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68 results on '"Olkhov‐Mitsel, Ekaterina"'

55. CTNNB1Mutations and Aberrant β-Catenin Expression in Ovarian Endometrioid Carcinoma

Author

Zyla, Roman E., Olkhov-Mitsel, Ekaterina, Amemiya, Yutaka, Bassiouny, Dina, Seth, Arun, Djordjevic, Bojana, Nofech-Mozes, Sharon, and Parra-Herran, Carlos

Abstract

Supplemental Digital Content is available in the text.CTNNB1mutations and aberrant β-catenin expression have adverse prognosis in endometrial endometrioid carcinoma, and recent evidence suggests a prognostic role of β-catenin in ovarian endometrioid carcinoma. Thus, we aimed to determine the prognostic value of the CTNNB1mutational status, and its correlation with β-catenin expression, in a well-annotated cohort of 51 ovarian endometrioid carcinomas. We performed immunohistochemistry for β-catenin and developed an 11-gene next-generation sequencing panel that included whole exome sequencing of CTNNB1and TP53. Results were correlated with clinicopathologic variables including disease-free and disease-specific survival. Tumor recurrence was documented in 14 patients (27%), and cancer-related death in 8 patients (16%). CTNNB1mutations were found in 22 cases (43%), and nuclear β-catenin in 26 cases (51%). CTNNB1mutation highly correlated with nuclear β-catenin (P<0.05). Mutated CTNNB1status was statistically associated with better disease-free survival (P=0.04, log-rank test) and approached significance for better disease-specific survival (P=0.07). It also correlated with earlier International Federation of Gynecology and Obstetrics stage (P<0.05). Nuclear β-catenin, TP53mutations, age, ProMisE group, surface involvement, tumor grade and stage also correlated with disease-free survival. There was no association between membranous β-catenin expression and disease-free or disease-specific survival. CTNNB1mutations and nuclear β-catenin expression are associated with better progression-free survival in patients with OEC. This relationship may be in part due to a trend of CTNNB1-mutated tumors to present at early stage. β-catenin immunohistochemistry may serve as a prognostic biomarker and a surrogate for CTNN1Bmutations in the evaluation of patients with ovarian endometrioid neoplasia, particularly those in reproductive-age or found incidentally without upfront staging surgery.

Published
2021
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57. PD65-01 GERMLINE MUTATIONS IN THE KALLIKREIN 6 REGION AND PREDISPOSITION FOR AGGRESSIVE PROSTATE CANCER

Author

Briollais, Laurent, primary, Ozcelik, Hilmi, additional, Xu, Jingxiong, additional, Kwiatkowski, Maciej, additional, Lalonde, Emilie, additional, Sendorek, Dorota H, additional, Fleshner, Neil E, additional, Recker, Franz, additional, Kuk, Cynthia, additional, Olkhov-Mitsel, Ekaterina, additional, Savas, Sevtap, additional, Hanna, Sally, additional, Juvet, Tristan, additional, Hunter, Geoffrey A, additional, Friedlander, Matt, additional, Li, Hong, additional, Chadwick, Karen, additional, Prassas, Ioannis, additional, Soosaipillai, Antoninus, additional, Randazzo, Marco, additional, Trachtenberg, John, additional, Toi, Ants, additional, Shiah, Yu-Jia, additional, Fraser, Michael, additional, van der Kwast, Theodorus, additional, Bristow, Robert G, additional, Bapat, Bharati, additional, Diamandis, Eleftherios P., additional, Boutros, Paul C, additional, and Zlotta, Alexandre R, additional

Published
2017
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58. Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer

Author

Briollais, Laurent, primary, Ozcelik, Hilmi, additional, Xu, Jingxiong, additional, Kwiatkowski, Maciej, additional, Lalonde, Emilie, additional, Sendorek, Dorota H., additional, Fleshner, Neil E., additional, Recker, Franz, additional, Kuk, Cynthia, additional, Olkhov-Mitsel, Ekaterina, additional, Savas, Sevtap, additional, Hanna, Sally, additional, Juvet, Tristan, additional, Hunter, Geoffrey A., additional, Friedlander, Matt, additional, Li, Hong, additional, Chadwick, Karen, additional, Prassas, Ioannis, additional, Soosaipillai, Antoninus, additional, Randazzo, Marco, additional, Trachtenberg, John, additional, Toi, Ants, additional, Shiah, Yu-Jia, additional, Fraser, Michael, additional, van der Kwast, Theodorus, additional, Bristow, Robert G., additional, Bapat, Bharati, additional, Diamandis, Eleftherios P., additional, Boutros, Paul C., additional, and Zlotta, Alexandre R., additional

Published
2017
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59. p53, Mismatch Repair Protein, and POLEAbnormalities in Ovarian Clear Cell Carcinoma

Author

Parra-Herran, Carlos, Bassiouny, Dina, Lerner-Ellis, Jordan, Olkhov-Mitsel, Ekaterina, Ismiil, Nadia, Hogen, Liat, Vicus, Danielle, and Nofech-Mozes, Sharon

Abstract

Supplemental Digital Content is available in the text.The PROMISE diagnostic algorithm, which uses p53, mismatch repair (MMR) protein immunohistochemistry, and DNA polymerase ε (POLE) exonuclease domain mutation testing, is a reliable surrogate of the molecular group in endometrial carcinoma. Its prognostic value has been validated in endometrial carcinoma and ovarian endometrioid carcinoma. Moreover, a similar prognostic grouping has been recently documented in endometrial clear cell carcinoma. Thus, we aimed to explore the role of these markers in ovarian clear cell carcinoma, another endometriosis-associated malignancy. A total of 90 cases were identified and confirmed after secondary review. Immunohistochemistry for p53, MLH1, MSH2, MSH6, and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. POLEmutational analysis was performed in 47 cases. Results were correlated with clinicopathologic variables including disease-free survival (DFS), overall survival, and disease-specific survival (DSS). Endometriosis was found in 67 (74%) cases. Six (7%) tumors were p53 abnormal, 82 (91%) were p53 normal, and 2 (2%) tumors had MMR deficiency (1 MSH6 loss and 1 MSH2/6 loss; both were p53 normal). Several POLEvariants of unknown significance were detected, but no pathogenic mutations. The mean follow-up period was 43 months (median: 34, range: 1 to 189). Abnormal p53 status was associated with advanced Federation of Gynecology and Obstetrics stage, lymph node metastases, DFS and DSS (P<0.05, Fisher exact test). In univariate analysis, abnormal p53 and positive lymph node status had worse DFS, whereas bilaterality, surface involvement, and advanced stage were associated with worse DFS, overall survival and DSS (P<0.05, Cox regression). On multivariate analysis, only stage retained statistical association with survival. Using a molecular-based approach designed for endometrial carcinoma, most ovarian clear cell carcinomas fall into the copy-number-low molecular subgroup. However, a small but important subset has an abnormal p53 expression (copy-number-high group). This subset is associated with adverse features including extrapelvic disease, nodal metastases, and recurrence similar to endometrial and ovarian endometrioid cancer. Thus, testing for this marker has potential prognostic significance. The role of other markers in the PROMISE algorithm remains to be elucidated, as we found a low frequency of MMR abnormalities and no pathogenic POLEmutations in our series.

Published
2019
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61. Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Author

White-Al Habeeb, Nicole M. A., primary, Ho, Linh T., additional, Olkhov-Mitsel, Ekaterina, additional, Kron, Ken, additional, Pethe, Vaijayanti, additional, Lehman, Melanie, additional, Jovanovic, Lidija, additional, Fleshner, Neil, additional, van der Kwast, Theodorus, additional, Nelson, Colleen C., additional, and Bapat, Bharati, additional

Published
2014
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66. Quantitative DNA methylation analysis of genes coding for kallikrein-related peptidases 6 and 10 as biomarkers for prostate cancer

Author

Olkhov-Mitsel, Ekaterina, primary, van der Kwast, Theodorus, additional, Kron, Ken, additional, Ozcelik, Hilmi, additional, Briollais, Laurent, additional, Massaey, Christine, additional, Recker, Franz, additional, Kwiatkowski, Maciej, additional, Fleshner, Neil, additional, Diamandis, Eleftherios, additional, Zlotta, Alexandre, additional, and Bapat, Bharati, additional

Published
2012
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67. Can immune markers help identify fast relapse in patients with muscle invasive bladder cancer?

Author

Olkhov-Mitsel E, Hodgson A, Liu SK, Vesprini D, Bayani J, Bartlett JMS, Xu B, and Downes MR

Subjects
Adult, Aged, Aged, 80 and over, Carcinoma, Transitional Cell metabolism, Female, Humans, Immunohistochemistry, Male, Middle Aged, Muscles metabolism, Muscles pathology, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Prognosis, Tumor Microenvironment immunology, Urinary Bladder Neoplasms metabolism, Antigens, CD metabolism, Biomarkers, Tumor metabolism, Carcinoma, Transitional Cell pathology, Neoplasm Invasiveness pathology, Neoplasm Recurrence, Local diagnosis, Urinary Bladder Neoplasms pathology
Abstract

The aim of this pilot study was to assess the role of immune markers in fast relapse (<2 years) of high-grade muscle invasive urothelial carcinomas of the bladder (HGUC) treated by cystectomy. A series of 40 such cases was investigated for immune protein (CD3, CD4, CD8, CD20, CD68, CD163, FOXP3 and PD-1) status by immunohistochemistry. Decreased expression of all immune cell markers was observed in tumors of patients who relapsed quickly. In Kaplan-Meier (log-rank test) analysis, low CD3, CD4 and CD8 expression was associated with fast relapse (P = 0.005, 0.028, 0.036 respectively). Additional evaluation of the immune transcriptome by NanoString Human PanCancer Immune Panel v.1.1 has identified 5 differentially expressed genes significantly associated with fast relapse. Among these, KLRB1 and HLA-DQA1 were also significant on Kaplan-Meier analysis (log-rank test P = 0.007 and 0.006, respectively). These findings strengthen the potential clinical utility and, hence, the need for further evaluation of immune markers in HGUC prognostication., (Copyright © 2020. Published by Elsevier GmbH.)

Published
2020
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68. Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer.

Author

Briollais L, Ozcelik H, Xu J, Kwiatkowski M, Lalonde E, Sendorek DH, Fleshner NE, Recker F, Kuk C, Olkhov-Mitsel E, Savas S, Hanna S, Juvet T, Hunter GA, Friedlander M, Li H, Chadwick K, Prassas I, Soosaipillai A, Randazzo M, Trachtenberg J, Toi A, Shiah YJ, Fraser M, van der Kwast T, Bristow RG, Bapat B, Diamandis EP, Boutros PC, and Zlotta AR

Subjects
Aged, Chromosome Mapping, Disease-Free Survival, Germ-Line Mutation, Haplotypes, Humans, Male, Middle Aged, Neoplasm Grading, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Kallikreins genetics, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology
Abstract

Background: There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa)., Methods: We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort, whereas PLCO data were provided through database of Genotypes and Phenotypes ( dbGaP ). The influence of SNPs of interest on biochemical-free survival was evaluated in a cohort of localized PCa from the International Cancer Genome Consortium (ICGC; n = 130) analyzed with next-generation sequencing. Single- and multi-SNP association studies, as well as haplotype analyses, were performed. All statistical tests were two-sided., Results: Several SNPs in very strong linkage disequilibrium in the KLK 6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (odds ratio [OR] = 3.51-3.64, 95% confidence interval [CI] = 2.01 to 6.36, P = 1.0x10 -5 -8.4x10 -6 ) and validation (OR = 1.89-1.96, 95% CI = 0.99 to 3.71, P = .04-.05) cohorts. The overall test of haplotype association was highly statistically significant in each cohort ( P = 3.5x10 -4 and .006, respectively) and in the three data sets combined ( P = 2.3x10 -5 ). These germline SNPs independently predicted relapse in the ICGC cohort (hazard ratio = 3.15, 95% CI = 1.57 to 6.34, P = .001)., Conclusions: Our fine-mapping study has identified novel loci in the KLK 6 region strongly associated with aggressive PCa., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Published
2017
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