scholarly journals Genomic Heterogeneity of Breast Tumor Pathogenesis

2009 ◽  
Vol 3 ◽  
pp. CMO.S2946
Author(s):  
Rachel E. Ellsworth ◽  
Jeffrey A. Hooke ◽  
Craig D. Shriver ◽  
Darrell L. Ellsworth
Keyword(s):  
Current System ◽  
Treatment Options ◽  
Expression Patterns ◽  
Tumor Grade ◽  
Molecular Data ◽  
Clinical Test ◽  
Low Grade ◽  
High Grade ◽  
Breast Cancer Patients ◽  
Intermediate Grade

Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (low-grade, well-differentiated tumors) and less favorable (high-grade, poorly-differentiated tumors) outcome groups. Under the current system of tumor grading, however, a large proportion of tumors are characterized as intermediate-grade, making determination of optimal treatments difficult. In an effort to increase objectivity in the pathological assessment of tumor grade, differences in chromosomal alterations and gene expression patterns have been characterized in low-grade, intermediate-grade, and high-grade disease. In this review, we outline molecular data supporting a linear model of progression from low-grade to high-grade carcinomas, as well as contradicting genetic data suggesting that low-grade and high-grade tumors develop independently. While debate regarding specific pathways of development continues, molecular data suggest that intermediate-grade tumors do not comprise an independent disease subtype, but represent clinical and molecular hybrids between low-grade and high-grade tumors. Finally, we discuss the clinical implications associated with different pathways of development, including a new clinical test to assign grade and guide treatment options.

Correlation of pathologic tumor grade with survival in oral cavity squamous cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18557-e18557
Author(s):  
Eric Anderson ◽  
Michael Luu ◽  
Diana J. Lu ◽  
Anthony Tuan Nguyen ◽  
Jon Mallen-St. Clair ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Multivariable Analysis ◽  
Tumor Grade ◽  
Low Grade ◽  
High Grade ◽  
Intermediate Grade

e18557 Background: Pathologic tumor grade is a well-established prognostic risk factor that impacts staging and standard-of-care treatment decisions across multiple cancer types. However, the significance of tumor grade in cancers of the head and neck is less certain. Even in oral cavity squamous cell carcinoma (OCSCC), the head and neck cancer subsite with largest body of literature regarding the predictive value of tumor grade is, the prognostic significance of tumor grade remains controversial. Thus, we sought to better elucidate the prognostic importance of tumor grade in OCSCC. Methods: Patients with OCSCC diagnosed from 2004-2015 and undergoing primary surgery with or without adjuvant treatment in the National Cancer Data Base (NCDB) were identified. Overall survival (OS) was estimated using the Kaplan-Meier method with and without propensity score matching (PSM). Univariate and multivariable survival analyses were performed using Cox regression. Analyses were adjusted for multiple clinicopathologic factors, including age, sex, comorbidity status, year of diagnosis, pathologic staging, margin status, number of lymph nodes (LN) examined/positive, extranodal extension (ENE), lymphovascular invasion (LVI), adjuvant radiation, and concomitant chemotherapy. Results: Median follow-up was 40.7 months. Of 13,941 patients with OCSCC, 2,883 had low-grade tumors, 8,716 had intermediate-grade tumors, and 2,342 had high-grade tumors. Higher tumor grade was strongly associated with decreased survival. Specifically, five year OS was 62.7%, 52.8%, and 42.5% in low-grade (LG), intermediate-grade (IG), and high-grade (HG) OCSCC, respectively (p-value < 0.001). In PSM cohorts, OCSCC patients with high-grade had significantly worse 5 year OS (47.7% vs. 57.7%, p < 0.001) in comparison to those with LG OCSCC. Similarly, patients with IG tumors has worse 5-year OS (55.6% vs. 60.3%, p = 0.001) than patients with LG tumors in PSM cohorts. In multivariable analysis, both HG (HR 1.38, 95% CI 1.25-1.52, p < 0.001) and IG (HR 1.17, 95% CI 1.08-1.26, p < 0.001) OCSCC was associated with worse survival than what was observed in LG tumors. The magnitude of the independent effect of tumor grade in multivariable analysis was greater than or equal to what was observed with other well-established prognostic factors like margin positivity (HR 1.34), ENE (HR 1.35), and LVI (HR 1.18). Conclusions: Pathologic tumor grade is a strong predictor of survival among patients with OCSCC. Tumor grade should be considered when making therapeutic recommendations for OCSCC.

scholarly journals CBIO-16. SUPPRESSION OF HISTONE H3.3 MITOTIC PHOSPHORYLATION DRIVES DEVELOPMENT OF H3K27M-MUTANT DIFFUSE MIDLINE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii18-ii19
Author(s):  
Charles Day ◽  
Alyssa Langfald ◽  
Florina Grigore ◽  
Leslie Sepaniac ◽  
Jason Stumpff ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Treatment Options ◽  
Chromosome Instability ◽  
Pericentromeric Heterochromatin ◽  
Low Grade ◽  
High Grade ◽  
Chromosome Missegregation ◽  
Mitotic Phosphorylation ◽  
Chk1 Kinase

Abstract Pediatric midline gliomas – including DIPG – are lethal brain tumors in children, with poor prognosis and limited treatment options that provide only short-term benefits. The majority have a lysine-to-methionine substitution at residue 27 (H3K27M) in genes expressing histone H3 – predominantly in the H3.3 variant. This causes a global reduction in H3 Lys27 tri-methylation (H3K27Me3), comprehensive epigenetic reprogramming, and is a key driver in gliomagenesis. We show that the H3.3K27M mutation also induces chromosome segregation defects, which in high-grade tumors, results in extensive copy number alterations (CNAs). Ser31 is one of five amino acid substitutions differentiating H3.3 from canonical H3.1. Mitotic phosphorylation of H3.3 Ser31 by Chk1 kinase is restricted to pericentromeric heterochromatin, where it plays a role in chromosome segregation. We show that the K27M mutation affects neighboring Ser31 phosphorylation and pericentromeric heterochromatin organization. We demonstrate that (i) H3.3 K27M protein is defective for Ser31 phosphorylation by Chk1 kinase in vitro; (ii) DIPG cell lines have significantly decreased mitotic Ser31 phosphorylation, and are chromosomally unstable; and (iii) CRISPR-reversion of H3.3K27M to Lys27 restores phospho-Ser31 (and Lys27 tri-methylation) and significantly decreases chromosome instability. Expression of H3.3K27M or non-phosphorylatable H3.3S31A mutants in WT cells results in chromosome missegregation; this is suppressed by co-expression of phospho-mimetic H3.3K27M/S31E. In normal cells, chromosome missegregation stimulates p53-dependent cell cycle arrest in G1 to prevent the proliferation of aneuploid daughters. However, cells expressing H3.3 K27M or S31A failed to arrest following missegregation - despite having WT p53. Finally, in a novel mouse model of glioma, mean survival of mice with tumors induced with H3.3K27M and H3.3S31A was 81 and 68 days: 100% of H3.3S31A mice developed high-grade tumors. H3.3 WT controls developed only low-grade tumors and all survived 100 days. H3.3S31A is WT for Lys27 tri-methylation and thus, loss of Ser31 phosphorylation alone is oncogenic.

scholarly journals Soluble cytotoxic T-lymphocyte–associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiajia Liu ◽  
Xiaoyi Tian ◽  
Yan Wang ◽  
Xixiong Kang ◽  
Wenqi Song
Keyword(s):  
T Lymphocyte ◽  
Roc Curve ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Grade ◽  
Curve Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
High Grade ◽  
Healthy Individuals ◽  
Roc Curve Analysis

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.

Mucoepidermoid Carcinomas of the Larynx

2022 ◽  
pp. 000348942110694
Author(s):  
Holden W. Richards ◽  
Caitlin Bertelsen ◽  
Bronwyn Hamilton ◽  
David Sauer ◽  
Joshua Schindler
Keyword(s):  
Radiation Therapy ◽  
Radical Neck Dissection ◽  
Case Series ◽  
Tumor Grade ◽  
Tertiary Hospital ◽  
Additional Treatment ◽  
Partial Laryngectomy ◽  
High Grade ◽  
Intermediate Grade ◽  
Postoperative Radiation Therapy

Objectives: Discussions regarding the specific management and outcomes for laryngeal MEC are limited to very small, single-institution case series. To look further into the diagnosis and management of these uncommon non-squamous cell carcinomas of the larynx, we present 3 recent cases of laryngeal MEC treated at our institution. Methods: Patients at a tertiary hospital treated for MEC between October 2019 and December 2020 were retrospectively identified. Chart review, imaging analysis, and histologic slide creation were completed for all patients. Results: We identified and treated 2 patients with high-grade supraglottic and 1 patient with intermediate-grade glottic MEC. These patients presented to our clinic with a primary complaint of either gradual, worsening dysphonia, dysphagia, or both. All patients underwent laryngovideostroboscopy as well as panendoscopy with directed submucosal biopsy, which was consistent with MEC. MRI was performed in 2 of the cases further elucidating the extent of submucosal spread. PET-CT was performed in all 3 cases, and none demonstrated evidence of regional or distal metastases. Surgically, high-grade MEC lesions were treated with a total laryngectomy. The intermediate MEC lesion was managed with a supracricoid partial laryngectomy (SCPL). Surgical margins were free of tumor in all cases with no nodal metastases by modified radical neck dissection. Radiation therapy was offered to both high-grade MEC patients and declined by one. Radiation was not recommended to the patient with intermediate-grade MEC as we believed that the risk of additional treatment outweighed the benefit. Conclusion: We believe that MEC of the larynx should be considered in patients with atypical submucosal laryngeal masses. Laryngovideostroboscopy, MRI, and PET imaging may be valuable in determining the extent of the lesions and planning appropriate surgery. Postoperative radiation therapy should be considered a per tumor grade in other more studied sites, as there is no data on efficacy in laryngeal MEC.

scholarly journals Prognostic factors in non-Hodgkin lymphomas

2000 ◽  
Vol 118 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Karin Zattar Cecyn ◽  
José Salvador Rodrigues de Oliveira ◽  
Antônio Correia Alves ◽  
Maria Regina Regis Silva ◽  
José Kerbauy
Keyword(s):  
Prognostic Factors ◽  
Hodgkin Lymphoma ◽  
Low Grade ◽  
High Grade ◽  
Cns Involvement ◽  
Intermediate Grade ◽  
Non Hodgkin Lymphoma ◽  
Tumor Dissemination ◽  
Mediastinal Disease ◽  
Extranodal Disease

CONTEXT: In Hodgkin's disease, each clinical or pathologic stage can be related to the extent of the area involved and predicts the next anatomical region at risk for tumor dissemination. OBJECTIVE: To determine the best prognostic factors that could predict survival in non-Hodgkin lymphoma cases. DESIGN: A retrospective study. LOCATION: Department of Hematology and Transfusion Medicine, Universidade Federal de São Paulo - Escola Paulista de Medicina. PARTICIPANTS: 142 patients with non-Hodgkin lymphoma diagnosed between February 1988 and March 1993. MAIN MEASUREMENTS: Histological subset, Sex, Age, Race, B symptoms, Performance status, Stage, Extranodal disease, Bulk disease, Mediastinal disease, CNS involvement, BM infiltration, Level of DHL, Immunophenotype. RESULTS: In the first study (113 patients), the following variables had a worse influence on survival: yellow race (P<0.1); ECOG II, III e IV (P<0.1) and extranodal disease (P<0.1) for high grade lymphomas; constitutional symptoms (P<0.1), ECOG II, III e IV (P<0.1) and involvement of CNS (P<0.1) for intermediate grade and the subtype lymphoplasmocytoid (P=0.0186) for low grade lymphomas. In the second survey (93 patients), when treatment was included, the variables related to NHL survival were: CNS involvement (P<0.1) for high grade lymphomas, constitutional symptoms (P<0.1), ECOG II, III, IV (P=0.0185) and also CNS involvement (P<0.1) for the intermediate group. There were no variables related to the survival for low-grade lymphomas. CONCLUSIONS: The intermediate grade lymphomas were more compatible with data found in the literature, probably because of the larger number of patients. In this specific case, the treatment did not have an influence on the survival.

scholarly journals Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan-cancer transcriptome analysis of a distinct entity

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Huang ◽  
Fei Ren ◽  
Shujuan Ni ◽  
Cong Tan ◽  
Weiwei Weng ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Expression Patterns ◽  
Biological Behavior ◽  
Low Grade ◽  
High Grade ◽  
Clinicopathologic Characteristics ◽  
Signet Ring ◽  
Cancer Transcriptome ◽  
Male Patients ◽  
Pan Cancer

Abstract Background and aim Amphicrine carcinoma, in which endocrine and epithelial cell constituents are present within the same cell, is very rare. This study characterized the clinicopathologic and survival analysis of this tumor, further compared the genetic diversities among amphicrine carcinoma and other tumors. Materials and methods The clinicopathologic characteristics and survival outcomes of amphicrine carcinoma in this study were analyzed. The pan-cancer transcriptome assay was utilized to compare the genetic expression profile of this entity with that of conventional adenocarcinoma or neuroendocrine tumors. Results Ten cases (all in male patients) were identified in the stomach or intestine, with a median patient age of 62 years. There were characteristic patterns in the tumors: tubular, fusion or single-file growth of goblet- or signet ring-like cells. Four tumors were classified as low-grade and 6 as high-grade according to the histologic architecture. All cases were positive for neuroendocrine markers (synaptophysin and chromogranin A) and showed intracellular mucin in the amphicrine components. Four cases exhibited mRNA expression patterns showing transcriptional homogeneity with conventional adenocarcinomas and genetic diversity from neuroendocrine tumors. During the follow-up period, 3 patients died of disease, all of whom had high-grade tumors. Patients with high-grade amphicrine carcinoma had worse outcomes than those with low-grade tumors. Conclusions This study confirms the morphological, immunostaining and transcriptome alterations in amphicrine carcinoma distinct from those in conventional adenocarcinomas and neuroendocrine tumors, but additional studies are warranted to determine the biological behavior and therapeutic response.

MOLECULAR MARKERS IN OSTEOSARCOMA – A cDNA MICROARRAY AND RT-PCR ANALYSIS

2005 ◽  
Vol 09 (02) ◽  
pp. 77-84
Author(s):  
Meera R. Hameed ◽  
Tao-Zhen Lin ◽  
Frederick Coffman ◽  
Marion C. Cohen ◽  
Helen Fernandes ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Cdna Microarray ◽  
Expression Patterns ◽  
Bone Neoplasms ◽  
Poor Response ◽  
Pcr Analysis ◽  
Low Grade ◽  
High Grade ◽  
Cdna Microarray Analysis ◽  
Response To Chemotherapy

Osteosarcomas account for about 20% of all primary bone neoplasms, and affect predominantly adolescents. Important prognostic factors include the presence or absence of metastases at the time of presentation and tumor response to neoadjuvant chemotherapy. Biological markers predicting metastases and chemoresistance are not well characterized. cDNA microarray analysis enables one to examine the expression of thousands of genes in tumor samples. We performed cDNA microarray analysis of histologically low and high grade areas in osteosarcomas to identify gene expression patterns which may depict aggressive behavior. Microarray analysis with 1.2 K cancer array revealed many differentially expressed genes (both upregulated and downregulated), in histologically high grade tumor samples as compared with a low grade sample. Selected up and down regulated markers in the high grade sarcomas were tested in a group of high grade osteosarcomnas (OS) with varying responses to chemotherapy. Of the multiple markers analyzed, ezrin, a member of the ERM family of membrane-cytoskeleton linkers showed an expression pattern statistically significant between tumors with good response to chemotherapy compared with tumors with poor response (p = 0.036). We discuss our findings, with current review of literature.

Radiotherapy of Intracranial Astrocytomas

Neurosurgery ◽  
1979 ◽  
Vol 5 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Paul W. Scanlon ◽  
William F. Taylor
Keyword(s):  
Radiation Therapy ◽  
Postoperative Radiotherapy ◽  
Tumor Grade ◽  
Low Grade ◽  
Unexpected Finding ◽  
High Grade ◽  
Death Rates ◽  
Brain Irradiation ◽  
Total Brain ◽  
Better Than

Abstract In a review of 417 intracranial astrocytomas treated radiotherapeutically at the Mayo Clinic from 1960 through 1969, the well-known correlation of tumor grade with survival was verified. Totally unexpected was the finding that age was fully as important a discriminant as tumor grade. Another unexpected finding was that patients treated with biopsy only followed by radiation therapy did as well as or slightly better than those subjected to resection followed by postoperative radiotherapy. We could not verify the importance to survival of either large dose or large volume radiotherapy, which has been emphasized by some. Patients receiving less than 1400 rets did just as well as or slightly better than those receiving more than 1400 rets. With low grade astrocytomas, survival beyond 4 years was significantly worse (higher death rates) in the group receiving more than 1400 rets. This suggested the possibility of radiation damage with delayed manifestations. We also could not verify an increased effectiveness for the generally accepted use of total brain irradiation for high grade gliomas.

Radiomics features of ground glass nodules tailored different pathological grades of lung adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23127-e23127
Author(s):  
C Zhang ◽  
Haoran Zhai ◽  
Lan He ◽  
Zai-Yi Liu ◽  
Yi-Long Wu ◽  
...  
Keyword(s):  
Smoking Status ◽  
Ground Glass ◽  
Low Grade ◽  
High Grade ◽  
Ratio Model ◽  
Intermediate Grade ◽  
Potential Predictor ◽  
Continuation Ratio ◽  
Radiomics Signature ◽  
Ground Glass Nodules

e23127 Background: Different pathological subtypes as well as different grades of adenocarcinoma based on the IASLC/ATS/ERS classification had been proven to be stage-independent predictor of survival. Radiomics features, as a novel analytic method, has been increasingly applied in variety cancer research and may be a potential predictor for preoperatively differentiating pathological grades of adenocarcinoma. Methods: Patients (pts) with radiological proved as solitary ground glass nodule were eligible in this study. Radiomics features derived from computed tomography (CT) images were extracted by Chinese Academy of Science. All pts will be categorized into three groups with lepidic predominance as low-grade, acinar and papillary predominance as intermediate-grade, micropapillary and solid predominance as high-grade. We used L1 penalized constrained continuation ratio model to select relevant radiomics features, and corresponding radiomics signature was constructed. Association between the radiomics signature and pathological grades of adenocarcinoma was explored using the Kruskal-Wallis test and C-index was performed to test the efficacy of differentiating. Results: 82 pts were included in this study. Low-grade, intermediate-grade and high-grade contained 15 (18.3%), 53 (64.6%), 14 (17.1%) pts respectively. 475 radiomics features were extracted from thin section CT image and 10 of them selected through L1 penalized constrained continuation ratio model composed radiomics signature which significantly associated with pathological grades (P < 0.0001). C-index for radiomics signature were 0.813 (95%CI 0.793-0.833). Since clinical characters including gender, age, smoking status, NSE, CEA and CYFRA21-1 were not associated with different grades of adenocarcinoma, we could not establish nomogram based on the radiomics signature and correlated clinical characters. Conclusions: Radiomics features only can be a potential predictor for preoperatively differentiating pathological grades of adenocarcinoma, which may be a more applicable clinical predictor for patients’ survival. Yet large sample sizes are warranted to confirm the results.

The nonsurgical management of upper tract urothelial carcinoma: A role for active surveillance?

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 485-485
Author(s):  
Jamil Syed ◽  
Kevin Nguyen ◽  
Juan Javier-Desloges ◽  
Michael Leapman ◽  
Jay D. Raman ◽  
...  
Keyword(s):  
Alternative Therapy ◽  
Tumor Grade ◽  
Population Based ◽  
Male Gender ◽  
Low Grade ◽  
High Grade ◽  
Upper Tract ◽  
Nonsurgical Management ◽  
Co Morbidity ◽  
Definitive Therapy

485 Background: Approximately 7% of patients with localized upper tract urothelial cancer (UTUC) are treated without definitive therapy. Understanding outcomes and alternative therapy would aid in counseling older patients with co-morbidities. Methods: We utilized the National Cancer Database to identify patients with localized UTUC managed non-surgically between 2004 and 2013. Patient demographics, co-morbidity, tumor grade, and chemotherapy and radiation utilization were recorded. Survival analyses were performed with the Kaplan-Meier method and a cox proportional hazard regression model. Results: We identified 3,157 (10.9%) patients with localized UTUC who did not receive definitive surgery. Median age was 79 years, 55% were males, 79% had government health insurance, and 68% had a CDS of 0. Tumor grade was low (grade 1 or 2) in 632 (36.4%) and high (grade 3 or 4) in 1104 (63.6%). Median overall survival (OS) for the cohort was 2.2 years, significantly shorter for patients with greater co-morbidities. Chemotherapy or radiation was performed in 294 (9.3%) and 197 (6.3%) patients respectively. There were no OS differences for individuals receiving chemotherapy. Of patients who received radiation therapy, the median OS was 1.4 vs 2.0 years, (p<0.001) favoring no radiation. Those with high grade tumors had worse survival (1.9 vs 3.8 years (p<0.001). Significant predictors of shorter OS included older age, male gender, higher CDS, and government insurance. Conclusions: In this population-based cohort, 10.9% of patients with localized UTUC were managed non-surgically. Radiation and chemotherapy were not routinely utilized, and did not demonstrate improved survival. Median OS was significantly shorter for those with higher grade disease, increasing co-morbidity profile, male gender, and those with government insurance status.

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