scholarly journals OP015/#492 Further stratification of no specific molecular profile (NSMP/P53WT) endometrial carcinomas to refine prognosis and identify therapeutic opportunities

2021 ◽  
Author(s):  
E Thompson ◽  
J Huvila ◽  
D Chiu ◽  
S Leung ◽  
A Lum ◽  
...  
Keyword(s):  
Molecular Profile ◽  
Endometrial Carcinomas

scholarly journals Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3124
Author(s):  
Mikko Loukovaara ◽  
Annukka Pasanen ◽  
Ralf Bützow
Keyword(s):  
Risk Factors ◽  
Mismatch Repair ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
New Therapeutic Approaches ◽  
Increased Risk ◽  
Mmr Deficiency ◽  
Endometrial Carcinomas ◽  
Risk Of Cancer

The aggressiveness of mismatch repair (MMR) deficient endometrial carcinomas was examined in a single institution retrospective study. Outcomes were similar for MMR proficient (n = 508) and deficient (n = 287) carcinomas, identified by immunohistochemistry. In accordance with molecular classification based on The Cancer Genome Atlas (TCGA), tumors with abnormal p53 staining or polymerase-ϵ exonuclease domain mutation were excluded from the MMR proficient subgroup, termed as “no specific molecular profile” (NSMP). Compared with NSMP (n = 218), MMR deficiency (n = 191) was associated with poor disease-specific survival (p = 0.001). MMR deficiency was associated with an increased risk of cancer-related death when controlling for confounders (hazard ratio 2.0). In the absence of established clinicopathologic risk factors, MMR deficiency was invariably associated with an increased risk of cancer-related death in univariable analyses (hazard ratios ≥ 2.0). In contrast, outcomes for MMR deficient and NSMP subgroups did not differ when risk factors were present. Lymphatic dissemination was more common (p = 0.008) and the proportion of pelvic relapses was higher (p = 0.029) in the MMR deficient subgroup. Our findings emphasize the need for improved triage to adjuvant therapy and new therapeutic approaches in MMR deficient endometrial carcinomas.

Correlation of PD-L1 expression with immunohistochemically determined molecular profile in endometrial carcinomas

2020 ◽  
Vol 477 (6) ◽  
pp. 845-856 ◽  
Author(s):  
Gozde Kir ◽  
Tuce Soylemez ◽  
Zeynep Cagla Olgun ◽  
Abdullah Aydin ◽  
W. Glenn McCluggage
Keyword(s):  
Molecular Profile ◽  
Endometrial Carcinomas

scholarly journals A Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas

2021 ◽  
Vol 145 (11) ◽  
pp. 1367-1378
Author(s):  
Minhua Wang ◽  
Pei Hui
Keyword(s):  
Copy Number ◽  
Treatment Strategies ◽  
The United States ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
Cancer Genome Atlas ◽  
Endometrial Carcinomas ◽  
Genome Atlas

Context.— Endometrial carcinoma is the most common gynecologic malignancy in the United States and has been traditionally classified based on histology. However, the distinction of certain histologic subtypes based on morphology is not uncommonly problematic, and as such, immunohistochemical study is often needed. Advances in comprehensive tumor sequencing have provided novel molecular profiles of endometrial carcinomas. Four distinct molecular subtypes with different prognostic values have been proposed by The Cancer Genome Atlas program: polymerase epsilon ultramutated, microsatellite instability hypermutated, copy number low (microsatellite stable or no specific molecular profile), and copy number high (serouslike, p53 mutant). Objective.— To discuss the utilities of commonly used immunohistochemical markers for the classification of endometrial carcinomas and to review the recent advancements of The Cancer Genome Atlas molecular reclassification and their potential impact on treatment strategies. Data Sources.— Literature review and authors' personal practice experience. Conclusions.— The current practice of classifying endometrial cancers is predominantly based on morphology. The use of ancillary testing, including immunohistochemistry, is helpful in the identification, differential diagnosis, and classification of these cancers. New developments such as molecular subtyping have provided insightful prognostic values for endometrial carcinomas. The proposed The Cancer Genome Atlas classification is poised to gain further prominence in guiding the prognostic evaluation for tailored treatment strategies in the near future.

Clinical and molecular profile of patients with gonadal dysgenesis attending tertiary care hospital.

2014 ◽  
Author(s):  
Vasundhera Chauhan ◽  
Madan Lal Khurana ◽  
Poonam Gupta ◽  
Iram Sabir ◽  
A.C Ammini
Keyword(s):  
Gonadal Dysgenesis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Molecular Profile ◽  
Care Hospital

Молекулярная биология менингиом головного мозга

2017 ◽  
pp. 82-91
Author(s):  
В.А. Бывальцев ◽  
И.А. Степанов ◽  
Е.Г. Белых ◽  
А.И. Яруллина
Keyword(s):  
Gene Therapy ◽  
Proton Therapy ◽  
Genetic Factors ◽  
Intracranial Tumor ◽  
Molecular Profile ◽  
Genetic Changes ◽  
Treatment Techniques ◽  
Downstream Effects ◽  
Si Rna ◽  
The Relationship

Цель обзора - анализ современных данных литературы о нарушении внутриклеточных сигнальных путей, играющих ведущую роль в развитии менингиом, генетических и молекулярных профилях данной группы опухолей. К настоящему времени изучено множество аберрантных сигнальных внутриклеточных путей, которые играют важнейшую роль в развитии менингиом головного мозга. Четкое понимание поврежденных внутриклеточных каскадов поможет изучить влияние генетических мутаций и их эффектов на менингиомогенез. Подробное исследование генетического и молекулярного профиля менингиом позволит сделать первый уверенный шаг в разработке более эффективных методов лечения данной группы интракраниальных опухолей. Хромосомы 1, 10, 14, 22 и связанные с ними генные мутации ответственны за рост и прогрессию менингиом. Предполагается, что только через понимание данных генетических повреждений будут реализованы новейшие эффективные методы лечения. Будущая терапия будет включать в себя комбинации таргетных молекулярных агентов, в том числе генную терапию, малые интерферирующие РНК, протонную терапию и другие методы воздействия, как результат дальнейшего изучения генетических и биологических изменений, характерных для менингеальных опухолей. Meningiomas are by far the most common tumors arising from the meninges. A myriad of aberrant signaling pathways involved with meningioma tumorigenesis, have been discovered. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. An understanding of the genetic and molecular profile of meningioma would provide a valuable first step towards developing more effective treatments for this intracranial tumor. Chromosomes 1, 10, 14, 22, their associated genes, have been linked to meningioma proliferation and progression. It is presumed that through an understanding of these genetic factors, more educated meningioma treatment techniques can be implemented. Future therapies will include combinations of targeted molecular agents including gene therapy, si-RNA mediation, proton therapy, and other approaches as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

2020 ◽  
Vol 66 (1) ◽  
pp. 71-78
Author(s):  
Lev Bershteyn ◽  
Aleksandr Ivantsov ◽  
Aglaya Ievleva ◽  
A. Venina ◽  
I. Berlev
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Tumor Tissue ◽  
Immunohistochemical Analysis ◽  
The Body ◽  
Molecular Profile ◽  
Total N ◽  
Number Of Patients ◽  
Her 2

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

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