scholarly journals Low Expression of Stanniocalcin 1 (STC-1) Protein Is Associated With Poor Clinicopathologic Features of Endometrial Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Masuma Khatun ◽  
Elina Urpilainen ◽  
Anne Ahtikoski ◽  
Riikka K. Arffman ◽  
Annukka Pasanen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Stress Responses ◽  
Myometrial Invasion ◽  
Clinicopathologic Features ◽  
Obese Women ◽  
Glycoprotein Hormone ◽  
Large Tumor ◽  
Tissue Samples ◽  
Dna Mismatch ◽  
Endometrial Epithelium

Stanniocalcin-1 (STC-1) is a glycoprotein hormone involved in diverse biological processes, including regulation of calcium phosphate homeostasis, cell proliferation, apoptosis, inflammation, oxidative stress responses, and cancer development. The role of STC-1 in endometrial cancer (EC) is yet to be elucidated. In this study, we investigated the protein expression pattern of STC-1 in a tissue microarray (TMA) cohort of hysterectomy specimens from 832 patients with EC. We then evaluated the prognostic value of STC-1 expression regarding the clinicopathologic features and patients survival over a period of 140 months. Our results revealed that in EC tissue samples, STC-1 is mainly localized in the endometrial epithelium, although some expression was also observed in the stroma. Decreased STC-1 expression was associated with factors relating to a worse prognosis, such as grade 3 endometrioid tumors (p = 0.030), deep myometrial invasion (p = 0.003), lymphovascular space invasion (p = 0.050), and large tumor size (p = 0.001). Moreover, STC-1 expression was decreased in tumors obtained from obese women (p = 0.014) and in women with diabetes mellitus type 2 (DMT2; p = 0.001). Interestingly, the data also showed an association between DNA mismatch repair (MMR) deficiency and weak STC-1 expression, specifically in the endometrial epithelium (p = 0.048). No association was observed between STC-1 expression and disease-specific survival. As STC-1 expression was particularly low in cases with obesity and DMT2 in the TMA cohort, we also evaluated the correlation between metformin use and STC-1 expression in an additional EC cohort that only included women with DMT2 (n = 111). The analysis showed no difference in STC-1 expression in either the epithelium or the stroma in women undergoing metformin therapy compared to metformin non-users. Overall, our data may suggest a favorable role for STC-1 in EC behavior; however, further studies are required to elucidate the detailed mechanism and possible applications to cancer treatment.

scholarly journals Endometrial cancer and microsatellite instability status

Open Medicine ◽  
2014 ◽  
Vol 10 (1) ◽  
Author(s):  
Daiva Kanopiene ◽  
Jolanta Vidugiriene ◽  
Konstantinas Povilas Valuckas ◽  
Giedre Smailyte ◽  
Saule Uleckiene ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Myometrial Invasion ◽  
Repair System ◽  
High Status ◽  
Clinicopathologic Characteristics ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Clinicopathologic Parameters ◽  
Analysis System

AbstractMicrosatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. Material and methods: MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. Results and conclusions: One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups – MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

scholarly journals DNA Mismatch Repair Protein Immunohistochemistry and MLH1 Promotor Methylation Testing for Practical Molecular Classification and the Prediction of Prognosis in Endometrial Cancer

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 279 ◽  
Author(s):  
Jisup Kim ◽  
Jin Kong ◽  
Wookyeom Yang ◽  
Hanbyoul Cho ◽  
Doo Chay ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Promoter Methylation ◽  
Molecular Classification ◽  
Clinicopathologic Features ◽  
Immune Markers ◽  
Dna Mismatch ◽  
Sporadic Cancer ◽  
Mmr Deficiency

The incidence of endometrial cancer is rapidly increasing worldwide, and its molecular classification has gained importance for new therapeutic approaches. This study sought to examine the clinicopathologic features and immune markers associated with the DNA mismatch repair (MMR) status and MLH1 promoter methylation status of endometrial cancer patients. A total of 173 patients with primary endometrial cancer who had received a hysterectomy were evaluated for four MMR proteins (MLH1, MSH2, MSH6, and PMS2), immune markers (CD8, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1)) and p53 by immunohistochemistry (IHC), followed by an MLH1 methylation test. Patients were classified into MMR deficiency or proficiency, sporadic cancer, or probable Lynch syndrome (PLS), and the clinicopathologic features (including the expression of peritumoral immune markers) and prognosis of each group were compared. Patients with MMR deficiency or PLS showed an increase in immune markers compared those with MMR proficiency or sporadic cancer, respectively, and PLS demonstrated higher immune marker expression than MLH1 promoter methylation. Regarding prognosis, patients with MMR deficiency showed significant adverse overall survival (OS) when in stages I and II. Practical molecular classifications based on p53 staining results, in addition to MMR or PLS status, revealed an increased predictive ability for OS compared with the European Society of Medical Oncologists (ESMO) risk groups. The results of this study suggest that PLS may be a better candidate for an immune checkpoint inhibitor than MMR deficiency. The practical molecular classification contributes not only to the screening of Lynch syndrome, but also assists in predicting the prognosis in endometrial cancer.

scholarly journals Characteristics of endometrial carcinoma in obese women

2010 ◽  
Vol 63 (9-10) ◽  
pp. 709-714 ◽  
Author(s):  
Predrag Vukomanovic ◽  
Ranko Kutlesic ◽  
Milan Stefanovic ◽  
Mileva Milosavljevic ◽  
Jasmina Popovic ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Myometrial Invasion ◽  
Figo Stage ◽  
Stage I ◽  
Nuclear Grade ◽  
Obese Group ◽  
Type I ◽  
Cancer Type ◽  
Obese Women ◽  
Grade Ii

Introduction. In most developed countries, endometrial cancer appears as most frequent invasive neoplasm of genital tract. Obesity is one of most important risk factors. Aim of study was to establish characteristics endometrial cancer in obese women. Material and methods. The study included 50 surgically treated women with endometrial cancer. According body mass index they were divided into two groups - group A (30 obese women), group B (20 non-obese women). Results and Discussion. Non-obese women with endometrial cancer are statistically significantly older than obese. Menopausal status, parity are not statistically significant. The obese group most frequently includes endometrioid type of tumor, while non-obese group most frequently includes non-endometrioid types of endometrial cancer. Over 50% thick myometrial invasion is statistically more frequent in non-obese group than in obese group. In obese group, less than 50% thick myometrial invasion, is statistically significant in comparison to non-obese group. High-differentiated endometrial cancer(G1) is statistically significantly more present in obese women than non-obese. Low-diferentiated endometrial cancer is statistically more frequent in non-obese women than in obese. Most frequent in both groups is NG2. According to FIGO stage I, disease is statistically significantly more frequent in obese group than in non-obese. In non-obese group, total number of deseased in higher stages (II and III) is statistically significantly higher than in stage I. Conclusion. Endometrial cancer present in obese women is mostly endometroid type I, with slow myometrial invasion, with hystological grade I, nuclear grade II in FIGO stage I of disease. In non-obese women, non-endometrioid cancer - type II is more frequent, with faster myometrial invasion, hystological grade II and III, nuclear grade II, in FIGO stage II of disease.

Mismatch repair protein loss and microsatellite instability in cholangiocarcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 237-237 ◽  
Author(s):  
Lipika Goyal ◽  
Vikram Deshpande ◽  
Daniel C Chung ◽  
Ryan Thomas Groeschl ◽  
T. Clark Gamblin ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Massachusetts General Hospital ◽  
Positive Lymph Node ◽  
Clinicopathologic Features ◽  
Protein Loss ◽  
Tissue Samples ◽  
Dna Mismatch ◽  
Initial Cohort ◽  
History Of

237 Background: Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch Syndrome, is an autosomal dominant syndrome characterized by mutations in genes involved in DNA mismatch repair (MMR) and consequent microsatellite instability (MSI). These genetic aberrations lead to an increased incidence of multiple malignancies including colorectal and endometrial cancer, among others. While an association between biliary tumors and HNPCC has been proposed, no published studies have documented MMR protein loss and MSI in a series of biliary tumor samples. After diagnosing cholangiocarcinoma (CCA) in two clinic patients known to have HNPCC and incidentally noting MMR protein loss and MSI in their tumor, we conducted an exploratory study to evaluate the frequency of MMR protein loss and MSI in patients with CCA. Methods: Discarded tissue samples from patients with CCA treated at the Massachusetts General Hospital (n=44) were evaluated for the loss of MLH1, PMS2, MSH2, and MSH6 with immunohistochemical staining. The results were correlated with clinicopathologic features, and the MSI status was collected from the medical record. Results: Four (9.1%) of 44 patients were found to have loss of at least two MMR proteins: 2 pts had MSH2/MSH6 loss, 1 had MLH1/PMS2 loss, and 1 had loss of all 4 proteins. Two patients had previously been tested for microsatellite instability and both were MSI-high. The clinicopathologic features of the 4 patients included: median age 54.5 yo; M:F 1:3; diagnosed with ≥ 1 HNPCC-related malignancy 1/4; family history of ≥ 2 HNPCC-related tumors 2/4, intrahepatic:extrahepatic CCA 3:1; moderately-poorly:poorly differentiated 2:2; T1:T2 3:1; ≥1 positive lymph node 1/4; lymphovascular invasion 2/3; perineural invasion 2/4. Conclusions: MMR protein loss was discovered in 9.1% of patients with CCA in this initial cohort. A second validation cohort from a different institution is currently being tested, and the results will be presented at the meeting. CCA may be an underappreciated co-morbid neoplasm in the spectrum of tumors for HNPCC. MMR protein loss should be further explored as a mechanism of oncogenesis in CCA, and clinicians should be aware of this malignancy in surveillance of patients with HNPCC.

A Clinical and Biological Comparison Between Malignant Mixed Müllerian Tumors and Grade 3 Endometrioid Endometrial Carcinomas

2009 ◽  
Vol 19 (2) ◽  
pp. 261-265 ◽  
Author(s):  
Amy E. Bland ◽  
Rebecca Stone ◽  
Cara Heuser ◽  
Jianfen Shu ◽  
Amir Jazaeri ◽  
...  
Keyword(s):  
Uterine Cancer ◽  
Growth Factor Receptor ◽  
Myometrial Invasion ◽  
Clinicopathologic Features ◽  
Tissue Samples ◽  
Free Interval ◽  
Egfr Expression ◽  
Phosphorylated Akt ◽  
Her 2 ◽  
Grade 3

Objective:To examine the clinicopathologic features, progression-free interval, and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC) and malignant mixed müllerian tumors (MMMTs). Akt, epidermal growth factor receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also investigated. Associations between phosphorylated Akt and clinicopathologic features were tested.Methods:One hundred nineteen women whose conditions were diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met inclusion criteria. Retrospective data review was performed. In addition, Akt and EGFR protein expression was measured in tissue samples using Western blotting and immunohistochemistry. Fluorescence in situ hybridization was used to assay HER-2/neu gene amplification.Results:Fifty-nine patients with MMMT and 60 patients with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more likely to be African American (P = 0.049), have a family history of breast cancer (P = 0.039), have disease involving the uterine cervix (P = 0.007), and experience postoperative complications (P = 0.012). Patients with MMMT had a significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and survival (55 vs 92 months, P = 0.001) than patients with G3 EEC.Grade 3 EEC and MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46, P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The mesenchymal component of MMMT preferentially demonstrated EGFR expression relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu amplification was observed in 1 of 37 samples.Conclusions:Improved therapy is warranted for both poorly differentiated EEC and MMMT. Recognition of similarities and differences between MMMT and other high-grade histologic types of uterine cancer may provide rationale for new treatment approaches possibly incorporating targeted biological therapies.

CD44 expression in papillary serous endometrial carcinoma

2003 ◽  
Vol 13 (4) ◽  
pp. 480-484 ◽  
Author(s):  
S. Hosford ◽  
J. Elliott ◽  
Z.-W. Ma ◽  
R. Majeste ◽  
B. Dubeshter
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Myometrial Invasion ◽  
Cervical Cytology ◽  
Tumor Type ◽  
Nodal Metastases ◽  
Malignant Cells ◽  
Clinicopathologic Features ◽  
Tumor Spread ◽  
Cd44 Expression

The objective of this paper is to evaluate the relationship between CD44 expression and the clinicopathologic features of papillary serous endometrial cancer. CD44 expression was assessed in 32 cases of papillary serous endometrial carcinoma by standard immunohistochemical staining techniques. Clinicopathologic features including myometrial invasion, nodal metastases, tumor spread, stage, and the shedding of malignant cells on cervical cytology were reviewed. The Chi-square test was used for statistical analysis.CD44 was not expressed in 81% of patients with papillary serous endometrial carcinoma. Malignant cells were seen on cervical cytology in 68% of all cases with significantly more in the CD44-negative group (78% vs. 33%, P 0.05). CD44 expression was not related to stage, myometrial invasion, nodal involvement, or intraperitoneal spread. We conclude that the cell adhesion molecule CD44 is expressed infrequently in papillary serous endometrial carcinoma. Shedding of malignant cells on cervical cytology is common in papillary serous endometrial cancer and occurs more frequently in CD44-negative cases. CD44 expression doesn't appear to be related to known prognostic features such as nodal metastases or stage. The biologic aggressiveness of this tumor type may, in part, be related to its lack of CD44 expression.

scholarly journals Comparison of MRI findings with actual HPE findings in case of carcinoma endometrium

2016 ◽  
Author(s):  
Shaveta Gupta
Keyword(s):  
Endometrial Cancer ◽  
Lymph Node ◽  
Myometrial Invasion ◽  
Lymph Node Involvement ◽  
Common Finding ◽  
Mri Findings ◽  
Pelvic Mri ◽  
Histopathological Findings ◽  
Node Involvement ◽  
Cervical Involvement

Objectives: The objectives of this study is to investigate the correlation of magnetic resonance imaging (MRI) in predicting the depth of myometrial invasion, cervical involvement and lymph node involvement and actual histopathological findings in the women with endometrial cancer. Methods: This is a reterospective study of the patients of endometrial cancer from Nov 2011 to Jan 2016 who underwent Surgery (Total abdominal Hystrectomy with B/l salpingoophorectomy with peritoneal washings with b/l pelvic lymphadenectomy with or without para aortic lymphadenectomy) at our centre Max Superspeciality Hospital. CE MRI Pelvis has been done pre operatively in every patient. After the surgery Histopathological reports of the specimen checked and compared with MRI findings of that case. The purpose of the study is to evaluate the validity of MRI findings of endometrial cancer in comparison to final histopathological findings. Results: For the detection of myometrial invasion, overall sensitivity of MRI is 93.9%, specificity is 66.6%, for cervical involvement Senstivity is 60% and specificity 1s 93.75% and for detection of lymph node involvement sensitivity is 66.6% and specificity is 93.5%. Most common Finding on MRI is thickened endometrium with disruption of Junction jone. Conclusions: Preoperative pelvic MRI is a sensitive method of identifying invasion to the myometrium in endometrial cancer. MRI Is a sensitive noninvasive modality in predicting locoregional spread in ca endometrium. Senstivity in detecting Myometrial invasion is high but sensitivity is less in detecting cervical involvement and lymph node involvement is less.

PET Parameters are Useful in Predicting Endometrial Cancer Risk Classes and Prognosis

2020 ◽  
Author(s):  
Adnan Budak ◽  
Emrah Beyan ◽  
Abdurrahman Hamdi Inan ◽  
Ahkam Göksel Kanmaz ◽  
Onur Suleyman Aldemir ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Myometrial Invasion ◽  
Risk Groups ◽  
Total Sample ◽  
Tumor Stage ◽  
Low Risk ◽  
Tumor Diameter ◽  
Grade 3 ◽  
Fdg Pet Ct

Abstract Aim We investigate the role of preoperative PET parameters to determine risk classes and prognosis of endometrial cancer (EC). Methods We enrolled 81 patients with EC who underwent preoperative F-18 FDG PET/CT. PET parameters (SUVmax, SUVmean, MTV, TLG), grade, histology and size of the primary tumor, stage of the disease, the degree of myometrial invasion (MI), and the presence of lymphovascular invasion (LVI), cervical invasion (CI), distant metastasis (DM) and lymph node metastasis (LNM) were recorded. The relationship between PET parameters, clinicopathological risk factors and overall survival (OS) was evaluated. Results The present study included 81 patients with EC (mean age 60). Of the total sample, 21 patients were considered low risk (endometrioid histology, stage 1A, grade 1 or 2, tumor diameter < 4 cm, and LVI negative) and 60 were deemed high risk. All of the PET parameters were higher in the presence of a high-risk state, greater tumor size, deep MI, LVI and stage 1B-4B. MTV and TLG values were higher in the patients with non-endometrioid histology, CI, grade 3 and LNM. The optimum cut-off levels for differentiating between the high and low risk patients were: 11.1 for SUVmax (AUC = 0.757), 6 for SUVmean (AUC = 0.750), 6.6 for MTV(AUC = 0.838) and 56.2 for TLG(AUC = 0.835). MTV and TLG values were found as independent prognostic factors for OS, whereas SUVmax and SUVmean values were not predictive. Conclusions The PET parameters are useful in noninvasively differentiating between risk groups of EC. Furthermore, volumetric PET parameters can be predictive for OS of EC.

scholarly journals TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features

2021 ◽  
Vol 147 (4) ◽  
pp. 1125-1135
Author(s):  
Sang Kyum Kim ◽  
Jang-Hee Kim ◽  
Jae Ho Han ◽  
Nam Hoon Cho ◽  
Se Joong Kim ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Malignant Neoplasm ◽  
Clinicopathologic Features ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Tert Promoter Mutations ◽  
Formalin Fixed Paraffin Embedded ◽  
Penile Squamous Cell Carcinoma ◽  
Promoter Mutations

Abstract Purpose Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. Methods In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. Results Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. Conclusion Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

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