Risk Of Endometrial Carcinoma Research Articles

The role of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) in endometrial carcinoma

Objective: Insulin resistance is a high risk factor of Endometrial Carcinoma (EC). Insulin like Growth Factor Binding Protein-Related Protein 1 (IGFBP-rP1) could lead to insulin resistance due to its high affinity with insulin. The role of IGFBP-rP1 in EC is still unclear. Method: The IGFBP-rP1 was overexpressed at the cellular level first, and then its effect on the growth of endometrial carcinoma cells was observed and its regulatory mechanism was investigated. Results: Our study showed that IGFBP-rP1 upregulation decreased the proliferation of cells and the proportion of S+G2/M phase, but increased the apoptosis of human endometrial cancer cells HEC-1A. The expression of p-ERK1/2 was inhibited, while the concentration of rhIGFBP-rP1 increased. Nevertheless, IGFBP-rP1 was highly expressed in EC tissues. Further examination revealed that the DNA hypomethylation in the promoter region of IGFBP-rP1 was correlated with the high mRNA and protein expression levels of IGFBP-rP1 in EC tissues. Conclusion: These results indicate that the DNA hypomethylation of IGFBP-rP1 can be used to predict high risk of EC. Further study may be required to confirm the predictor role of the methylation of IGFBP-rP1 in EC.

Combined external beam radiotherapy and vaginal brachytherapy versus vaginal brachytherapy in stage I, intermediate- and high-risk cases of endometrium carcinoma.

PurposeRandomized trials on the effect of external beam radiotherapy (EBRT) with or without vaginal brachytherapy (VBT) for endometrial carcinoma are very few. In view of this, the current study was conducted with the hypothesizes: whether the escalated dose of 26 Gy (VBT alone) in comparison with various major international trials (PORTEC-2) has any difference in rates of disease-free and overall survival with fewer adverse effects in low resource setting like India.Material and methodsAn open-labeled, non-inferiority, randomized control trial was undertaken at a regional cancer center among patients with stage IA or IB high-intermediate risk endometrial carcinoma. A total of 50 patients were divided equally among two arms of combined EBRT with VBT (arm I) and VBT alone (arm II). A dose of 50-50.4 Gy in 25-28 fractions of EBRT with 2 fractions of VBT 6.5 Gy each were delivered to patients in arm I and 4 fractions of VBT 6.5 Gy each to patients in arm II, and were followed up for 60 months.ResultsDuring the median follow-up of 36.5 months, two patients developed loco-regional recurrence in arm II, three (arm II), and one (arm I) developed distant metastasis. The 5-year survival rates for arms I and II were 96.0% vs. 92.0% overall, and 88.0% vs. 84.0% disease-free, respectively, and were not found to be statistically significantly different. Dermatological, gastro-intestinal toxicities, and cystitis were lower in the VBT group compared to combined group.ConclusionsVBT alone is as effective as EBRT+VBT in ensuring loco-regional control and achieving comparable survival rates, with fewer toxic effects for patients with stage I intermediate- and high-risk endometrial carcinoma. The dose escalation did not make a difference in the survival rates and was like in the other major trials (PORTEC-2).

Cost-effectiveness of adjuvant intravaginal brachytherapy in high-intermediate risk endometrial carcinoma

PURPOSEWe assessed the cost-effectiveness of adjuvant intravaginal brachytherapy (IVBT) vs. observation after total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO) for high-intermediate risk (HIR) endometrial carcinoma. Methods AND MATERIALSA Markov model was used to assess the cost-effectiveness of IVBT by comparing average cumulative costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) between patients allocated to (1) ‘observation’ or (2) ‘IVBT’ after TH/BSO. We used a prototype Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)–defined HIR patient in the base case analysis. We calibrated the model to match the outcomes reported in the PORTEC-1 and PORTEC-2 trials. Utilities were obtained from published estimates, and costs were calculated based on Medicare reimbursement ($5445 for IVBT). The societal willingness-to-pay threshold was set at $100,000 per QALY. The time horizon was 5 years. ResultsIVBT was associated with a net increase of 0.094 QALYs (4.512 vs. 4.418) as well as an increase in mean cost ($17,453 vs. $15,620) relative to observation. The ICER for IVBT was $19,500 per QALY. On one-way sensitivity analysis, IVBT remained cost-effective when its cost was less than $12,937. If the probability of vaginal recurrence in the observation arm was increased or decreased by 25%, the ICER became $1335 per QALY and $87,925 per QALY, respectively. Probabilistic sensitivity analysis revealed that IVBT was the preferred management option in 86% of simulations. ConclusionsIVBT is cost-effective compared with observation after TH/BSO for HIR endometrial carcinoma by commonly accepted willingness-to-pay thresholds.

Estrogen and insulin synergistically promote type 1 endometrial cancer progression

ABSTRACTDespite evidence that estrogens and insulin are related to type 1 endometrial carcinoma (EC), their synergistic role has not been analyzed. Here, we investigated how estrogens cooperate with insulin to promote type 1 EC progression. We examined the clinical significance of serum estrogen and insulin levels using type 1 EC patients and control subjects. Univariate and multivariate logistic regression analyses for total, premenopausal, and postmenopausal subjects were performed. Type 1 EC risk was evaluated with respect to estrone, estradiol, and insulin levels based on odds ratios (ORs) using stratified data. Cell growth in vitro and in vivo, effects of insulin and estradiol on apoptosis and cell cycle distribution were measured after estradiol and insulin stimulation. Estrone and insulin concentrations were significantly high in type 1 EC patients and retained positive associations with type 1 EC after adjustment for BMI, WHR, diabetes, and hypertension. The odds ratio was significantly high for type 1 EC patients with higher levels of estrone/estradiol and insulin than for patients with higher levels of either estrone/estradiol or insulin, suggesting that estrogen and insulin play a synergistic role in type 1 EC carcinogenesis and progression. Compared to EC cells and cell-based xenografts treated with estradiol or insulin alone, those treated with estradiol and insulin exhibited stronger stimulation. Estrogen and insulin play synergistic roles in type 1 EC carcinogenesis and progression, extending our understanding of EC risks.

EP29.06: Metabolic syndrome and risk of endometrial carcinoma among asymptomatic, postmenopausal, urban Sri Lankan females: a community cohort follow‐up study

Oral Presentation Abstract (OP 023), 130th Anniversary International Medical Congress, Sri Lanka Medical Association, 13th-16th July 2017 Colombo, Sri Lanka

Risk of Serous Endometrial Carcinoma in Women With Pathogenic BRCA1/2 Variant After Risk-Reducing Salpingo-Oophorectomy.

It has recently been shown that the risk of a rare subtype of endometrial carcinoma (serous type) in women carrying a germline BRCA1/2 pathogenic variant is increased. We assessed the incidence of serous endometrial carcinoma in an independent prospective cohort study of 369 BRCA1/2 women (1779 woman-years of follow-up) who underwent risk-reducing salpingo-oophorectomy by laparoscopy. This occurrence in two BRCA1 carriers led us to estimate that BRCA1/2 carriers present a higher risk than the control population (standardized incidence ratio = 32.2, 95% confidence interval = 11.5 to 116.4, P < .001, two-sided chi-square test, 1 degree of freedom). In addition, in both tumors, the wild-type BRCA1 allele was lost, indicating the inactivation of the BRCA1 gene and arguing for a link with endometrial carcinogenesis. Prophylactic hysterectomy could be discussed with informed women through a shared decision-making process although the estimated 3% life-long risk is moderate. Additional studies are required to establish future prophylactic surgery guidelines.

Significance of matrix metalloproteinase-1 and -3 gene polymorphisms and their expression in normal and neoplastic endometrium

BackgroundMatrix metalloproteinases (MMPs) play a fundamental role in tissue degradation or remodeling and involved in all stages of tumor progression. However, the role of the MMPs polymorphisms with endometrial carcinoma has not been fully examined in Egyptian patients. Therefore, we planned this study to evaluate associations of the MMP-1 (−1607 1G/2G) and MMP-3 (−1171 5A/6A) polymorphisms and their immune reactive protein combinations with endometrial carcinoma susceptibility and prognosis in Egyptian patients. MethodsParaffin-embedded tissue samples from 40 women with endometrial carcinoma and 30 controls were immunohistochemically stained for MMP-1and MMP-3 expression. Tissue MMPs levels were analyzed by ELISA technique, and tissue samples were genotyped for MMP-1 and MMp-3 gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Resultswe recorded a significant increase of MMP-1 levels in endometrial carcinoma patients more than controls, to be more increased with advanced stages and grades of the carcinoma. Whereas, the MMP-3 tissue levels showed non-significant changes among patients and controls and even among different stages and grades of cancer.Patients with endometrial carcinoma exhibited a higher distribution of MMP-11G/2G or 2G/2G genotypes compared with controls. Tumors containing the 2G allele expressed MMP-1 protein more frequently than those of 1G/1G genotype. The overall genotype and alleles distribution of the MMP-3 polymorphism in patients was not different from that of controls. The haplotype 2G-6A was associated with a significantly increased risk of endometrial carcinoma as compared with the 1G-5A haplotype. ConclusionThe MMP-1 (−1G/2G) SNP and MMP 2G/6A haplotype may modify susceptibility and are associated with a higher risk of endometrial carcinoma. Otherwise, the MMP-3 (5A/6A) promoter SNP is unlikely to be associated with endometrial carcinoma in the Egyptian population.

Tamoxifen gynecological side effects

Prospective comparative study done in basrah maternity and child hospital over a period of two years from 2002- 2004 , on breast cancer patients treated with tamoxifen which is estrogen receptors modulators with paradoxical effects ( agonist on some tissue and antagonist on others. This study aimed To compare side effect of tamoxifen on both studied groups Premenopausal and postmenopausal.This study included96 Symptomatic pre and postmenopausal breast cancer treated patients with tamoxifen assassed by history and then examination was performedThen endometrium assessed by transabdominal ultrasound to check thickness then almost all patients subjected to endometrial biopsy under general anesthesia, about 45.8% of patients between 50-60 years of age 41.6% of patients had advanced stages of cancer , vaginal bleeding which is the most common symptom symptoms presented in 68.7% ,while 22.8% , 8.28% had vaginal discharge and pain respectively.ultrasound findings showed 22.9% endometrial thickness less than 6mm , 41.6% endometrial thickness 1 cm and more ,10.3% showed polyps and fibroid . no statistical difference between pre and postmenopausal inUSS findings with p value = 7.81, x2= 13.7, df=321.2% showed atrophic endometrium, 16.9% showed endometrial hyperplasia , bulk 44.6% showed non secretory ( proliferative) , with no cases of endometrial carcinoma . No, statistical difference between pre and postmenopausal findingsP value = 9.49 , x2 8.652 , df= 4 .In conclusion the main sharing symptoms in both groups was vaginal bleeding, USS had a poor predictive value in detecting changes in both studied groupOur study did not confirm risk of endometrial carcinoma , with no statistical difference in risk of hyperplasia between pre and postmenopausal studied groups.

National trends, outcomes, and costs of radiation therapy in the management of low- and high-intermediate risk endometrial carcinoma.

9 Background: Our objective was to assess treatment patterns, outcomes, and costs for women with low- (LIR) and high-intermediate risk endometrial cancer (HIR) who are treated with and without adjuvant radiotherapy (RT). Methods: All pts with endometrioid endometrial cancer who underwent surgery from 2000 – 2011 were identified from the SEER – Medicare database. LIR was defined as G1-2 tumors with &lt;50% myometrial invasion or G3 with no invasion. HIR was defined as G1-2 tumors with ≥50% or G3 with &lt;50% invasion. Pts were categorized according to whether they received adjuvant RT (vaginal brachytherapy [VBT], external beam radiotherapy [EBRT], or both) or no RT. All costs incurred up to 6 months postoperatively were analyzed. Outcomes were compared using the χ2test and a Cox PH regression model. Multivariate analyses were performed on both survival and costs. Results: 10,842 pts were included, of which 70% were LIR and 30% were HIR. 9% of pts with LIR had RT, compared to 46% of those with HIR. Among all pts who underwent RT, the use of VBT increased from 25% in 2000 to 71% in 2011, while EBRT use declined from 41% to 18%, and concurrent VBT/EBRT declined from 34% to 11% (p&lt;0.001). In the LIR group, there was no difference in 10-year overall survival (OS) between pts who had RT and those who did not (67% vs. 65%, multivariate HR 0.95, 95% CI 0.81 – 1.11). In the HIR group, pts who underwent RT had a significant increase in 10-year OS (60% vs. 47%, multivariate HR 0.75, 95% CI 0.67 – 0.85). Similar outcomes were noted on subgroup analysis stratifying by RT modality. RT was associated with an increased risk of gastrointestinal (7% vs. 4%, p&lt;0.001), genitourinary (2% vs. 1%, p&lt;0.001), and hematologic (16% vs. 12%, p&lt;0.001) 2-year complications. Compared to pts who only had surgery, RT was associated with increased mean adjusted costs ($22.5k vs. $14.4k, p&lt;0.001). Costs for pts receiving VBT, EBRT, and concurrent VBT/EBRT were $20.6k, $23.3k, and $26.5, respectively (p&lt;0.001). Conclusions: RT was associated with improved OS in women with HIR, but not in the LIR cohort. RT also had significantly increased costs and a higher morbidity risk. In the absence of other risk factors, consideration of observation without RT in LIR may be reasonable.

Histopathological findings in women that living Elazig with abnormal uterine bleeding: in 20 years

Aim: Abnormal uterine bleeding refers to any uterine bleeding that occurs in excessive amounts of regular menstrual bleeding or any postmenopausal bleeding. The present study aims to determine histopathological findings in Turkish women with abnormal uterine bleeding in ElazA½A°. Material and Methods: Retrospectively 420 women with abnormal uterine bleeding were included in the study. Hematoxylin and eosin sections of the cases were re-evaluated by a single pathologist. Results: Of the 316 premenouposal cases %37,02 was diagnosed as (n=117) proliferative endometrium, %22,46 as (n=71) secretuar endometrium, as %3,79 (n=12) desidualisation, as %1,26 (n=4) atrophy, as %2,53 (n=8) placental tissue, as %12 (n=38) dysfunctional uterine bleeding, %12,34 (n=39) as endometrial polyp, %7,9 (n=25) as endometrial hyperplasia, and %0,63 (n=2) as endometrial adenocarcinoma. Of the 104 postmenouposal cases diagnosed as %10,57 (n=11) proliferative endometrium, %0,96 as (n=1) secretuar endometrium, %17,30 (n=18) as desidualisation, %13,46 (n=14) as endometrial polyp, %39,42 (n=41) atrophy, %12,5 (n=13) as endometrial hyperplasia, %5,76 (n=6) as endometrial adenocarcinoma. Conclusions: In our region, because endometrial sampling results belong patients with abnormal uterine bleeding which is usually concordant to age and menstrual cycle, We conclude that non-invasive methods should be tried before sampling. Endometrial carcinoma risk is consistent with the literature,so endometrial samplings should not be avoided.

Morphometric and DNA Image Analysis of Endometrial Hyperplasia and Carcinoma.

Endometrial hyperplasia is believed to increase the risk of endometrial carcinoma and represents a spectrum of morphologic and biological alterations of endometrial glands and stroma ranging from an exaggerated physiological state to carcinoma in situ. Considering the overlap between the various entities, it is not surprising that the morphologic assessment of endometrial lesions is particularly challenging. This work aimed to evaluate endometrial lesions according to their nuclear and glandular morphometric parameters, their D score, and their DNA ploidy, which help in making an accurate diagnosis. In this study, 50 endometrial biopsy specimens were stained with hematoxylin and eosin for their histopathologic and morphometric study and Feulgen stain for DNA analysis. The cases were classified into 20 cases of simple hyperplasia, 10 cases of atypical hyperplasia, and 20 cases of endometrial carcinoma. Morphometric analysis of nuclear, glandular, and stromal parameters was performed using the Leica Qwin 500 image analysis system. In the studied cases, a significant difference was found in the mean values of the morphometrical parameters of endometrial lesions, including the nuclear area and the nuclear roundness, and all glandular measurements including their complexity, area, volume percentage of stroma, and D score were significantly different. The DNA index and diploid and aneuploid values could differentiate significantly between endometrial lesions. We conclude that nuclear morphometric evaluation of the hyperplastic and carcinomatous endometrium may be used as an ancillary technique in the diagnosis of atypical changes occurring in precancerous endometrial lesions. In addition, DNA and D score assessment may be a reproducible and accurate predictor of the outcome of endometrial hyperplasia and may add some objective criteria for the correct diagnosis of difficult cases.

Highlights of This Issue

The association between aspirin use and risk of pancreatic cancer has been inconsistent across studies. Risch and colleagues performed a population-based study of pancreatic cancer patients and control subjects in Shanghai, China. Participants were asked about episodes of regular use of aspirin, tablets per day or week, and ages that use started and stopped. Ever-regular use of aspirin was associated with lowered risk of pancreatic cancer. Risk decreased 8% per each cumulative year of use. Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half.The effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. Menthol-glucuronide (MG) has been identified as the most significant metabolite directly related to smoking. Hsu and colleagues studied MG in relation to smoking behavior and metabolomic profiles. Smokers smoked two cigarettes in the laboratory one hour apart, and blood nicotine, MG, and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Plasma MG boost is a new smoking behavior biomarker that may provide novel information over self-reported use of menthol cigarettes.While most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis, the relatively low fraction of endometrial carcinoma patients with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of these high-risk patients is necessary to tailor treatment. Nucleotyping refers to the characterization of cell nuclei by image cytometry and assessment of chromatin structure by nuclear texture analysis. This method has not been evaluated in preoperative curettage specimens from endometrial carcinoma patients. The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated by Hveem and colleagues in specimens from endometrial carcinoma patients. Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for endometrial carcinoma risk stratification.Early-life socioeconomic status (SES) may play a role in cancer risk in adulthood; however, measuring SES retrospectively presents challenges. Stroup and colleagues used parental occupation on birth certificates to ascertain early-life SES. Cancer incidence was then determined by linkage to the Utah Cancer Registry. Females with low SES at birth had lower risk of breast cancer compared with those in the highest SES group. SES was inversely associated with melanoma and prostate cancer. Women born into lower SES neighborhoods had a significantly increased risk for invasive cervical cancer, and neighborhood SES had similar effects for melanoma and prostate cancers. Individual SES derived from parental occupation at birth was associated with altered risk for several cancer sites.

Epidemiology of Endometrial Carcinoma: Etiologic Importance of Hormonal and Metabolic Influences.

Endometrial carcinoma is the most common gynecologic cancer in developed nations, and the annual incidence is projected to increase, secondary to the high prevalence of obesity, a strong endometrial carcinoma risk factor. Although endometrial carcinomas are etiologically, biologically, and clinically diverse, hormonal and metabolic mechanisms are particularly strongly implicated in the pathogenesis of endometrioid carcinoma, the numerically predominant subtype. The centrality of hormonal and metabolic disturbances in the pathogenesis of endometrial carcinoma, combined with its slow development from well-characterized precursors in most cases, offers a substantial opportunity to reduce endometrial carcinoma mortality through early detection, lifestyle modification, and chemoprevention. In this chapter, we review the epidemiology of endometrial carcinoma, emphasizing theories that link risk factors for these tumors to hormonal and metabolic mechanisms. Future translational research opportunities related to prevention are discussed.

ERCC1 and XRCC1 but not XPA single nucleotide polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

Our study aimed to investigate the correlation between single nucleotide polymorphisms of ERCC1/XRCC1/XPA genes and postoperative chemotherapy efficacy and prognosis of endometrial carcinoma. Our study included 108 patients with endometrial carcinoma and 100 healthy participants. ERCC1 rs11615/XRCC1 rs25487/XPA rs1800975 gene polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism. Then the chemotherapy efficacy and toxic effects of the patients were assessed. The genotype and allele frequency of ERCC1 rs11615/XRCC1 rs25487 in the case group were significantly different from that in the control group (all P<0.05). The patients with AA + GA in ERCC1 rs11615 had an increased risk of endometrial carcinoma than those with GG, and the risk of endometrial carcinoma for patients with AA + GA was also higher in comparison with patients with GG genotype in XRCC1 rs25487 (all P<0.05). GG on both ERCC1 rs11615/XRCC1 rs25487 had a higher effective rate of chemotherapy than GA + AA (all P<0.05). ERCC1 rs11615/XRCC1 rs25487 gene polymorphisms were linked with toxic effects in liver, kidney, and nervous system. ERCC1 rs11615/XRCC1 rs25487, muscular invasion, and tumor stage were independent risk factors for the prognosis of endometrial carcinoma (all P<0.05). However, no significant associations were observed between XPA rs1800975 polymorphism and chemotherapy efficacy and prognosis of endometrial carcinoma (all P>0.05). These results indicated that ERCC1 and XRCC1 but not XPA polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

Uterine Carcinosarcoma: Clinicopathological Features and Prognostic Factors

Uterine carcinosarcoma is a rare and aggressive biphasic malignancy and is currently included in the high risk endometrial carcinoma group. The aims of this study were to determine the clinicopathological profile, treatment, recurrence/progression patterns, survival and prognostic factors. Retrospective study of 42 patients, surgically staged and followed-up at a cancer centre, between 2005 and 2013. Clinical data was retrieved from records and pathological characteristics were reviewed for this study. Median age was 72 years (61 - 78) and the majority presented comorbid diseases. Stage distribution as follows: 13 (31.0%) stage I; eight (19.0%) stage II; nine (21.4%) stage III; and 12 (28.6%) stage IV. Chemotherapy was instituted in 12 patients and 21 received radiotherapy. Disease progressed in 16 patients and recurred in nine after a short interval. Median overall survival was 18 months (6.8 - 40) and median disease-free survival was 6 months (0 - 22.8). The only independent prognostic factor related with poor survival was serosal invasion (p = 0.02; HR adjusted 4.22; IC 95% 1.29 - 13.79). In accordance to other studies, diagnosis of uterine carcinosarcoma is frequently done with advanced disease and presents a high rate of progression/recurrence. The variable which has been consistently identified as main prognostic factor is stage, but in this study the only independent factor was serosal invasion. The present study represents the larger series of uterine carcinosarcoma studied in Portugal and reflects the clinical presentation, histopathological characteristics and stage at diagnosis and confirms the aggressiveness of this rare tumor.

Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution.

The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined. Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013. Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years. To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2017;125:205-211. © 2016 American Cancer Society.

The rs6983267 SNP and long non-coding RNA CARLo-5 are associated with endometrial carcinoma.

The single nucleotide polymorphism (SNP) rs6983267 and cancer-associated region long non-coding RNA (CARLo-5) are associated with various human cancers. This study aimed to investigate the expression of CARLo-5 in endometrial carcinoma (EC) and its relationship with clinicopathological features and patient survival. The association of the rs6983267 SNP with EC risk and its involvement in the regulation of CARLo-5 expression in EC were investigated. The rs6983267 SNP was genotyped by polymerase chain reaction (PCR) and ligase detection reaction in 543 EC patients and 584 controls. The expression of CARLo-5 in 108 EC tissues and 66 normal endometrial tissues (NETs) was determined using quantitative real-time PCR. The genotype and allele distributions of the rs6983267 SNP differed significantly between patients and controls. There was a significant correlation between the rs6983267 genotypes and lymph node metastasis of EC patients (P = 0.026). CARLo-5 expression was significantly higher in EC tissues than in NETs (P < 0.001) and significantly associated with FIGO stage (P = 0.029) and lymph node metastasis (P = 0.030). Patients with high CARLo-5 expression had significantly shorter overall survival than those with low CARLo-5 expression (P = 0.003). The rs6983267 genotype was significantly correlated with CARLo-5 expression (P < 0.05). In conclusion, CARLo-5 was identified as a pro-oncogenic lncRNA that may play an important role in EC progression and represent a prognostic marker for EC. The expression of CARLo-5 was significantly correlated with the rs6983267 genotype associated with increased susceptibility to EC. Environ. Mol. Mutagen. 57:508-515, 2016. © 2016 Wiley Periodicals, Inc.

Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations

The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.

Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions.

Background:Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions.Methods:A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB.Results:The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%.Conclusions:CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.

Predictors of progestin therapy response in endometrial hyperplasia: An immunohistochemical study

Background: Women with endometrial hyperplasia have an elevated risk of endometrial carcinoma .The first line of treatment of endometrial hyperplasia in premenopausal women is progestin treatment with variable response. Objectives: To evaluate the predictive value of immunohistochemical (IHC) biomarkers in progestin treatment for cases having endometrial hyperplasia.Methods: A prospective trial was conducted among 50 premenopausal women with menometrorrhagia. Histopathological evaluation confirmed endometrial hyperplasia in pre-treatment endometrial biopsy [without atypia (n=43) and atypia (n=7)]. All patients treated with oral progestin for 3-6 months. Endometrial immunohistochemical examination for progesterone receptors, Bel-2 and p53 were analyzed in basal blocks.Results: Study participants were classified into two groups, Group One showed endometrial response (n = 38) and Group Two showed non-response or histological progression (n=12). Immunohistochemical expression was expressed as a histopathological immunoreactive score (IRS). Immunoreactive score for progesterone receptors were significant higher in responders. Absence of progesterone receptors and presence of p53 predicted non-responder status.Conclusions: Progesterone receptor expression may be a predictive biomarker of progestin response and p53 expression may be a predictive biomarker of progestin resistance.