Incidence Of Cervical Adenocarcinoma Research Articles

Survival benefit of surgery with postoperative radiotherapy in locally advanced cervical adenocarcinoma: a population-based analysis

BackgroundThe incidence of cervical adenocarcinoma (AC) has experienced a considerable increase in recent decades. Despite this, our understanding of the optimal management of locally advanced cervical AC remains limited. The present study sought to compare the clinical outcomes of radical hysterectomy with postoperative radiotherapy (PORT) and primary radiotherapy (RT) in patients with locally advanced cervical AC using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsThe data were extracted from the SEER database utilizing the SEER ∗ STAT software (version 8.4.0.1). The study included patients diagnosed with locally advanced cervical AC between 2004 and 2017 with adequate information available for analysis. Patients were assigned to either the Surgery + PORT or Primary RT group based on treatment modality, and their clinical characteristics were compared. Propensity score matching (PSM) was utilized to adjust for differences in baseline characteristics between groups. The primary endpoints of the study were overall survival (OS) and cancer-specific survival (CSS).ResultsOf the 1363 patients who met the inclusion criteria, 302 (22.16%) underwent Surgery + PORT, while 1061 patients received Primary RT. The two groups differed significantly in terms of age, year of diagnosis, tumor size, grade, stage, T/N stage, and chemotherapy. PSM was performed to balance the baseline characteristics between the two groups, resulting in 594 patients being analyzed. After PSM, the Surgery + PORT group exhibited significantly improved survival rates. The 5-year OS rates were 69.7% (95% CI: 63.3%-76.9%) for the Surgery + PORT group and 60.9% (95% CI: 56.0%-66.3%) for the group receiving Primary RT (p = 0.002). The 5-year CSS rates for the two groups were 70.7% (95% CI: 64.3%-77.8%) and 66.2% (95% CI: 61.3%-71.5%), respectively (p = 0.049). Multivariate analysis revealed that Surgery + PORT was an independent favorable prognostic factor for OS (HR = 0.60, p = 0.001) and CSS (HR = 0.69, p = 0.022). Although the combined approach of surgery and PORT resulted in a favorable impact on OS in patients aged 65 years or older (HR = 0.57, p = 0.048), it did not result in a statistically significant improvement in CSS in the same age group (HR = 0.56, p = 0.087). Similarly, the combined treatment did not yield a statistically significant increase in either OS (HR = 0.78, p = 0.344) or CSS (HR = 0.89, p = 0.668) in patients with tumors larger than 60 mm.ConclusionThe present study demonstrated that Surgery + PORT was associated with improved OS and CSS in patients with locally advanced cervical AC when compared to Primary RT. As such, Surgery + PORT may be a preferable therapeutic option for carefully selected patients with cervical AC. These findings offer valuable insight into the management of locally advanced cervical AC and may assist in personalized treatment decisions.

A novel human papillomavirus and host DNA methylation score and detection of cervical adenocarcinoma.

The widespread introduction of Pap testing in the 1960s was followed by substantial reductions in the incidence of cervical squamous cell cancer (SCC). However, the incidence of cervical adenocarcinoma (ADC) did not decrease, likely because of low Pap test sensitivity for ADC and adenocarcinoma in situ (AIS). This study assessed a novel human papillomavirus (HPV) and host DNA Methylation Score for AIS and ADC screening. We measured methylation levels at CpG sites in the L2/L1 open reading frames of HPV16, HPV18, and HPV45-as well as 2 human loci, DCC and HS3ST2. Specifically, we tested exfoliated cervicovaginal cells from women in the HPV Persistence and Progression (PaP) cohort who were positive for 1 of HPV16, 18, or 45, including: 1) 176 withAIS/ADC, 2) 353 with cervical intraepithelial neoplasia-3 (CIN3) or SCC, and 3) controls who either cleared (HPV-Clearers; n = 579) or had persistent HPV16, 18, or 45 infection (HPV-Persisters; n = 292). CpG site-specific methylation percentages were measured using our reported next-generation methods. The Methylation Score was the average methylation percentage across all 35 CpG sites tested. Each individual CpG site had higher methylation percentages in exfoliated cervicovaginal cells collected from patients with AIS/ADC, and as well as those with CIN3/SCC, relative to either control group (weakest P = .004). The Methylation Score for AIS/ADC had a sensitivity of 74% and specificity of 89%. The multivariate odds ratio (OR) between the Methylation Score (4th vs 1st quartile) for AIS/ADC was ORq4-q1 = 49.01 (PBenjamini-Hochberg = 4.64E-12), using HPV-Clearers as controls. CIN3/SCC had similar, albeit weaker, associations with the Methylation Score. HPV16/18/45-infected women with Methylation Scores in the highest quartile had very high odds of AIS/ADC, suggesting they may warrant careful histologic evaluation of the cervical transition zone (eg, conization or loop electrosurgical excision procedure [LEEP]).

Insulin-induced gene 2 expression is associated with cervical adenocarcinoma malignant behavior.

The incidence of cervical adenocarcinoma (CA) as a malignant tumor has increased over the past few decades due to its low detection rate and malignant biological behaviors. Insulin-induced gene 2 (INSIG2), a membrane protein of the endoplasmic reticulum (ER), plays a crucial role in cancer progression. However, there is little known about the connection between INSIG2 and CA. The Human Protein Atlas (HPA) and the Cancer Genome Atlas (TCGA) Cervical Cancer (CESC) data were applied to study the alteration in INSIG2 expression. Biological functions were performed to test the change of malignant behavior. Bioinformatics analysis was conducted to explore the potential affection of INSIG2 in CA progression. Our study confirmed that the high INSIG2 expression levels had a poor prognosis. INSIG2-knockdown inhibited the CA cell proliferation, migration, and invasion of CA cells while downregulating the epithelial-mesenchymal transition (EMT)-associated gene expression levels. Moreover, the enrichment analysis of DEGs showed more potential functions of INSIG2 in the CA progression. We found that INSIG2 knockdown may play a suppressor role in the CA progression, and may provide the potential functional influence in inhibiting of CA development.

Evaluation of X-ray and carbon-ion beam irradiation with chemotherapy for the treatment of cervical adenocarcinoma cells in 2D and 3D cultures.

Cervical cancer is the second most common cancer in women and causes more than 250,000 deaths worldwide. Among these, the incidence of cervical adenocarcinomas is increasing. Cervical adenocarcinoma is not only difficult to detect and prevent in the early stages with screening, but it is also resistant to chemotherapy and radiotherapy, and its prognosis worsens significantly as the disease progresses. Furthermore, when recurrence or metastasis is observed, treatment options are limited and there is no curative treatment. Recently, heavy-particle radiotherapy has attracted attention owing to its high tumor control and minimal damage to normal tissues. In addition, heavy particle irradiation is effective for cancer stem cells and hypoxic regions, which are difficult to treat. In this study, we cultured cervical adenocarcinoma cell lines (HeLa and HCA-1) in two-dimensional (2D) or three-dimensional (3D) spheroid cultures and evaluated the effects of X-ray and carbon-ion (C-ion) beams. X-ray irradiation decreased the cell viability in a dose-dependent manner in 2D cultures, whereas this effect was attenuated in 3D spheroid cultures. In contrast, C-ion irradiation demonstrated the same antitumor effect in 3D spheroid cultures as in 2D cultures. In 3D spheroid cultures, X-rays and anticancer drugs are attenuated because of hypoxia inside the spheroids. However, the impact of the C-ion beam was almost the same as that of the 2D culture, because heavy-particle irradiation was not affected by hypoxia. These results suggest that heavy-particle radiotherapy may be a new therapeutic strategy for overcoming the resistance of cervical adenocarcinoma to treatment.

Perineural Invasion Combined with Pattern C of the Silva Classification System Correlates Poor Prognosis in Cervical Adenocarcinoma Following a Radical Hysterectomy

<h3>Purpose/Objective(s)</h3> The incidence of cervical adenocarcinoma (CA) has been increasing progressively with a younger trend in recent years. However, the conventional risk factors and pathological type of CA were insufficient to predict the prognosis and provide a basis for the treatment. Recently, a few studies have reported that perineural invasion (PNI) and the Silva classification system (SLVCS), a new pathological classification system, have a better impact on treatment strategies and prognosis prediction of CA patients. Their combined application, however, has been rare. Therefore, we retrospectively analyzed the correlation of PNI combined with SLVCS to survival prognosis under standard therapeutic strategies. <h3>Materials/Methods</h3> From January 2010 to November 2021, the comprehensive clinicopathologic data of 118 patients with CA following a radical hysterectomy were retrospectively included. PNI was obtained directly from pathological reports. Meanwhile, the HE staining sections were categorized into pattern A, pattern B and pattern C in accordance with SLVCS. For statistical analysis, statistical software was utilized, with chi square test or Fisher exact probability methods for counting data and Mann-Whitney U test for grading data. The Kaplan–Meier method was used to calculate OS and PFS, and groups were evaluated by log-rank test. <h3>Results</h3> Among 118 patients with CA, there were 17 patients of pattern A (14.4%) and 26 patients of pattern B (22.0%). Remarkably, 75 patients of pattern C (63.6%) accounted for the largest proportion. Meanwhile, 31 (26.3%) of the total patients and 28(37.3%) of pattern C patients showed PNI. Pattern A and B patients were early FIGO stage (IA2-IB3). Pattern C was FIGO stage IB1-IIIC1p. Notably, almost half of PNI patients (13/31, 41.9%) were both FIGO stage IIIC1p and pattern C. Tumor invasion depth, parauterine infiltration, the later FIGO stage and lymphatic vessel invasion were more common in PNI patients (P<0.05). At the end of follow-up, the 5-year PFS and OS of PNI patients (68.41%, 67.74%) were lower than those of no PNI patients (73.96% and 71.32%) (P<0.05). In addition, the 5-year PFS and OS of PNI combined with SLVCS patients were lower than those of the others (P<0.05). <h3>Conclusion</h3> PNI combined with SLVCS may be a reliable system to predict risk in patients with CA. PNI combined with SLVCS patients have a worse prognosis and require a more-aggressive therapeutic approach, especially complicated with tumor invasion depth, parauterine infiltration, the later FIGO stage and lymphatic vessel invasion.

Utility of p16/Ki67 double immunocytochemistry for detection of cervical adenocarcinoma.

Although the incidence of cervical adenocarcinoma has consistently increased, especially among young women, there is no established best means for screening. This study evaluated the screening efficacy of CINtec PLUS (CINtec; p16/Ki67 double immunocytochemistry) expression in cervical glandular cells. Cervical cytology was examined using abnormal glandular cells. The CINtec status of 100 samples with corresponding surgically resected specimens and 11 samples that exhibited negative results for intraepithelial lesion or malignancy at follow-up was analyzed. Additionally, 31 negative samples containing benign glandular cells were included. Of the 142 samples, CINtec status was diffusely positive in 74, focally positive in 24, and negative in 44. The 74 diffusely positive samples included 70 adenocarcinomas (62 cervical, seven uterine, and one ovarian) and four cases of high-grade cervical intraepithelial neoplasia. The 24 focally positive samples included 15 adenocarcinomas (seven cervical, seven uterine, and one fallopian tube) and nine without malignancy. The 44 negative samples included nine adenocarcinomas (five uterine and four cervical) and 35 without malignancy. The sensitivity, specificity, positive predictive value, and negative predictive value of the CINtec diffusely or focally positive cases for cervical adenocarcinomas were 94.5%, 58.0%, 70.4%, and 90.9%, respectively. In CINtec diffusely positive cases, the respective values were 84.9%, 82.6%, 83.8%, and 83.8%, and in women aged ≤39 years the values were 90.6%, 89.5%, 93.5%, and 85.0%, respectively. CINtec may support efficient detection of cervical adenocarcinomas.

Impact of Silva classification system on the survival of HPV-related cervical adenocarcinoma patients with stage I ̃ IIIc1p.

e17505 Background: The incidence of cervical adenocarcinoma is increasing progressively in recent years and shows a younger trend that seriously threatens human health. However, the conventional pathological type of cervical adenocarcinoma is insufficient to predict the prognosis and therapeutic effect. Recently,the Silva classification system, a new pathological classification system was introduced and considered to have a better potential impact on the survival of HPV-related cervical adenocarcinoma patients. Methods: The clinical data of 102 patients with cervical adenocarcinoma from January 2010 to September 2021 were retrospectively included. All patients underwent radical resection of cervical cancer and were diagnosed as cervical adenocarci.noma by pathology.The HE staining sections of the patients were divided into SilvaA, SilvaB, and SilvaC types according to the Silva typing system. SPSS26.0 software was used for statistical analysis, Kaplan-Meier calculation was used for single-factor analysis, and COX stepwise regression model was used for multi-factor analysis. Results: Of the 102 patients with cervical adenocarcinoma who could be graded according to the Silva system, 14 (13.7%, 14/102) were SilvaA, 23 (22.5%, 23/102) SilvaB, and 65 (63.8%, 65/102) SilvaC. SilvaA type cervical adenocarcinoma patients were all stage I (IB1-IB3), no lymphatic or vascular invasion, and all patients were in a survival state by the end of follow-up. All patients with SilvaB cervical adenocarcinoma were stage I (IA2-IB3), without lymphatic or vascular invasion. Among 23 patients with Silva B, 2 patients died due to tumor, and the 5-year PFS and OS were 91.3%. Sixty-five patients with SilvaC type cervical adenocarcinoma (IB1-IIIC1P) and 15 patients died of tumor-related causes. FIGO stage, tumor size, lymph node invasion, and paralegal invasion were the influencing factors for survival and prognosis of SilvaC patients (P &lt;0.05). Conclusions: In the Silva typing system, SilvaC type has the worst prognosis, SilvaA type and SilvaB type are both stages I, without lymph node invasion, and the prognosis is better. Patients with SilvaC type are at the Ib1-IIIC1P stage and may have a lymphatic and vascular invasion. Late FIGO stage, lymph node metastasis, and paralegal infiltration are the influencing factors for survival and prognosis of SilvaC type.

The impact of age, race, and HPV status on the increasing incidence of cervical adenocarcinoma in U.S. women

Objectives: To evaluate the demographic and HPV status in relation to the increasing incidence of adenocarcinoma in the United States. Methods: Data were obtained from the United States Cancer Statistics from 2001 to 2016. SEER*Stat and Joinpoint regression were used to calculate average annual percent change (AAPC). Incidence rates were corrected for hysterectomy using the Behavioral Risk Factor Surveillance System. THe National Health and Nutrition Examination Survey (NHANES) was used to evaluate HPV genotypes in a healthy cohort. Results: Of 201,609 patients with cervical adenocarcinoma between 2001-2016, White, Black, Hispanic, Asian and others comprised 62%, 15.4%, 16.3%, 4.4% and 1.8% of patients. Overall the 40-44 year-old age groups had the highest incidence (2.97 / 100,000). We also found an average annual increase of 2.4% in this age group. (p or =5 partners. Although HPV 16 was the predominant HPV genotype at 18.4%, HPV 18 comprised 9.1% of the HPV positive patients within the study group. Blacks have a two-fold higher rate of HPV 18 infection (3.2% vs 1.3%; p Download : Download high-res image (320KB) Download : Download full-size image Conclusions: The incidence of adenocarcinoma is increasing in the United States. Blacks have a higher incidence of metastatic disease compared to Whites and other races. HPV 18 genotypes were more prevalent in Blacks compared to Whites with no difference HPV 16.

Transcriptome analysis uncovers the diagnostic value of miR-192-5p/HNF1A-AS1/VIL1 panel in cervical adenocarcinoma

Despite the fact that the incidence of cervical squamous cell carcinoma has decreased, there is an increase in the incidence of cervical adenocarcinoma. However, our knowledge on cervical adenocarcinoma is largely unclear. Transcriptome sequencing was conducted to compare 4 cervical adenocarcinoma tissue samples with 4 normal cervical tissue samples. mRNA, lncRNA, and miRNA signatures were identified to discriminate cervical adenocarcinoma from normal cervix. The expression of VIL1, HNF1A-AS1, MIR194-2HG, SSTR5-AS1, miR-192-5p, and miR-194-5p in adenocarcinoma were statistically significantly higher than that in normal control samples. The Receiver Operating Characteristic (ROC) curve analysis indicated that combination of miR-192-5p, HNF1A-AS1, and VIL1 yielded a better performance (AUC = 0.911) than any single molecule -and could serve as potential biomarkers for cervical adenocarcinoma. Of note, the combination model also gave better performance than TCT test for cervical adenocarcinoma diagnosis. However, there was no correlation between miR-192-5p or HNF1A-AS1 and HPV16/18 E6 or E7. VIL1 was weakly correlated with HPV18 E7 expression. In summary, our study has identified miR-192-5p/HNF1A-AS1/VIL1 panel that accurately discriminates adenocarcinoma from normal cervix. Detection of this panel may provide considerable clinical value in the diagnosis of cervical adenocarcinoma.

Expression of Markers of Müllerian Clear Cell Carcinoma in Primary Cervical and Vaginal Gastric-type Adenocarcinomas.

The incidence of cervical adenocarcinoma, both absolute and relative to squamous cell carcinoma, is increasing. Most cervical adenocarcinomas are human papillomavirus associated, although non-human papillomavirus-associated neoplasms exist; the latter include gastric-type adenocarcinoma (GAS) and clear cell carcinoma (CCC). Histologically, these 2 tumors may superficially resemble one other and although morphologic evaluation usually permits a correct diagnosis, immunohistochemistry may be required to resolve diagnostic uncertainty, especially in a small biopsy specimen. Markers of CCC include hepatocyte nuclear factor 1 beta (HNF1β) and Napsin A. In order to explore the utility of these markers in distinguishing between GAS and CCC, we stained 24 cases of GAS (19 cervical, 5 vaginal), 3 of cervical gastric-type adenocarcinoma in situ (gAIS) and 14 CCCs (13 cervical, 1 vaginal) with these antibodies. We found HNF1β expression in 21 of 23 cases of GAS (91.3%; there was no material available for staining in 1 case), 3/3 cases of gAIS (100%) and 10 of 14 (71.4%) CCCs. Napsin A was expressed in 4 of 24 (16.7%) cases of GAS, 0 of 3 (0%) gAIS, and 11 of 14 (78.6%) CCC. On the basis of these findings, Napsin A is of value in resolving diagnostic confusion between GAS and CCC, whereas HNF1β lacks specificity and its use in this setting is discouraged.

Estimating the impact of an organised screening programme on cervical cancer incidence: A 26-year study from northern Italy.

The impact of the organised cervical cancer (CC) screening programmes implemented in Europe since the 1990s has been insufficiently evaluated. We investigated the changes in CC incidence following the introduction of a screening programme in the Emilia-Romagna Region (northern Italy). The study period was 1988-2013. The programme, targeting women aged 25-64 years (1,219,000 in 2018), started in 1998. The annual incidence rates that would be expected in 1998-2013 in the absence of screening were estimated, first, by analysing the annual rates in 1988-1997 with a log-linear model and, second, by analysing the annual rates in 1988-2013 with an age-period model in which the period effect was enforced to be linear. Cervical adenocarcinoma incidence trend over the entire period was used to validate both estimates. Observed annual rates were compared to the two series of expected ones with the incidence rate ratio (IRR). Incidence remained stable during 1988-1997, peaked in 1998 and then decreased until 2007, when it stabilised. The two series of expected rates were virtually coincident and their trends roughly paralleled the stable adenocarcinoma incidence trend. After 2007, the median IRR was 0.60 (95% confidence interval, 0.45-0.81) based on the log-linear model and 0.58 (95% confidence interval, 0.34-0.97) based on the age-period model. Thirty-six to seventy-five CC cases were prevented annually for an average annual frequency of 6.5 per 100,000 women in the target population. In summary, consistent circumstantial evidences were obtained that the organised screening programme brought about a 40% reduction in annual CC incidence after 10 years.

Uterin Serviks Kanserinin Atipik Prezentasyonu: Olgu Sunumu

Increases of uterine cervical adenocarcinoma incidence have been observed in recent years. In this report, we present a rare case of cervical adenocarcinoma, which mimics vesicovaginal fistula. A 40- year-old multigravida patient presented with involuntary leakage of urine that began 6 months ago following dilatation and curettage for her pregnancy with missed abortion. During pelvic examination, exfoliation of perineum as a result of sustained exposure of wetness was observed but the ‘cough stress test’ was negative and nulliparous healthy cervix with clear watery discharge was also observed. Laparotomy with total abdominal hysterectomy and abdominal washing were done. Histological examination revealed diagnosis of cervix adenocarcinoma without lymphovascular and perinueronal invasion and also endometrial adenocarcinoma located on two different focuses without myometrial invasion. An effusive watery vaginal discharge that evaluated mistakenly as urine may be produced by the malignant gynecological adenocarcinoma.

Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions.

The Papanicolaou (Pap) test has indisputably decreased cervical cancer mortality, as rates have declined by up to 80% in the United States since its implementation. However, the Pap test is considered less sensitive for detecting glandular lesions than for detecting those of squamous origin. Some studies have even suggested an increasing incidence of cervical adenocarcinoma, which may be a consequence of a relatively reduced ability to detect glandular lesions with cervical cancer screening techniques. To evaluate the detection rate of glandular lesions with screening techniques currently used for cervical cancer screening and to provide insight as to which techniques are most efficacious in our study population. We retrospectively reviewed any available cytology, human papillomavirus (HPV), and histologic malignancy data in patients diagnosed with adenocarcinoma in situ and adenocarcinoma from 2 geographically and socioeconomically disparate hospital systems. Identified patients having had a negative/unsatisfactory Pap test within 5 years of adenocarcinoma in situ or adenocarcinoma tissue diagnosis were considered Pap test screening failures. Patients with negative HPV tests on cytology samples were considered HPV screening failures. One hundred thirty cases were identified (age range, 22-93 years); 39 (30%) had no Pap history in our files. Eight of 91 remaining cases (8.8%) were screening failures. The detected sensitivity for identifying adenocarcinoma in situ/adenocarcinoma in this study was 91.2% by cytology alone and 92.3% when incorporating HPV testing. The most common cytologic diagnosis was atypical glandular cells (25 cases), and those diagnosed with adenocarcinoma were 7.4 years older than those diagnosed with adenocarcinoma in situ (50.3 versus 42.9 years). Nine of 24 HPV-tested cases (37.5%) were called atypical squamous cell of undetermined significance on cytology. Our results highlight the importance of combined Pap and HPV cotesting. Although the number of cases identified is relatively small, our data suggest screening for squamous lesions facilitates the recognition of glandular lesions in the cervix. Additionally, increased use of combined Pap and HPV cotesting may decrease detection failure rates with regard to glandular lesions.

Response of adenocarcinoma of the uterine cervix to chemoradiotherapy.

The aim of the current retrospective study was to investigate the response of advanced cervical adenocarcinoma (AC) to definitive chemoradiotherapy. Uterine cervical cancer is one of the most common cancer types among females, with squamous cell carcinoma (SQCC) being the most prevalent histological type. The incidence of cervical AC and its variants has markedly increased in recent decades. The current understanding with regard to the treatment of cervical cancer has been established through studies in which the majority of the patients suffered from SQCC, while only a limited number of studies have focused on the treatment of AC. Therefore, the optimal treatment for uterine cervical AC remains unclear. In the present study, data were collected from the medical files of patients who were diagnosed with advanced uterine cervical AC and treated with chemoradiotherapy between 1998 and 2013. Data were also collected from a group of patients with SQCC for comparison with AC patients in terms of response and survival. A total of 68 uterine cervical cancer cases were included, including 29 AC patients and 39 SQCC patients. Compared with the SQCC subgroup, a higher number of AC patients required surgery following chemoradiotherapy due to a lack of response to the initial treatment (5% vs. 31%, respectively; P=0.0065). After a median follow-up period of 10 years, patients with AC exhibited shorter overall survival (7.4 years vs. 11 years for AC and SQCC groups, respectively; P=0.01). Differences in recurrence (40.7% vs. 34.4%; P=0.79) and disease-free interval (1.2 years vs. 2 years; P=0.11) were not statistically significant. The results indicated that cervical AC is less responsive to chemoradiotherapy compared with SQCC.

Abstract 3290: Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma

Abstract Cervical cancer is still a serious problem threatening to women health worldwide. The incidence of cervical adenocarcinoma (AD) is rising in more developed countries. Previously we have identified that glucose-regulated protein 58 (Grp58) serves as a poor independent prognostic factor for cervical AD. The molecular mechanism underlying Grp58 involved cervical AD carcinogenesis is unknown. The DNA microarray and enrichment analysis were used to identify pathway maps perturbed by knockdown of Grp58 expression. The WNT singling map is one of the significant enriched pathways. The β-catenin, vital effector of WNT signaling, was stably accumulated in Grp58 knockdown stable cells. A membrane fashion of β-catenin was observed in Grp58 knockdown but not control cells. By using transwell assay, we have demonstrated that accumulation of β-catenin, which was induced by Grp58 knockdown or lithium chloride treatment, inhibited the migration ability of HeLa cell. Furthermore, an exclusive expression pattern of Grp58 and β-catenin was observed in cervix tissues. In sum, we have demonstrated that β-catenin stability is negatively regulated by Grp58. Overpression of Grp58 might result in lost or decreased of membranous β-catenin in cervical cancer to promote cancer progression. Citation Format: Chia-Jung Liao, Syuan-ling Lin, Tzu-Hao Wang, Kwang-Huei Lin. Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2014-3290

Glucose-regulated protein 58 modulates β-catenin protein stability in a cervical adenocarcinoma cell line

BackgroundCervical cancer continues to threaten women’s health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown.MethodsDNA microarray and enrichment analysis were used to identify the pathways disrupted by knockdown of Grp58 expression.ResultsAmong the pathway identified, the WNT signaling pathway was one of those that were significantly associated with knockdown of Grp58 expression in HeLa cells. Our experiments showed that β-catenin, a critical effector of WNT signaling, was stabilized thereby accumulated in stable Grp58 knockdown cells. Membrane localization of β-catenin was observed in Grp58 knockdown, but not control cells. Using a transwell assay, we found that accumulated β-catenin induced by Grp58 knockdown or lithium chloride treatment inhibited the migration ability of HeLa cells. Furthermore, an inverse expression pattern of Grp58 and β-catenin was observed in cervical tissues.ConclusionsOur results demonstrate that β-catenin stability is negatively regulated by Grp58 in HeLa cells. Overexpression of Grp58 may be responsible for the loss of or decrease in membranous β-catenin expression in cervical AD.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-555) contains supplementary material, which is available to authorized users.

Primary Papillary Serous Carcinoma of Cervix: A Rare Variant of Cervical Malignancy

Papillary serous carcinoma of the uterine cervix is a very rare tumour, and is a recently described variant of cervical adenocarcinoma. It is an aggressive tumour with unpredictable course and poor prognosis. The incidence of cervical adenocarcinoma is 5–15%. This variant accounts for less than 50 cases in literature, has bimodal age distribution with one peak occurring less than 40 years and other occurring greater than 65 years age groups. Here, we present a 53 year-old woman presented with severe low backache and lump abdomen of 4 months duration. Per vaginal examination showed endophytic growth high up in the cervix. Pap smear and cervical biopsy done. Histopathological examination of cervical biopsy revealed papillary serous adenocarcinoma. Later, we received hysterectomy specimen with regional lymph nodes, which showed tumour limited to endocervix.

Prevalence and type distribution of human papillomavirus in cervical adenocarcinoma in Korean women

BackgroundAn increase in incidence of cervical adenocarcinoma (CADC) has been reported in many countries, including Korea. However, few studies describe human papillomavirus (HPV) type distribution among CADC in Asia. Objective and methodsThis was a retrospective, hospital-based observational study between 2005 and 2010 to estimate the overall prevalence and distribution of HPV types among CDAC in Korean women. The study used hematoxylin & eosin and immunohistochemical staining (for the two biomarkers p16 and progesterone receptor [PR]) to diagnose and subtype CADC samples. HPV DNA was amplified by polymerase chain reaction (PCR) and HPV genotypes were identified using reverse hybridization. ResultsOf 196 cases submitted, 89.3% of the cases were confirmed as CADC. The mean age at diagnosis was 47.1 (standard deviation [SD] 11.9) years. No statistically significant differences in mean age at diagnosis by histological subtype were found. HPV DNA was detected in 90.3% (177/196) of CADC. HPV-18 was the most prevalent type (54.2%), followed by HPV-16 (44.1%) and HPV-45 (3.4%). Infection with any high-risk HPV type was identified in 97.7% of HPV-DNA-positive CADC. The biomarker p16 was positive in 92% of CADC cases and PR was positive in 19.6% of CADC. ConclusionHPV DNA was found in the large majority of CADC in Korean women, with HPV-18 being the most common type followed by HPV-16 and HPV-45. This study is among the first in Asia to specifically report HPV type distribution in CADC. This information will help inform policy decisions concerning HPV vaccination for the prevention of CADC.

Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma

The incidence of cervical adenocarcinoma, which accounts for 10-20% of all cervical cancers, has increased continuously in developed countries during the last two decades, unlike squamous cell cervical carcinoma. This increasing trend, noted particularly among women under the age of 40 years, has occurred despite extensive cytological Pap smear screening. A deeper understanding of the etiology of cervical adenocarcinoma, better preventive measures and reliable prognostic markers are urgently needed. The human leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family includes: LRIG1, LRIG2 and LRIG3. LRIG expression has proven to be of prognostic value in different types of human cancers, including breast cancer, early stage invasive squamous cervical cancer, cutaneous squamous cell carcinoma, oligodendroglioma and astrocytoma. LRIG1 functions as a tumor suppressor, while less is known about the functions of LRIG2 and LRIG3. This study evaluated the expression of the three LRIG proteins in tumor specimens from 86 women with pure cervical adenocarcinoma by immunohistochemistry. Possible correlations between LRIG expression and known prognostic factors, including human papillomavirus (HPV) status, FIGO stage and histology were investigated. Patient survival data were collected retrospectively and the possible prognostic value of LRIG protein expression was investigated. High staining intensity of LRIG1 and high fraction of LRIG3-positive cells were significantly associated with patient survival, and positive correlations were found between LRIG1 and LRIG3 staining intensity and HPV status. Thus, the LRIG proteins may be important determinants of cervical adenocarcinoma progression and their diagnostic and prognostic potential should be studied further.

El adenocarcinoma de cérvix como causa infrecuente de sangrado vaginal en la mujer joven

Cervical adenocarcinoma is a less frequent variant than squamous carcinoma. The incidence of cervical adenocarcinoma has been increasing over the last several years. Villoglandular papillary adenocarcinoma usually affects young women and generally has a good prognosis. The treatment of this adenocarcinoma is surgical, with conisation being sufficient in localised cases, but a hysterectomy is often necessary to try and preserve the ovaries and maintain endocrine function.