: (1) Among the 7 000 screening women, 370 cases were positive for cervical cancer screening, 325 of them underwent colposcope biopsies, and coloposcopy referred rate was 87.8% (325/370). Among 325 women undergoing cervical biopsy, pathological diagnosis was 119 cases of normal cervical cervix, 151 cases of LSIL, and 55 cases of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL(+); including 53 cases of HSIL, 1 case of cervical adenocarcinoma, and 1 case of cervical squamous cell carcinoma). (2) The Ct value of HPV 16 was inversely correlated with the upgrading of the lesions (r=-0.617, P=0.000), and significant different among normal cervix,LSIL and HSIL(+) (35.4±4.5 vs 31.0±6.0 vs 26.5±4.0; F=25.537, P=0.000). There was no correlation between Ct value of HPV 18 and cervical lesions (r=-0.021, P=0.902). The Ct value of other 12 HPV types was statistically difference among normal normal cervix, HSIL(+) and cervicitis (33.0±5.3 vs 29.9±7.2 vs 29.8±5.8; F=5.087, P=0.007). Among them, LSIL and HSIL(+) were significantly lower than normal cervix (P<0.05), but there was no significant difference between LSIL and HSIL(+) (P>0.05). Conclusion: The Ct value of HPV 16 detecting in Cobas 4800 system as an indicator of virus load obviously correlates with different grades of cervical lesions, therefore could be a reference of cervical lesion existence and an indicator of lesion prognosis.

Application of Saline Infusion Sonocolpography in Diagnosis and Treatment of Perforated Transverse Vaginal Septum

Transverse vaginal septum (TVS) is a particularly rare vaginal anomaly, and diagnosis is often difficult in a genital examination. We herein present a case of perforated TVS for which successful diagnosis and treatment were achieved using a new technique referred to as saline infusion sonocolpography. A 32-year-old female presented with primary infertility. Speculum examination revealed a blind vaginal canal with two pinpoint perforating holes. Foley catheters with inflated balloon were inserted into the two apertures, and then normal saline was injected through the catheters to distend the vaginal pouch. This procedure of saline infusion sonocolpography revealed the uterine cervix and vaginal pouch and permitted diagnosis of perforated TVS of the upper vagina. The septum was excised and a normal cervix was ascertained. The patient had no complication such as agglutination of the vagina postoperatively. This case suggests that saline infusion sonocolpography may be useful for diagnosis and treatment of TVS.

Aberrant Nuclear Localization of aPKCλ/ι is Associated With Poorer Prognosis in Uterine Cervical Cancer.

We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, χ test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι localization differed between the intraepithelial lesion and adjacent invasive cancer in 40% of cases, while the expression pattern was similar between primary and matched metastatic tumors. In conclusion, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.

Síndrome de Herlyn-Werner-Wünderlich y diagnóstico tardío: a propósito de un caso

El síndrome de Herlyn-Werner-Wünderlich es una anomalía congénita del tracto urogenital. Se caracteriza por la tríada de útero didelfo, hemivagina obstruida y agenesia renal unilateral. La mayoría de pacientes se mantienen asintomáticas hasta la menarquia, cuando debutan con dismenorrea, dolor pélvico y masa palpable debido al hematocolpos asociado. Presentamos el caso de una paciente de 32 años en estudio por problemas de fertilidad. Se realizó estudio ecográfico 3D e histerosalpingografía, donde se observó útero bicorne completo con doble canal cervical, con impresión diagnóstica de vagina homolateral ciega. A la especuloscopia durante el periodo menstrual se observó cérvix de hemivagina normal y orificio de salida en cara lateral, por donde drenaba sangre de hemivagina ciega (probablemente fistulizada). Se realizó una ecografía abdominal que constató agenesia renal izquierda, confirmándose el diagnóstico.

Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes.

The exact molecular mechanisms underlying cervical tumorigenesis are poorly understood. Polycomb complex protein Bmi1 (Bmi1) is involved in the malignant transformation and biological aggressiveness of several human carcinomas. Therefore, the present study assessed the expression of Bmi1 protein in human cervical cancer tissues and examined the mechanisms involved in cervical carcinogenesis. The expression of Bmi1 protein was examined by immunohistochemistry in cervical carcinoma tissues (n=71), high-grade squamous intraepithelial lesions (n=41) and normal cervical tissues (n=47). Expression of Bmi1 protein gradually increased across samples from the normal cervix (1/47; 2.12%), high-grade squamous intraepithelial lesions (5/42; 16.13%) and cervical carcinomas (31/71; 43.66%; P<0.05). Additionally, Bmi1 protein expression was associated with tumor histopathological grade. The effects of Bmi1 silencing and overexpression on tumor sphere formation and the tumorigenicity of cervical cancer cells were investigated. Overexpression of Bmi1 resulted in significantly attenuated tumor formation and tumor sphere formation. Consistently, Bmi1 silencing significantly inhibited tumor formation and tumor sphere formation. Furthermore, Bmi1 upregulated the expression of Sox2, and the dual-luciferase reporter assay and chromatin immunoprecipitation showed that Bmi1 transactivated Sox2 by binding to the two E-box motifs in the Sox2 promoter. In conclusion, aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes as a potential oncogenic factor that participates in the carcinogenesis of cervical carcinomas.

Unicornuate uterus with a rudimentary non-communicating cavitary horn in association with VACTERL association: case report

BackgroundThe unicornuate uterus is caused by abnormal or failed development of one Müllerian duct. Unicornuate uteri with functioning non-communicating rudimentary horns are susceptible to many gynaecologic and obstetric complications such as hematometra, endometriosis and ectopic pregnancy and thus surgical resection is usually recommended..Case presentationWe report a rare case of a unicornuate right uterus with rudimentary non-communicating (functional) cavitary left horn (class U4a) in a 17-year-old girl who was diagnosed with VACTERL association. She was presented to our centre with 3 years history of secondary sever dysmenorrhea. Pelvic magnetic resonance imaging revealed a normal uterus on the right side, a 7 × 8 cm left endometrioma, a tortuous dilated fluid-filled structure in the left hemipelvis, mostly represented left-sided hematosalpinx, and a well-defined lesion with thick enhancing wall in the left hemipelvis measuring 6.7 × 5.7 × 5.6 cm with a similar enhancement to the uterus in the right. She underwent laparotomy that showed a right unicornuate uterus with a normal cervix and a rudimentary non-communicating distended left horn. In addition, there was a left endometrioma and left hematosalpinx. Resection of the left communicating horn, left salpingectomy and left ovarian cystectomy were performed. The right tube and both ovaries were preserved. At 9-months follow up, the patient had a regular period and the pain subsided completely.ConclusionWe report yet the second case of VACTERL association and unicornuate uterus with non-communicating functional rudimentary horn, in hope of expanding the knowledge of a rare occurrence. This case also highlights the importance of considering the diagnosis of Müllerian duct anomalies in patients with a history of other anomalies, and/or history of early-age secondary dysmenorrhea.

Prevalence of Cervical Intra Epithelial Neoplasia (CIN) among the Sexually Active Married Women by Colposcopy at Rajshahi Division

Objective: To determine the prevalence of cervical intra epithelial neoplasia (CIN) among sexually active married women in Rajshahi division of Bangladesh. Study Design: It is a prospective cross sectional type descriptive study.&#x0D; Place and Duration: This study is population based &amp; carried out in 4 selected Upazilla from 4 different districts of Rajshahi Division. Total 1050 patient were enrolled in the study. Study period was 6 months from 1st December 2014 to 31st May 2015. Subject and Method: All sexually active woman between age group 25 to 55 years in selected Upazilla. In UHC of preselected Upazilla who fulfilled the inclusion criteria enrolled in the study after taking the consent. Frequency &amp; risk factors for CIN were analyzed after entering in predesigned proforma.&#x0D; Result: During study period of 6 months among 1050 enrolled patients 90 patient were VIA positive and 91 patients were colposcopically abnormal and among these 33 patients were CIN positive &amp; 58 patients had chronic cervicitis with or without squamous metaplasia. Mean age of CIN positive were 36.75 years, 92.2% patient were housewife &amp; 7.8% patient were service holder and in 64.6% patients education level up to XII class, in 55.5% patients husband was day labour from poor socioeconomic condition.&#x0D; Conclusion: VIA and Colposcopy can differentiate a normal cervix from a precancerous cervix with reasonable accuracy. Till now, a good number of studies had been carried out in different countries of world &amp; it is now well established that sensitivity of the test is very good. From the present study we can conclude that it will give very good information about the prevalence of CIN in our country and by follow up study this might help us in reducing the incidence of carcinoma cervix.&#x0D; TAJ 2018; 31(2): 1-5

Octamer binding transcription factor-4 expression is associated with cervical cancer malignancy and histological differentiation: a systematic review and meta-analysis.

Objective: In this work, the relationship between octamer binding transcription factor 4 (OCT-4) expression and the clinicopathological features of cervical cancer (CC) is evaluated in detail.Methods: The library databases Pubmed, Embase, Cochrane library, Wan Fang and Chinese National Knowledge Infrastructure (CNKI) were searched for research related to these concepts published from the time the databases were established until May 2018. The obtained studies are screened, extracted, and evaluated according to the inclusion and exclusion criteria, and meta-analysis is carried out via RevMan 5.3.Results: Ten case–control studies, including 408 cases of CC, 164 cases of cervical intraepithelial neoplasia (CIN), and 148 cases of normal cervix, are included in the analysis. Results show that OCT-4 levels are statistically significantly different between the CC and normal cervical tissue groups (odds ratio (OR) = 15.59, 95% confidence interval (CI): 8.70, 27.94), the CC and CIN groups (OR = 5.64, 95% CI: 3.23, 9.86), the CIN and normal cervical tissues groups (OR = 7.13, 95% CI: 2.41, 21.05), and the CC well/moderately differentiated and poorly differentiated groups (OR = 0.44, 95% CI: 0.24, 0.81). OCT-4 is not statistically significantly different between CIN I + II and CIN III tissues (OR = 0.40, 95% CI: −0.02, 0.81), the CC lymphatic and non-lymphatic metastasis groups (OR = 1.93, 95% CI: 0.83, 4.47), the FIGO I and FIGO II groups (OR = 0.79, 95% CI: 0.29, 2.13), and the adenocarcinoma and squamous cell carcinoma groups (OR = 1.55, 95% CI: 0.70, 3.44).Conclusions: The available evidence suggests that OCT-4 expression is associated with CC malignancy and histological differentiation. This finding, however, is subject to quantitative studies and quality tests.