scholarly journals Prognostic Role of FGFR3 Expression Status and Tumor-Related MicroRNAs Level in Association with PD-L1 Expression in Primary Luminal Non-Muscular Invasive Bladder Carcinoma

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 305
Author(s):  
Ekaterina Blinova ◽  
Anton Buzdin ◽  
Dmitry Enikeev ◽  
Dmitry Roshchin ◽  
Maria Suntsova ◽  
...  

Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: high grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03–2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92–1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17–0.42] p = 0.003) were associated with relapse-free survival. Conclusions: tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression.

2020 ◽  
Author(s):  
Daniele Baiz ◽  
Caterina Negroni ◽  
Sara Ferluga ◽  
Emanuela Ercolano ◽  
Claire L Adams ◽  
...  

Abstract Background: Meningiomas are the most common primary CNS tumors. According to the World Health Organization Classification (WHO), they are classified as benign (grade I), atypical (grade II), and anaplastic/malignant (grade III). Chemotherapy has proven ineffective in treating these tumors, which are primarily managed by surgery, radiotherapy, or a combination of them. Morbidity and mortality correlate with meningioma grade. Currently, risk assessment for treatment is based on the radiological assessment of tumor size, tumor growth rate, and/or clinical progression of symptoms. Methods: We performed a cancer miRNA array in an in vitro model of meningioma in order to identify circulating biomarkers in meningioma patients. We validated the miRNA biomarker candidate in cells and tissues and analyzed its regulation. We then investigated expression in tissues and blood. Results: We identified miR-9-1 as significantly overexpressed in atypical and anaplastic cells compared to benign. We further demonstrated that miR-9-1 overexpression is due to increased levels of FOS via upregulation of the EGFR receptor, and showed that miR-9-1 and FOS are upregulated in a cohort of higher-grade meningioma biopsies. Next, we isolated circulating exosomes from meningioma patients’ serum samples, and found higher levels of miR-9-1 in higher-grade compared to low-grade meningiomas patients. Conclusions: Overall, our study shows overexpression and the mechanism of miR-9-1 regulation and suggests miR-9-1 as a novel circulating biomarker candidate to identify tumor grade in meningioma.


2015 ◽  
Vol 112 (47) ◽  
pp. E6525-E6534 ◽  
Author(s):  
Yunan Yang ◽  
Reinier Hernandez ◽  
Jun Rao ◽  
Li Yin ◽  
Yazhuo Qu ◽  
...  

Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. 64Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ2 = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.


2000 ◽  
Vol 124 (2) ◽  
pp. 216-220 ◽  
Author(s):  
Katherine Allan ◽  
Richard C. K. Jordan ◽  
Lee-Cyn Ang ◽  
Michael Taylor ◽  
Beverley Young

Abstract Background.—Cyclins are proteins that are expressed during the progression of a normal cell through the cell cycle. In a number of cancers, overexpression of cyclin A and cyclin B1 proteins has been reported, and in some instances the levels of expression correlated well with the grades of malignancy. The expression of cyclin A and cyclin B1 proteins in astrocytoma may be linked to the histologic grade or proliferative activities. Objective.—To study the expression of cyclin A and cyclin B1 proteins in astrocytomas and correlate the labeling indices (LIs) of cyclin A and cyclin B1 with histologic grade and Ki-67 LI. Design.—The surgical biopsy specimens from 65 adults with astrocytomas were reviewed and divided into grades based on the World Health Organization system. The paraffin sections were immunostained using primary antibodies against Ki-67, cyclin A, and cyclin B1. The LIs of these astrocytomas for the 3 different antibodies were determined by computerized image analysis. Results.—The cyclin A LI showed good correlation with astrocytoma grade and Ki-67 LI. Both the nuclear and cytoplasmic cyclin B LIs correlated well with the tumor grade but showed poor correlation with Ki-67 LI. Conclusions.—This study suggests that although both cyclin A and B protein expression are related to the grade of malignancy in astrocytomas, cyclin A levels more generally reflect the proliferative state of these tumors. We also provide indirect evidence that cyclin B1 is associated with the aberrant progression through the G2-M phase checkpoint in astrocytomas.


2009 ◽  
Vol 133 (2) ◽  
pp. 303-308 ◽  
Author(s):  
Zahida Parveen ◽  
Karen Thompson

Abstract Subcutaneous panniculitis-like T-cell lymphoma is a primary T-cell lymphoma that preferentially involves the subcutaneous tissue. Although subcutaneous panniculitis-like T-cell lymphoma has been recognized as a distinctive entity in the category of peripheral T-cell lymphoma in the World Health Organization classification, its diagnostic criteria has been redefined by the recent World Health Organization–European Organization for Research and Treatment of Cancer classification for primary cutaneous lymphomas. Subcutaneous panniculitis-like T-cell lymphoma is now restricted to primary cutaneous T-cell lymphoma expressing αβ T-cell receptor phenotype. These lymphomas are usually CD3+, CD4−, CD8+, and CD56−, and usually have an indolent clinical course. The clinicopathologic features, differential diagnosis, immunophenotypic characteristics, and molecular features of subcutaneous panniculitis-like T-cell lymphoma are presented in light of the recent World Health Organization–European Organization for Research and Treatment of Cancer classification.


2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.


2019 ◽  
Vol 90 (28) ◽  
Author(s):  
Prisciane Cardoso Silva ◽  
Marina Soares Mota ◽  
Stella Minasi Oliveira

Objetivo: Buscar na literatura instrumentos utilizados para avaliar a qualidade de vida de pessoas com estomias intestinais. Metodologia: Trata-se de uma revisão integrativa realizada no ano de 2019, em bases de dados nacionais e internacionais. Resultados: Foram encontrados 17 artigos, com sete instrumentos utilizados para avaliar a qualidade de vida de pessoas com estomias intestinais: City of Hope Quality of Life-Ostomy Questionnaire, Stoma Self-Efficacy Scale, World Health Organization Quality of Life abreviado, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Ostomy-specific (Stoma-QoL) e Escala de Qualidade de Vida de Flanagan. Conclusão: Esta revisão permitiu identificar os instrumentos que estão sendo utilizados para avaliar a QV de pessoas com estomias intestinais. Após a análise dos instrumentos, salienta-se que o City of Hope – Quality of Life – Ostomy Questionnaire é o mais abrangente dentre os instrumentos específicos às pessoas com estomias intestinais.


2016 ◽  
Vol 9 (1) ◽  
pp. 85-89
Author(s):  
Svetlana A. Mateva ◽  
Margarita R. Nikolova ◽  
Alexandar V. Valkov ◽  
Margarita R. Nikolova

Summary Liposarcoma is one of the most common soft tissue sarcomas in adults with a relative incidence amongst other sarcomas ranging from 9.8% to 16%. It usually locates in the limbs and retroperitoneum. Primary liposarcomas of the larynx and hypopharynx are rare, comprising less than 20% of all head and neck liposarcomas. According to World Health Organization, these tumors are divided into four histologic types, and well-differentiated liposarcoma is the most common one. It is a tumor of low-grade malignancy that may recur locally, but does not metastasize. We present a case of laryngopharyngeal well- differentiated liposarcoma in an old patient with two previous removals. We also discuss recently published cases with this unusual location of liposarcoma.


Author(s):  
Martin C. Tom ◽  
Daniel P. Cahill ◽  
Jan C. Buckner ◽  
Jörg Dietrich ◽  
Michael W. Parsons ◽  
...  

Following the identification of key molecular alterations that provided superior prognostication and led to the updated 2016 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification, the understanding of glioma behavior has rapidly evolved. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 are present in the majority of adult grade 2 and 3 gliomas, and when used in conjunction with 1p/19q codeletion for classification, the prognostic distinction between grade 2 versus grade 3 is diminished. As such, the previously often used term of “low-grade glioma,” which referred to grade 2 gliomas, has now been replaced by the phrase “lower-grade glioma” to encompass both grade 2 and 3 tumors. Additional molecular characterization is ongoing to even further classify this heterogeneous group of tumors. With such a colossal shift in the understanding of lower-grade gliomas, management of disease is being redefined in the setting of emerging molecular-genetic biomarkers. In this article, we review recent progress and future directions regarding the surgical, radiotherapeutic, chemotherapeutic, and long-term management of adult lower-grade gliomas.


2018 ◽  
Vol 143 (5) ◽  
pp. 643-647 ◽  
Author(s):  
Tsung-Heng Tsai ◽  
Wen-Ying Lee

Succinate dehydrogenase (SDH)–deficient renal cell carcinoma is a recently recognized distinct subtype of renal cell carcinoma in the 2016 World Health Organization classification. It is associated with SDH gene germline mutations, which also cause paraganglioma/pheochromocytoma, gastrointestinal stromal tumor, and pituitary adenoma. The tumor most commonly presents in young adulthood. The tumors are arranged in solid nests or in tubules and frequently show cystic change. The tumors are composed of cuboidal to oval cells with round nuclei, dispersed chromatin, and inconspicuous nucleoli. The cytoplasm is eosinophilic or flocculent but not truly oncocytic. The most distinctive histologic feature is the presence of cytoplasmic vacuoles or inclusions. Loss of SDH subunit B immunostaining is needed for a definite diagnosis. The prognosis is good for low-grade tumors but worse for tumors with high-grade nuclei, sarcomatoid change, or coagulative necrosis. Long-term follow-up is indicated.


2019 ◽  
Vol 63 (3) ◽  
pp. 224-232
Author(s):  
Ludmila Barbosa de Souza Balsimelli ◽  
Jamille Costa de Oliveira ◽  
Flora Ávila Adorno ◽  
Clarissa Almeida Brites ◽  
Giuliano Stefanello Bublitz ◽  
...  

Objective: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. Study Design: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. Results: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. Conclusions: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.


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