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Endometrial Cancers (endometrial + cancers)
Selected AbstractsO-13 ENDOMETRIAL CARCINOMA DETECTED WITH SUREPATH LIQUID BASED CERVICAL CYTOLOGY: COMPARISON WITH CONVENTIONAL CERVICAL CYTOLOGYCYTOPATHOLOGY, Issue 2006C. J. Patel Introduction:, Conventional Pap Smear (CPS) has had little impact on the detection of endometrial carcinoma (MC). Although Liquid Based Cytology (LBC) is replacing CPS in the UK, experience with identification of endometrial cancers with this is limited. A few studies of ThinPrep LBC show promise with reported increased detection rate, but to date, there has been no reported study of detection with SurePath LBC. Aim:, The purpose of this 2-year retrospective study was to compare the accuracy of the SurePath LBC with that of conventional smear in detecting endometrial cancers. Methods:, Our study group consisted of all SurePath cases of endometrial atypia/carcinoma diagnosed between 1st Jan 2004 and 31st Dec 2005, following 100% conversion of our laboratory to the SurePath system in 2001. Conventional smears reported over a 6-year period (1993,1998), comprised the control group. Histological follow up was obtained. Results:, Endometrial lesions were reported in 95 (0.07%) of 130352 SurePath LBC smears. These included 70 (0.053%) reports of endometrial atypia, 05 (0.003%) suspicious and 20 (0.015%) diagnostic of endometrial carcinoma. A total of 58 (0.014%) cases of 409495 CPS were diagnosed as endometrial carcinoma. Adequate histological follow up was available in 47 (49.5%) SurePath LBC and 52 (89.6%) conventional cases. In these, the positive predictive value (PPV) for endometrial carcinoma of SurePath LBC was 73.3% compared to 55.4% of CPS. The PPV for endometrial carcinoma of the atypical and suspicious LBC categories was 14.3% and 40% respectively. No categorisation as atypical or suspicious in the conventional study was available for comparison. The sensitivity of the SurePath LBC, calculated from retrograde analysis of histologically diagnosed endometrial cancers during the same period was 40%. Conclusion:, The SurePath LBC is at least an as accurate and sensitive method for detecting endometrial cancer as CPS. [source] ThinPrep Pap tests in patients with endometrial cancer: A histo-cytological correlationDIAGNOSTIC CYTOPATHOLOGY, Issue 7 2007Jianhong Zhou M.D. Abstract The aim of this retrospective study was to correlate cytological diagnoses of endometrial cancers in ThinPrep Pap tests with the histological diagnoses. ThinPrep specimens from 67 patients within 12 mo of the histological diagnosis of endometrial cancer were studied. Of this study sample, 89.6% had abnormal Pap tests. Abnormal Pap tests occurred in 96.8, 68.4, and 100% of patients with grades 1, 2, or 3 endometrial cancers, respectively. Of patients with endocervical involvement, 88.9% had positive or suspicious Pap tests, compared with 41.1% without endocervical involvement (LR = 7.85, P < 0.01). Of patients with ,50% myometrial invasion, 78.9% had positive or suspicious Pap tests, compared with 34.8% with less than 50% invasion (LR = 10.97, P < 0.01). Positive or suspicious Pap tests were found in 59.5 and 32.1% of those with tumors ,3 cm or <3cm, respectively (LR = 4.85, P < 0.05). Diagn. Cytopathol. 2007;35:448,453. © 2007 Wiley-Liss, Inc. [source] Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterationsGENES, CHROMOSOMES AND CANCER, Issue 3 2002Chiara Ghimenti BARD1 (BRCA1-associated RING domain) was identified by yeast two-hybrid screening as a protein interacting with BRCA1. Somatic and germline mutations of BARD1 have been detected in sporadic breast, ovarian, and endometrial cancers. The present study represents the first description of BARD1 germline mutations in hereditary breast and breast/ovarian cancer patients. We analyzed the BARD1 gene in 40 families with hereditary breast and breast/ovarian cancer, tested negative for BRCA1 and BRCA2 mutations. A mutational analysis by PCR-SSCP on the coding region and the exon,intron splice boundaries of the BARD1 gene yielded four different germline mutations. A group of 20 patients diagnosed with sporadic breast cancer below the age of 40 was also examined and only one germline mutation was found. A study of loss of heterozygosity at the BARD1 locus in neoplastic tissues from patients with BARD1 germline mutations was carried out. In all cases, we were unable to find any evidence for allelic deletions. The involvement of BARD1 mutations in the susceptibility to hereditary breast and breast/ovarian cancer is discussed. [source] The association of plasma androgen levels with breast, ovarian and endometrial cancer risk factors among postmenopausal womenINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Kim N. Danforth Abstract Although androgens may play an etiologic role in breast, ovarian and endometrial cancers, little is known about factors that influence circulating androgen levels. We conducted a cross-sectional analysis among 646 postmenopausal women in the Nurses' Health Study to examine associations between adult risk factors for cancer, including the Rosner/Colditz breast cancer risk score, and plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). All analyses were adjusted for age, laboratory batch and other cancer risk factors. Free testosterone levels were 79% higher among women with a body mass index of ,30 vs. <22 kg/m2 (p -trend <0.01) and 25% higher among women with a waist circumference of >89 vs. ,74 cm (p -trend = 0.02). Consuming >30 g of alcohol a day vs. none was associated with a 31% increase in DHEA and 59% increase in DHEAS levels (p -trend = 0.01 and <0.01, respectively). Smokers of ,25 cigarettes per day had 35% higher androstenedione and 44% higher testosterone levels than never smokers (p -value, F -test = 0.03 and 0.01, respectively). No significant associations were observed for height or time since menopause with any androgen. Testosterone and free testosterone levels were ,30% lower among women with a hysterectomy vs. without (both p -values < 0.01). Overall breast cancer risk was not associated with any of the androgens. Thus, several risk factors, including body size, alcohol intake, smoking and hysterectomy, were related to androgen levels among postmenopausal women, while others, including height and time since menopause, were not. Future studies are needed to clarify further which lifestyle factors modulate androgen levels. [source] Activation of epidermal growth factor receptor results in Snail protein but not mRNA overexpression in endometrial cancerJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Susanne Hipp Abstract Reduced E-cadherin expression is associated with tumour progression of many carcinomas, including endometrial cancers. The transcription factor Snail is known as one of the most prominent transcriptional E-cadherin repressors; its regulation in cancer tissues, however, still remains unclear. Here, we report that activation of epidermal growth factor receptor (EGFR) resulted in overexpression of Snail and also identified critical downstream signalling molecules. Stimulation of two endometrial carcinoma cell lines with epidermal growth factor (EGF) lead to an increase of Snail protein expression. In primary human endometrioid endometrial carcinomas Snail protein expression correlated with the activated, phosphorylated form of EGFR (Tyr1086) as revealed by profiling 24 different signalling proteins using protein lysate microarrays. In addition, we observed an inverse correlation between Snail and E-cadherin protein levels in these tumours. Most likely, p38 MAPK, PAK1, AKT, ERK1/2 and GSK-3, are involved in the up-regulation of Snail downstream of EGFR. Snail mRNA expression did not show a correlation with activated EGFR in these tumours. Taken together, profiling of signalling proteins in primary human tissues provided strong evidence that EGFR signalling is involved in Snail protein overexpression. [source] Promoter methylation in circadian genes of endometrial cancers detected by methylation-specific PCRMOLECULAR CARCINOGENESIS, Issue 10 2006Mu-Chin Shih Abstract Methylation of CpG dinucleotides in the promoter sequence of a gene can lead to deregulated and suppressed gene expression. In this study, we have developed procedures for methylation-specific polymerase chain reaction (MSP) and sequencing analysis to determine CpG methylation status of the promoter sequences of nine circadian genes in 35 endometrial cancers (EC) and paired noncancerous endometrial tissues. DNA methylation was found in the promoter sequences of PER1, PER2, and CRY1, but not of other six circadian genes in the ECs and normal tissues examined. Eleven of the 35 EC tissues showed CpG methylation in the promoter sequences of PER1, PER2, or CRY1. Of these 11 cases, 1 had promoter methylation in all the three genes, 1 in PER1 and PER2, 3 in PER1 and CRY1, and 6 in PER1, respectively. In comparison, promoter CpG methylation of PER1, PER2, or CRY1 was found in only 7 of 35 paired noncancerous tissues including 2 in PER1 and PER2, 2 in PER1, and 3 in CRY1. In summary, promoter methylation in the PER1, PER2, or CRY1 circadian genes was detected in about one-third of EC and one-fifth of noncancerous endometrial tissues of 35 paired specimens indicating possible disruption of the circadian clock in the development of EC. © 2006 Wiley-Liss, Inc. [source] Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancerAPMIS, Issue 3 2010JUNG HYE CHOI Choi JH, Song YS, Yoon JS, Song KW, Lee YY. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer. APMIS 2010; 118: 196,202. The enhancer of zeste homolog 2 (EZH2), a member of the polycomb group of proteins, plays an important role in cell proliferation and cell cycle regulation. EZH2 is overexpressed in aggressive forms of prostate, breast, bladder, and endometrial cancers. However, the role of EZH2 expression in gastric cancer has not been fully determined. This study was conducted to investigate the correlation between EZH2 and cell cycle-related molecules, and the clinical value of EZH2 expression in gastric cancer. We analyzed EZH2 expression using Western blotting in AGS, MKN-28, SNU-16, SNU-484, SNU-601, and SNU-638 gastric cancer cell lines. After transfection of EZH2 siRNA into MKN-28 cells, the change in cell cycle-related molecules was assessed by Western blot analysis. Expression of EZH2, Ki-67, and p53 was determined by immunohistochemical staining of tissue microarrays from specimens of 137 cases of resected gastric cancer. We found high expressions of EZH2 in all of the tested gastric cancer cell lines. RNA interference of EZH2 induced upregulation of p53 and HDAC1 and downregulation of cyclin D1 and cyclin E. High EZH2 expression was observed in 60.6% of gastric cancers and in 6.7% of non-neoplastic gastric tissues (p < 0.01); 40.1% were positive for p53 in gastric cancers. High EZH2 expression was correlated with Ki-67 and p53 expressions and was significantly associated with distant metastases and non-signet ring cells. Our results suggest that high EZH2 expression is associated with tumor cell proliferation and metastasis in gastric cancer. [source] Biologic markers in endometrial cancer treatmentAPMIS, Issue 10 2009INGEBORG B ENGELSEN With a lifetime risk among women of 2,3%, endometrial cancer is the most common pelvic gynecologic malignancy in industrialized countries. Approximately 75% of cases are diagnosed at an early stage with a tumor confined to the uterine corpus. Although most patients are cured by surgery alone, about 15,20% with no signs of locally advanced or metastatic disease at primary treatment recurs, with limited responsiveness to systemic therapy. The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with a good prognosis, accounts for the majority of cases and is associated with a low-stage, low-grade and endometrioid histology. In contrast, type II, associated with a poor prognosis, is characterized by a high-stage, high-grade and non-endometrioid histology. However, the prognostic value of this distinction is limited, as up to 20% of type I endometrial cancers recur, while half of type II cancers do not. We review the current literature on epidemiology, etiology, pathology, molecular alterations, staging, treatment and prognostic factors in endometrial cancer. Ongoing molecular-based clinical trials and newly reported molecular alterations with a potential for development of new targeted therapy are discussed. [source] The frequency of significant pathology in women attending a general gynaecological service for postcoital bleedingBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2001Adam N. Rosenthal Objectives To document the frequency of pathology in women who complain of postcoital bleeding. To determine whether negative cervical cytology excludes serious pathology in women with postcoital bleeding. To determine whether postcoital bleeding increases the risk of serious pathology in women with an abnormal smear. Design A retrospective study. Setting A university teaching hospital. Population 314 women with postcoital bleeding seen in the gynaecology service from first January 1988 to 31 December 1994. Methods Women were identified from the computerised records of the colposcopy service and copies of correspondence, which was routinely retained on computer. The latter was searched for the text strings coital and intercourse. Main outcome measure Histopathological diagnosis. Results Twelve women (4%) had invasive cancer: 10 were cervical or vaginal cancers and two endometrial cancers. Eight of the 10 cervical or vaginal cancers were clinically apparent. Four women of these 10 had had a normal smear before being referred for further investigation of postcoital bleeding. Two of these cancers were visible only with the aid of the colposcope. Thus, 0.6% of women attending a gynaecology service with postcoital bleeding, a normal looking cervix and a normal smear had invasive cancer of the cervix. Cervical intraepithelial neoplasia were found in 54 women (17.%) and 15 women (5%) had cervical polyps. Nineteen of the 63 women (30%) with significant pathology had a normal or inflammatory cervical smear. No explanation for the postcoital bleeding was found in 155 women (49 %). Conclusions Although invasive cancer is rare in women with postcoital bleeding, it is much commoner than in the general population. It seems likely that cervical intraepithelial neoplasia is also associated with postcoital bleeding, perhaps because the fragile cervical epithelium becomes detached during intercourse. Postcoital bleeding should continue to be regarded as an indication of high risk for invasive cervical cancer and for cervical intraepithelial neoplasia. Prompt referral to a colposcopy clinic is indicated, but most women with postcoital bleeding will have no serious abnormality. [source] Expression of epithelial membrane protein-2 is associated with endometrial adenocarcinoma of unfavorable outcome,CANCER, Issue 1 2006Madhuri Wadehra PhD Abstract BACKGROUND Epithelial membrane protein 2 (EMP2) is an estrus-regulated tetraspan protein that is required for endometrial competence in blastocyst implantation. EMP2 controls surface levels of several classes of integrin and other cell-interaction molecules, and their trafficking to glycolipid-enriched lipid raft domains is important in receptor signaling. These features suggest that EMP2 may contribute to neoplastic traits of endometrial cancer. The objective of this study was to determine the prevalence of EMP2 expression in endometrial neoplasms and its clinical significance. METHODS EMP2 immunophenotype, histologic diagnosis, grade, the presence of lymphovascular invasion, disease stage, and clinical follow-up were determined for 99 endometrial cancers. RESULTS Significant EMP2 expression (EMP2 positive) was observed in 12 of 99 cancers (9 endometrioid [6 International Federation of Gynecology and Obstetrics Grade 3], 1 serous, 1 mixed endometrioid and serous, and 1 mixed endometrioid and clear cell), and weak EMP2 expression was observed in 11 cancers. EMP2-positive tumors were more likely than others to be myometrium invasive, high stage, and recurrent, persistent, or fatal. The overall median survival for patients with EMP2-positive tumor was only 23 months, whereas the medial survival was not reached for patients with EMP2-weak and EMP2-negative tumors. The median disease-free interval was only 11 months for patients with EMP2-positive tumors and was not reached for patients with EMP2-weak and EMP2-negative tumors. A multivariate analysis of disease-free survival demonstrated independent, negative prognostic significance for EMP2 expression, high stage, and high-risk histologic subtypes. CONCLUSIONS EMP2 expression is a feature of some prognostically unfavorable endometrial cancers. Its utility for clinical decision making and its biologic role in endometrial cancer deserves further study in a larger series of patients. Cancer 2006. © 2006 American Cancer Society. [source] Molecular epidemiological and mutational analysis of DNA mismatch repair (MMR) genes in endometrial cancer patients with HNPCC-associated familial predisposition to cancerCANCER SCIENCE, Issue 9 2008Y. Hirai Recently, a high rate of endometrial cancer has been reported in women with hereditary non-polyposis colorectal cancer (HNPCC), suggesting a relationship between familial endometrial cancers and HNPCC. Familial endometrial cancers constitute only about 0.5% of all endometrial carcinomas and it is essential to examine family histories in detail. A mutational analysis of three DNA mismatch repair (MMR) genes (hMLH1, hMSH2 and hMSH6) in patients with endometrial cancer who meet our criteria for familial predisposition to HNPCC-associated endometrial cancers was performed. Mutations were detected in 18 of the 120 patients (15.0%). Most HNPCC-related endometrial cancers do not meet the New Amsterdam Criteria for HNPCC. These clinical criteria may identify only some HNPCC-associated endometrial cancers. Establishing the correct family history for endometrial cancer patients is important for diagnosing familial endometrial carcinomas. An analysis of MMR genes may be useful for patients with endometrial cancer showing familial aggregation. In addition, gynecologists must be accurately informed, and it is important to perform large-scale, multicenter studies both nationwide and internationally. (Cancer Sci 2008; 99: 1715,1719) [source] Concomitant activation of AKT with extracellular-regulated kinase 1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosissCANCER SCIENCE, Issue 12 2007Noriko Mori Deregulated signaling via the phosphatidylinositol 3-kinase (PI3K) pathway is common in many types of cancer, but its clinicopathological significance in endometrial cancer remains unclear. In the present study, we examined the status of the PI3K signaling pathway, especially in relation to PTEN and PIK3CA status, in endometrioid-type endometrial cancer. The immunohistochemical analysis revealed a high level of phosphorylated (p)-AKT expression, which is a hallmark of activated PI3K signaling, in approximately 60% of endometrial cancers. There was no correlation between p-AKT expression and clinicopathological characteristics, such as International Federation of Gynecology and Obstetrics stage, tumor grade, and myometrial invasion. Unexpectedly, a high level of p-AKT expression occurred independently of the presence of PTEN or PIK3CA mutations. Furthermore, p-AKT expression did not correlate with the expression of potential downstream targets, including p-mTOR and p-FOXO1/3a. In turn, p-AKT expression was strongly associated with extracellular-regulated kinase 1/2 expression (P = 0.0031), which is representative of the activated RAS,MAP kinase pathway. Kaplan,Meier analysis suggested that low p-AKT expression was associated with low rates of relapse-free survival, although the difference was not statistically significant, indicating that AKT activation does not confer worse prognosis. The present study demonstrates the presence of complex signaling pathways that might mask the conventional tumorigenic PTEN,PI3K,AKT,mTOR pathway, and strongly suggests a close association between the extracellular-regulated kinase and PI3K pathways in this tumor type. (Cancer Sci 2007; 98: 1881,1888) [source] | ||||||||||||||||||||||