β-Catenin and FAT1 Protein Expressions for Prediction of Survival Outcome in Type I Endometrial Cancer

2021 ◽  
Vol 104 (5) ◽  
pp. 757-763

ackground: Endometrial cancer (EC) is the second most common female genital tract malignancy and has adverse outcome in the advanced stage. A prognostic marker is needed for marking an accurate prognostic. Objective: To evaluate expression and clinical outcome of CTNNB1 (β-catenin) and FAT atypical cadherin 1 (FAT1), by using immunohistochemical staining in EC type I. Materials and Methods: Seventy-two EC type I cases were selected from Songklanagarind Hospital with clinical data collection. All cases were evaluated by immunohistochemistry using antibodies against β-catenin and FAT1. Results: All cases of EC type I were β-catenin positive and FAT1 negative. Moderate and strong intensity (2+ and 3+) β-catenin cytoplasmic staining showed statistically significant association with low grade EC, and low risk of recurrence disease or metastasis (p<0.05). β-catenin nuclear staining was present in 19 of 28 cases (68%) of EC grade 1 and associated with low grade EC. β-catenin and FAT1 expression were not associated with 5-year overall survival in both univariate and multivariate analyses. Conclusion: β-catenin cytoplasmic staining may be associated with low grade EC, and helpful to predict recurrent risk. However, FAT1 and β-catenin expressions have no statically significant correlation with 5-year overall survival and cannot be used to determine the prognosis in type I EC patients. Keywords: β-catenin, FAT1, Immunohistochemistry, Metastasis, Recurrence, Survival outcome, Type I endometrial cancer

2021 ◽  
Author(s):  
Barbara Gardella ◽  
Mattia Dominoni ◽  
Stefano Bogliolo ◽  
Chiara Cassani ◽  
Giulia Vittoria Carletti ◽  
...  

Abstract Purpose: Type I endometrial cancer is a common disease which takes place in female genital tract. The aim of the work is to asset the feasibility and safety of anastrozole in the palliative treatment of endometrial cancer in elderly women not eligible to standard surgical treatment. Methods: eight patients with histological diagnosis of endometrial cancer were enrolled in this pilot study. Anastrozole was administered 1 mg daily per os after performing an accurate radiological mapping of the lesion. A questionnaire evaluated the quality of life of these patients. Results: the median age was 85 (range 80-88years). The endometrial cancer was confined to the uterus in all patients. No progression of disease was observed. A partial response to the therapy was reported in seven patients, while no response was reported in one patient. A decrease in the symptoms such as pain, vaginal bleeding and vaginal discomfort was reported, as well as no progression of disease. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average rate of follow-up was 18.25 months. Four women died for other reasons, none of them related to endometrial cancer. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported. Conclusion: our preliminary data reported that the palliative use of anastrozole may be a suitable therapy for a good control of early stages of endometrial cancer in inoperable elderly women, having a good compliance and tolerance.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Elisabet Aliagas ◽  
August Vidal ◽  
Laura Texidó ◽  
Jordi Ponce ◽  
Enric Condom ◽  
...  

One of the strategies used by tumors to evade immunosurveillance is the accumulation of extracellular adenosine, which has immunosupressive and tumor promoting effects. The study of the mechanisms leading to adenosine formation at the tumor interstitium are therefore of great interest in oncology. The dominant pathway generating extracellular adenosine in tumors is the dephosphorylation of ATP by ecto-nucleotidases. Two of these enzymes acting sequentially, CD39 and CD73, efficiently hydrolyze extracellular ATP to adenosine. They have been found to play a crucial role in a variety of tumors, but there were no data concerning endometrial cancer, the most frequent of the invasive tumors of the female genital tract. The aim of the present work is to study the expression of CD39 and CD73 in human endometrial cancer. We have analyzed protein and gene expression, as well as enzyme activity, in type I endometrioid adenocarcinomas and type II serous adenocarcinomas and their nonpathological endometrial counterparts. High levels of both enzymes were found in tumor samples, with significantly increased expression of CD39 in type II serous tumors, which also coincided with the higher tumor grade. Our results reinforce the involvement of the adenosinergic system in cancer, emphasizing the relevance of ecto-nucleotidases as emerging therapeutic targets in oncology.


2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.


2020 ◽  
Vol 150 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Lin Li ◽  
Mingming Tang ◽  
Dan Nie ◽  
Jinhai Gou ◽  
Zhengyu Li

2016 ◽  
Vol 126 (6) ◽  
pp. 1788-1794 ◽  
Author(s):  
Yongheng Wang ◽  
Yinyan Wang ◽  
Xing Fan ◽  
Shaowu Li ◽  
Xing Liu ◽  
...  

OBJECTIVEInsular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system's association with survival outcome.METHODSA total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil's classification, was examined using multivariate analyses.RESULTSNinety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil's classification.CONCLUSIONSThe current study's findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 291-291
Author(s):  
Elizabeth Ann Guancial ◽  
Lillian Werner ◽  
Edward Stack ◽  
Rosina Lis ◽  
Sabina Signoretti ◽  
...  

291 Background: DNA repair factors are hypothesized to mediate chemosensitivity to cytotoxic agents that produce DNA damage and may be predictive for response to platinum-based chemotherapeutic regimens. Primary urothelial carcinoma (UC) tumors of patients who developed metastatic disease were evaluated for expression of a panel of DNA repair factors by immunohistochemistry (IHC). Methods: A cohort of 132 clinically annotated, uniformly-treated (platinum-based combination chemotherapy) UC patients who subsequently developed distant metastases with FFPE primary tumor tissue available was identified. Tumor bearing areas were evaluated by a single urologic pathologist. Tissue arrays were constructed for IHC analysis of the following DNA repair factors: ERCC1, Rad 51, BRCA1/2, PAR and PARP1. Tumor was deparaffinized and specific antigen retrieval determined for individual antibodies. Pathologist supervised IHC analysis of nuclear versus cytoplasmic expression was performed using spectral imaging analysis. Overall survival (OS) was defined from start of chemotherapy for metastatic disease to death (N=67) or censored on the last known alive date. Percent of positive nuclear staining was categorized as quartiles or previously identified cut-points. Cox regression evaluated the associations of percent positive nuclear staining levels and OS in multivariable analysis (HRs and 95% CIs included) that controlled for known prognostic variables (performance status and visceral metastases). Results: Higher percentage of nuclear staining of ERCC1 [HR=2.7 (1.5, 4.9), p=0.0007]; Rad51 [HR=5.6 (1.7, 18.3), p=0.005]; and PAR [HR=2.2 (1.1, 4.4), p=0.026] in tumor tissue were associated with poor outcome; each was independent of the other two repair factors and known prognostic variables. Neither nuclear nor cytoplasmic staining for BRCA1/2 or PARP1 reached statistical significance for an association with OS. Conclusions: DNA damage repair factor levels measured by IHC impact outcomes in advanced UC. External validation is ongoing and will be presented. Further studies are required to determine whether these biomarkers are prognostic or predictive in this setting.


2020 ◽  
Author(s):  
Barbara Gardella ◽  
Mattia Dominoni ◽  
Stefano Bogliolo ◽  
Chiara Cassani ◽  
Giulia Vittoria Carletti ◽  
...  

Abstract Purpose: Type I endometrial cancer is a common disease which takes place in female genital tract. The aim of the work is to asset the feasibility and safety of anastrozole in the palliative treatment of endometrial cancer in elderly women not eligible to standard surgical treatment. Methods: eight patients with histological diagnosis of endometrial cancer were enrolled in this pilot study. Anastrozole was administered 1 mg daily per os after performing an accurate radiological mapping of the lesion. A questionnaire evaluated the quality of life of these patients. Results: the median age was 85 (range 80-88years). The endometrial cancer was confined to the uterus in all patients. No progression of disease was observed. A partial response to the therapy was reported in seven patients, while no response was reported in one patient. A decrease in the symptoms such as pain, vaginal bleeding and vaginal discomfort was reported, as well as no progression of disease. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average rate of follow-up was 18.25 months. Four women died for other reasons, none of them related to endometrial cancer. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported. Conclusion: our preliminary data reported that the palliative use of anastrozole may be a suitable therapy for a good control of early stages of endometrial cancer in inoperable elderly women, having a good compliance and tolerance.


Tumor Biology ◽  
2018 ◽  
Vol 40 (6) ◽  
pp. 101042831878480 ◽  
Author(s):  
Pawel Sadlecki ◽  
Jakub Jóźwicki ◽  
Paulina Antosik ◽  
Marek Grabiec

Epithelial ovarian neoplasms are a heterogeneous group including tumor subsets with distinct clinicopathologic and molecular features. Recent evidence from molecular and genomic studies suggests that whereas low-grade serous carcinomas and high-grade serous carcinomas likely develop on two separate pathways, the low-grade serous carcinomas and serous borderline ovarian tumors may represent various stages of the same developmental continuum. The transformation of borderline ovarian tumors into an invasive neoplasm is associated with an array of molecular changes, inter alia controlled by p53 and PI3K/Akt pathway, as well as with a decrease in E-cadherin expression. The latter implies that epithelial–mesenchymal transition is a critical determinant of borderline ovarian tumor invasiveness. The aim of this study was to analyze the expression of transcription factors involved in epithelial–mesenchymal transition: SNAIL, SLUG, TWIST 1, TWIST 2, ZEB 1, and ZEB 2 in borderline tumors and type I ovarian cancers. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses. The expressions for SLUG, TWIST 1, ZEB1, and ZEB 2 were scored based on the nuclear staining, and the expressions of SNAIL and TWIST 2 based on the cytoplasmic and/or nuclear staining. The proportions of ovarian tumors with the immunoexpression of the epithelial–mesenchymal transition transcription factors were 85.7% for SNAIL, 100% for SLUG, 9.5% for TWIST 1, 95.2% for TWIST 2, 23.8% for ZEB 1, and 0% for ZEB 2. The expression patterns of SNAIL, SLUG, TWIST, and ZEB identified in this study suggest that both serous borderline ovarian tumors and type I ovarian cancers undergo dynamic epithelial–mesenchymal interconversions. Our findings obtained in the two groups of tumors which shared some etiopathogenic pathways imply that the expression of the epithelial–mesenchymal transition transcription factors may be activated at early stages of the epithelial–mesenchymal transition, and thus these molecules may play a pivotal role in the development of both serous borderline ovarian tumors and type I ovarian cancer.


2016 ◽  
Vol 128 (4) ◽  
pp. 761-770 ◽  
Author(s):  
Koji Matsuo ◽  
Hiroko Machida ◽  
Donna Shoupe ◽  
Alexander Melamed ◽  
Laila I. Muderspach ◽  
...  

2000 ◽  
pp. 227-242 ◽  
Author(s):  
G Emons ◽  
G Fleckenstein ◽  
B Hinney ◽  
A Huschmand ◽  
W Heyl

Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.


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