Reprint: Peculiarities of expression of apoptosis markers in the tissues of primary fallopian tubes carcinoma

Aim: immunohistochemical analysis of apoptosis markers in the tissue of PFTC. Introduction: Primary fallopian tubes carcinoma is a rare case among oncological diseases of female genital organs, but the mortality rate is rather high. Nowadays, the prognostic factors of this neoplasia are not fully determined. The data on the p53 and bcl2 proteins expression and their use as prognostic factors in patients with malignant tumors of many locations are contradictory. Methods: the study was conducted on 66 samples of fallopian tubes tumor tissue. To study the apoptosis peculiarities of tumor cells the mouse monoclonal antibodies for bcl-2 (clone 100/D5) and p53 (clone SP5) were used. Mathematic calculations were done using Microsoft Excel 2010 with AtteStat 12.0.5. Results: The high expression of p53 was found in patients of all clinical stages. Mutations of p53 increased with spreading of the neoplastic process. Strong correlation of p53 presence in tumor samples and clinical stage of the disease was determined (r=0.77). In contrast to the abovementioned protein the study of bcl-2 showed the moderate negative correlation between this protein and the stage of the disease (r=−0.54). Analysis of the dependence of p53 expression with the presence or absence of lymph nodes metastasis showed a direct correlation between the indicators (r=0.25). Thus the level of p53 expression in patients with N1 was 80.6±2.7% compared with the N0 group (29.7±3.6%). The stage of neoplasia differentiation is in moderate direct correlation with p53 expression (r=0.58) and in inverse with – bcl-2 (r=−0.64). Conclusion: Expression of p53 depends on neoplasia spreading and stage of tumor differentiation. The expression of p53 is an independent prognostic marker for N-status and helps to classify the patients into “risk” groups.

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N6-methyladenosine-related non-coding RNAs are potential prognostic and immunotherapeutic responsiveness biomarkers for bladder cancer

The EPMA Journal ◽

10.1007/s13167-021-00259-w ◽

2021 ◽

Author(s):

Miaolong Lu ◽

Hailun Zhan ◽

Bolong Liu ◽

Dongyang Li ◽

Wenbiao Li ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Prognostic Factors ◽

Risk Model ◽

Clinical Stage ◽

Risk Groups ◽

Lasso Regression ◽

Prognostic Evaluation ◽

Non Coding Rnas ◽

Tcga Dataset

Abstract Background Bladder cancer (BC) is a commonly occurring malignant tumor of the urinary system, demonstrating high global morbidity and mortality rates. BC currently lacks widely accepted biomarkers and its predictive, preventive, and personalized medicine (PPPM) is still unsatisfactory. N6-methyladenosine (m6A) modification and non-coding RNAs (ncRNAs) have been shown to be effective prognostic and immunotherapeutic responsiveness biomarkers and contribute to PPPM for various tumors. However, their role in BC remains unclear. Methods m6A-related ncRNAs (lncRNAs and miRNAs) were identified through a comprehensive analysis of TCGA, starBase, and m6A2Target databases. Using TCGA dataset (training set), univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop an m6A-related ncRNA–based prognostic risk model. Kaplan-Meier analysis of overall survival (OS) and receiver operating characteristic (ROC) curves were used to verify the prognostic evaluation power of the risk model in the GSE154261 dataset (testing set) from Gene Expression Omnibus (GEO). A nomogram containing independent prognostic factors was developed. Differences in BC clinical characteristics, m6A regulators, m6A-related ncRNAs, gene expression patterns, and differentially expressed genes (DEGs)–associated molecular networks between the high- and low-risk groups in TCGA dataset were also analyzed. Additionally, the potential applicability of the risk model in the prediction of immunotherapeutic responsiveness was evaluated based on the “IMvigor210CoreBiologies” data set. Results We identified 183 m6A-related ncRNAs, of which 14 were related to OS. LASSO regression analysis was further used to develop a prognostic risk model that included 10 m6A-related ncRNAs (BAALC-AS1, MIR324, MIR191, MIR25, AC023509.1, AL021707.1, AC026362.1, GATA2-AS1, AC012065.2, and HCP5). The risk model showed an excellent prognostic evaluation performance in both TCGA and GSE154261 datasets, with ROC curve areas under the curve (AUC) of 0.62 and 0.83, respectively. A nomogram containing 3 independent prognostic factors (risk score, age, and clinical stage) was developed and was found to demonstrate high prognostic prediction accuracy (AUC = 0.83). Moreover, the risk model could also predict BC progression. A higher risk score indicated a higher pathological grade and clinical stage. We identified 1058 DEGs between the high- and low-risk groups in TCGA dataset; these DEGs were involved in 3 molecular network systems, i.e., cellular immune response, cell adhesion, and cellular biological metabolism. Furthermore, the expression levels of 8 m6A regulators and 12 m6A-related ncRNAs were significantly different between the two groups. Finally, this risk model could be used to predict immunotherapeutic responses. Conclusion Our study is the first to explore the potential application value of m6A-related ncRNAs in BC. The m6A-related ncRNA–based risk model demonstrated excellent performance in predicting prognosis and immunotherapeutic responsiveness. Based on this model, in addition to identifying high-risk patients early to provide them with focused attention and targeted prevention, we can also select beneficiaries of immunotherapy to deliver personalized medical services. Furthermore, the m6A-related ncRNAs could elucidate the molecular mechanisms of BC and lead to a new direction for the improvement of PPPM for BC.

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Expression of bcl-2 in Classical Hodgkin's Lymphoma: An Independent Predictor of Poor Outcome

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.358 ◽

2005 ◽

Vol 23 (16) ◽

pp. 3773-3779 ◽

Cited By ~ 41

Author(s):

Stephen J. Sup ◽

Carlos A. Alemañy ◽

Brad Pohlman ◽

Paul Elson ◽

Serena Malhi ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Prognostic Score ◽

Univariate Analysis ◽

Risk Groups ◽

Tissue Microarrays ◽

Hodgkin's Lymphoma ◽

Stage Iii ◽

Primary Therapy ◽

P53 Expression ◽

Independent Prognostic Marker

Purpose Although most classical Hodgkin's lymphoma (CHL) patients are cured, a significant minority fails primary therapy and may die as a result of their disease. Age, stage, and other basic clinical and laboratory parameters, which comprise the International Prognostic Score (IPS), are used at diagnosis to predict outcome. To date, there is no consensus on biologic markers that add value to these parameters. Patients and Methods We evaluated 107 CHL patients for bcl-2, p53, and p21 expression by immunohistochemistry using tissue microarrays and correlated the results with outcome. The median follow-up of the 79 surviving patients was 6.8 years. Results Univariate analysis showed that age ≥ 45 years, stage III or IV, and IPS ≥ 3 were associated with a poor failure-free survival (FFS) and overall survival (OS). bcl-2 was expressed in 26% of patients and was associated with poor FFS and a trend for OS. p53 expression in combination with lack of p21 expression was not associated with outcome. Multivariate analysis showed that three factors were independently associated with both FFS and OS: age ≥ 45 years, stage III or IV, and bcl-2 expression. Using these three parameters, a scoring system was devised that stratified patients into three risk groups (with zero, one, or two to three of these risk factors) and a progressively worse FFS and OS (P < .001). Conclusion Expression of bcl-2 in CHL is a useful, independent prognostic marker and can be used in association with clinical parameters to identify newly diagnosed patients with a good, intermediate, or poor prognosis.

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(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder

Cancers ◽

10.3390/cancers13225642 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5642

Author(s):

Gorka Larrinaga ◽

Julio Calvete-Candenas ◽

Jon Danel Solano-Iturri ◽

Ana M. Martín ◽

Angel Pueyo ◽

...

Keyword(s):

Prognostic Factors ◽

Cox Regression ◽

Prognostic Role ◽

Primary Tumors ◽

P53 Expression ◽

Erk Activation ◽

Independent Prognostic Marker ◽

Comorbidity Index ◽

Carcinoma Of The Bladder ◽

First Time

(Pro)renin receptor (PRR) is being investigated in several malignancies as it activates pathogenic pathways that contribute to cell proliferation, immunosuppressive microenvironments, and acquisition of aggressive neoplastic phenotypes. Its implication in urothelial cancer (UC) has not been evaluated so far. We retrospectively evaluate the prognostic role of PRR expression in a series of patients with invasive UC treated with radical cystectomy and other clinical and histopathological parameters including p53, markers of immune-checkpoint inhibition, and basal and luminal phenotypes evaluated by tissue microarray. Cox regression analyses using stepwise selection evaluated candidate prognostic factors and disease-specific survival. PRR was expressed in 77.3% of the primary tumors and in 70% of positive lymph nodes. PRR expression correlated with age (p = 0.006) and was associated with lower preoperatively hemoglobin levels. No other statistical association was evidenced with clinical and pathological variables (gender, ASA score, Charlson comorbidity index, grade, pT, pN) or immunohistochemical expressions evaluated (CK20, GA-TA3, CK5/6, CD44, PD-L1, PD-1, B7-H3, VISTA, and p53). PRR expression in primary tumors was associated with worse survival (log-rank, p = 0.008). Cox regression revealed that PRR expression (HR 1.85, 95% CI 1.22–2.8), pT (HR 7.02, 95% CI 2.68–18.39), pN (HR 2.3, 95% CI 1.27–4.19), and p53 expression (HR 1.95, 95% CI 1.1–3.45) were independent prognostic factors in this series. In conclusion, we describe PRR protein and its prognostic role in invasive UC for the first time. Likely mechanisms involved are MAPK/ERK activation, Wnt/β-catenin signaling, and v-ATPAse function.

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A Study on the Prognostic Factors in Surgical Cases of Malignant Tumors of the Skull Base

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0032-1314246 ◽

2012 ◽

Vol 73 (S 02) ◽

Author(s):

T. Asakage ◽

Y. Ebihara ◽

Y. Saito ◽

G. Omura ◽

K. Kawai ◽

...

Keyword(s):

Prognostic Factors ◽

Skull Base ◽

Malignant Tumors

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PROSPECTS OF ARTIFICIAL INTELLIGENCE IN CARRYING OUT THE ONCOLOGICAL COMPONENT OF MEDICAL EXAMINATION OF THE POPULATION

Problems in oncology ◽

10.37469/0507-3758-2019-65-2-234-237 ◽

2019 ◽

Vol 65 (2) ◽

pp. 234-237

Author(s):

Vyacheslav Cherenkov ◽

A. Petrov ◽

I. Gulkov ◽

A. Kostyukov

Keyword(s):

Artificial Intelligence ◽

Early Diagnosis ◽

Mass Screening ◽

Malignant Tumors ◽

Risk Groups ◽

Modern World ◽

Pilot Program ◽

Urgent Problem ◽

Gender And Age ◽

Group Version

Diagnosis of malignant tumors is an urgent problem of the modern world. Early diagnosis depends on General practitioners. The doctor should conduct a systematic examination of the patient regularly, taking into account the risk groups, gender and age. With mass screening, signs of dysplasia or an early focus, developing cancer can «slip away» [1]. Optimization of analysis and examination algorithms is required, which is not always possible for one person. Positive application of the digital program with elements of imaging in Oncology, we were able to create such a class of tasks for the preliminary subjective-objective survey of patients in three versions: with a widescreen screen and consoles for patients (group version up to 15 or more patients), interactive (touch) and tablet. The results of the survey are sent through the accepted channels to the doctor with recommendations for further examination, and the patient is given a coupon. The pilot program showed that the system of such robotic technologies in the future can replace the oncologist in its development to artificial intelligence at the stage of the primary link.

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Radiomics and Dosiomics for Predicting Local Control after Carbon-Ion Radiotherapy in Skull-Base Chordoma

Cancers ◽

10.3390/cancers13020339 ◽

2021 ◽

Vol 13 (2) ◽

pp. 339

Author(s):

Giulia Buizza ◽

Chiara Paganelli ◽

Emma D’Ippolito ◽

Giulia Fontana ◽

Silvia Molinelli ◽

...

Keyword(s):

Prognostic Factors ◽

Skull Base ◽

Local Control ◽

Tumour Progression ◽

Risk Groups ◽

Carbon Ion Radiotherapy ◽

Survival Models ◽

Carbon Ion ◽

Combined Models ◽

Skull Base Chordoma

Skull-base chordoma (SBC) can be treated with carbon ion radiotherapy (CIRT) to improve local control (LC). The study aimed to explore the role of multi-parametric radiomic, dosiomic and clinical features as prognostic factors for LC in SBC patients undergoing CIRT. Before CIRT, 57 patients underwent MR and CT imaging, from which tumour contours and dose maps were obtained. MRI and CT-based radiomic, and dosiomic features were selected and fed to two survival models, singularly or by combining them with clinical factors. Adverse LC was given by in-field recurrence or tumour progression. The dataset was split in development and test sets and the models’ performance evaluated using the concordance index (C-index). Patients were then assigned a low- or high-risk score. Survival curves were estimated, and risk groups compared through log-rank tests (after Bonferroni correction α = 0.0083). The best performing models were built on features describing tumour shape and dosiomic heterogeneity (median/interquartile range validation C-index: 0.80/024 and 0.79/0.26), followed by combined (0.73/0.30 and 0.75/0.27) and CT-based models (0.77/0.24 and 0.64/0.28). Dosiomic and combined models could consistently stratify patients in two significantly different groups. Dosiomic and multi-parametric radiomic features showed to be promising prognostic factors for LC in SBC treated with CIRT.

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Aspartame and cancer – new evidence for causation

Environmental Health ◽

10.1186/s12940-021-00725-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Philip J. Landrigan ◽

Kurt Straif

Keyword(s):

Public Health ◽

Cancer Risk ◽

Malignant Tumors ◽

Daily Intake ◽

Immunohistochemical Analysis ◽

International Agency ◽

Advisory Group ◽

Malignant Neoplasms ◽

Acceptable Daily Intake ◽

New Findings

Abstract Background Aspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. Methods To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. Findings This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. Interpretation These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.

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Identification of Prognostic RBPs in Osteosarcoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211004918 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110049

Author(s):

Bei Li ◽

Long Fang ◽

Baolong Wang ◽

Zengkun Yang ◽

Tingbao Zhao

Keyword(s):

Regression Analysis ◽

Prognostic Factors ◽

Differential Expression ◽

Ribosome Biogenesis ◽

Rna Binding ◽

Cox Regression ◽

Rna Binding Proteins ◽

Malignant Tumors ◽

Differential Expression Analysis ◽

Cox Regression Analysis

Osteosarcoma often occurs in children and adolescents and causes poor prognosis. The role of RNA-binding proteins (RBPs) in malignant tumors has been elucidated in recent years. Our study aims to identify key RBPs in osteosarcoma that could be prognostic factors and treatment targets. GSE33382 dataset was downloaded from Gene Expression Omnibus (GEO) database. RBPs extraction and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological function of differential expression RBPs. Moreover, we constructed Protein-protein interaction (PPI) network and obtained key modules. Key RBPs were identified by univariate Cox regression analysis and multiple stepwise Cox regression analysis combined with the clinical information from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Risk score model was generated and validated by GSE16091 dataset. A total of 38 differential expression RBPs was identified. Go and KEGG results indicated these RBPs were significantly involved in ribosome biogenesis and mRNA surveillance pathway. COX regression analysis showed DDX24, DDX21, WARS and IGF2BP2 could be prognostic factors in osteosarcoma. Spearman’s correlation analysis suggested that WARS might be important in osteosarcoma immune infiltration. In conclusion, DDX24, DDX21, WARS and IGF2BP2 might play key role in osteosarcoma, which could be therapuetic targets for osteosarcoma treatment.

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Tumor-Infiltrating CD20+ B Lymphocytes: Significance and Prognostic Implications in Oral Cancer Microenvironment

Cancers ◽

10.3390/cancers13030395 ◽

2021 ◽

Vol 13 (3) ◽

pp. 395

Author(s):

Faustino Julián Suárez-Sánchez ◽

Paloma Lequerica-Fernández ◽

Juan Pablo Rodrigo ◽

Francisco Hermida-Prado ◽

Julián Suárez-Canto ◽

...

Keyword(s):

B Lymphocytes ◽

Clinical Stage ◽

Inverse Correlation ◽

Tumor Infiltrating Lymphocytes ◽

Immunohistochemical Analysis ◽

Second Primary ◽

Strong Positive Correlation ◽

Related Factors ◽

Primary Tumors ◽

Sox2 Expression

Immunohistochemical analysis of stromal/tumoral CD20+ B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20+ B lymphocytes and other immune profiles (i.e., CD4+, CD8+, and FOXP3+ TILs, and CD68+ and CD163+ macrophages) both in stroma and tumor nests. Strikingly, CD20+ TILs were inversely correlated with NANOG/SOX2 expression. Stromal CD20+ TILs were significantly associated with T classification and second primary tumors. A stratified survival analysis showed that tumoral CD20+ TILs were significantly associated with prognosis in male and younger patients, with tobacco or alcohol consumption, high tumoral CD8+ TILs, low tumoral infiltration by CD68+ macrophages, positive PD-L1 expression, and negative NANOG/SOX2. Multivariate Cox analysis further revealed clinical stage and tumoral CD20+ TILs independently associated with disease-specific survival (HR = 2.42, p = 0.003; and HR = 0.57, p = 0.04, respectively). In conclusion, high CD20+ TIL density emerges as an independent good prognostic factor in OSCC, suggesting a role in antitumor immunity. This study also uncovered an inverse correlation between CD20+ TILs and CSC marker expression.

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Esophageal Small Cell Carcinomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-0228-escc ◽

2000 ◽

Vol 124 (2) ◽

pp. 228-233 ◽

Cited By ~ 3

Author(s):

King Y. Lam ◽

Simon Law ◽

Peter H. M. Tung ◽

John Wong

Keyword(s):

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Survival Data ◽

Malignant Tumors ◽

P53 Protein ◽

Small Cell ◽

Immunohistochemical Method ◽

Clinicopathologic Features ◽

P53 Expression ◽

Mib 1

Abstract Objective.—To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma. Method.—Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made. Results.—Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810–964) positive cells per 1000. Overall median survival was 3.4 months. In patients who underwent chemotherapy, there was significant response. Conclusions.—Esophageal small cell carcinoma is an aggressive tumor. Overexpression of p53 is associated with early stages of carcinogenesis. The high proliferative index, as defined by the MIB-1 immunohistochemical method, may be related to aggressive behavior and high sensitivity to chemotherapy and radiotherapy.

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