Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

Pattern of Cytogenetic Abnormality by Fluorescence in Situ Hybridization (FISH) in Multiple Myeloma Patients in a Tertiary Hospital

Background: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance, with survival duration ranging from a few months to more than 10 years. Cytogenetic abnormalities (CA) detected by fluorescence in situ hybridization (FISH) are of major prognostic significance since e.g. patients with del(17p), t(4;14) or gain 1q21 show dismal outcome. Objective: To evaluate the cytogenetic patterns by fluorescence in situ hybridization (FISH) of clinically diagnosed cases of multiple myeloma.Methods:This cross-sectional study was conducted in Department of Haematology, Dhaka Medical College Hospital, Dhaka, from January 2018 to December 2018. A total number of 30 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 10.0.Results:Out of 30 diagnosed Multiple Myeloma cases the mean age was 56.37±10.38 years and male to female ratio was almost 3:1. Sixteen (56.7%) of 30 patients. Among 30 cases of 8 cases were thyrogenicity positive of 7(23.3%) patients was detected del 13q positive. Isolated del 13q was found in 4 cases. 2 cases were found coexistence of del 13q and del 17p positive ;1 case was found coexistence of del 13q and t(4;14) positive and rest of 1 case had del 17 p positive. There was no detectable t (11; 14) and t(14;16) in any of 30 cases.Conclusion:FISH panel for Multiple Myeloma including del (13q); t(11;14); t(4;14), del(17p), t(14;16) is very important molecular test for the prognosis , risk stratification, treatment modality of the patient. On the basis of cytogenetic abnormality Multiple Myeloma risk stratification is modified now a day. This Revised International Staging system R-ISS is a simple and powerful prognostic staging system.

Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

Tumor Reduction in Multiple Myeloma: New Concepts for New Therapeutics

The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years.

Comprehensive bioinformatic analysis of the expression and prognostic significance of TSC22D domain family genes in acute myeloid leukemia

Background: TSC22D domain family genes, including Tsc22d1-4, have been extensively reported to be involved in tumors. However, their expression profiles and prognostic significance in acute myeloid leukemia (AML) remain unknown. Methods: The present study investigated the expression profiles and prognostic significance of TSC22D domain family genes in AML through the use of multiple online databases, including the CCLE, EMBL-EBI, HPA, Oncomine,GEPIA2, UALCAN, BloodSpot, and GSCALite databases. The cBioPortal and GSCALite databases were used to explore the genetic alteration and copy number variation (CNV) of the Tsc22d3 gene. The TRRUST (Version 2) database was used to explore the gene ontology biological process, disease ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with the Tsc22d3 gene. The AnimalTFDB3.0, STRING, and Harmonizome databases were used to investigate the protein–protein interaction (PPI) network of the Tsc22d3 gene. The Harmonizome database was used for Tsc22d3 gene regulatory kinase analysis. The TargetScanHuman 7.2, MiRDB, and ENCORI databases were used to execute the analysis of the Tsc22d3 gene regulatory miRNAs. Then, the GSCALite and GEPIA2021 databases were used to investigate the correlation between Tsc22d3 expression and immune infiltration. Results: The expression of the Tsc22d3 gene was upregulated markedly in AML cells relative to normal hematopoietic stem cells. The expression of the Tsc22d3 gene was increased in AML tumor samples compared with healthy bone marrow samples. And overexpression of the Tsc22d3 gene was associated with poor OS in AML patients.This study implied that the Tsc22d3 gene is a new biomarker for predicting the prognosis of AML. Furthermore, gene ontology analysis showed that Tsc22d3 was involved in leukemia. Functional enrichment analysis showed that the Tsc22d3 gene has many biological functions, including the regulation of many genes, kinases, miRNAs, signaling pathways, and immune infiltration.Therefore, this study suggests that the Tsc22d3 gene may be a potential therapeutic target for AML. Conclusions: Tsc22d3 gene expression was upregulated in AML, and overexpression was associated with poor OS in AML patients. Therefore, the Tsc22d3 gene may serve as a novel prognostic biomarker and therapeutic target for AML.

The effect of non-invasively obtained central blood pressure on cardiovascular outcome in diabetic patients in Assiut University Hospitals

Background The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by the presence of hypertension. Therefore, proper control of BP in diabetic hypertensive patients is essential. Few studies have specifically investigated the prognostic significance of central BP in Egyptian populations with diabetes and hypertension and its relation with cardiovascular outcome. This study aims to evaluate relation between central BP and diabetic composite cardiovascular complications. Results Diabetic patients with CVD were significantly older (p value < 0.01), obese (p value < 0.01) with long duration of diabetes (p value < 0.001) and had significantly higher peripheral and central systolic and diastolic BP and higher AIx@75(p values < 0.01) than those without CVD. Regarding the metabolic parameters, they had significantly higher fasting blood glucose, HbA1c, and higher blood cholesterol levels (p values < 0.001), higher LDL (p value < 0.01), triglycerides levels (p value = 0.014), and microalbuminuria (p value = 0.028). Logistic regression analysis found increased BMI, central systolic BP, and AIx@75 were independent predictors of composite CVD (p values < 0.05). Conclusions There is a pattern of favorability towards central rather than peripheral BP indices to predict the occurrence of CVD in diabetic patients.

Overexpression of SKA Complex Is Associated With Poor Prognosis in Gliomas

The spindle and kinetochore-associated complex is composed of three members: SKA1, SKA2, and SKA3. It is necessary for stabilizing spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis. The SKA complex is associated with poor prognosis in several human cancers. However, the role of SKA complex in rare malignant diseases, such as gliomas, has not been fully investigated. We investigated several databases, including Oncomine, UALCAN, and cBioPortal to explore the expression profile and prognostic significance of SKA complex in patients with gliomas. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathways were used to analyze the potential enriched pathways. The genes co-expressed with SKA complex were identified and used for developing a protein-protein interaction (PPI) network using the STRING database. We found a significant overexpression of the mRNA levels of SKA1, SKA2, and SKA3 in patients with glioma patients. Higher expression of SKA1 and SKA3, but not SKA2, was significantly correlated with shorter overall survival of patients with glioma. In glioma, SKA complex was found to be involved in nuclear division, chromosome segregation, and DNA replication. The results of PPI network identified 10 hub genes (CCNB2, UBE2C, BUB1B, TPX2, CCNA2, CCNB1, MELK, TOP2A, PBK, and KIF11), all of which were overexpressed and negatively associated with prognosis of patients with glioma. In conclusion, our study sheds new insights into the biological role and prognostic significance of SKA complex in glioma.

Clinicopathological Characteristics and Prognostic Factors in Axial Chondroblastomas: A Retrospective Analysis of 61 Cases and Comparison with Extra-Axial Chondroblastomas

Background The clinical characteristics and prognostic factors of axial chondroblastoma (ACB) are still poorly understood. Purpose To characterize clinicopathological characteristics in a large ACB cohort and investigate their correlation with survival. We also sought to compare these results with extra-axial CB (EACB). Methods Our institution's local database was retrospectively reviewed and included a total of 132 CB patients, including 61 ACB patients and 71 EACB patients. Immunohistochemistry was used to assess the expression levels of Vimentin (Vim), S100, and cytokeratin (CK) on tumor cells in 132 tissue specimens. Results Overall, ACB and EACB had similar characteristics, except for older age and tumor size, as well as higher Vim expression, incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction. Whereas wide resection and absence of invasion of surrounding tissues were consistently associated with favorable survival in the ACB and EACB cohorts in univariate analysis, most parameters showed differential prognostic significance between the 2 groups. Significant prognostic factors for local recurrence-free survival in multivariate analysis included the type of resection and chicken-wire calcification in the ACB cohort. Multivariate analysis of overall survival demonstrated that the type of resection was a significant predictor in the ACB cohort, whereas the type of resection and postoperative sensory or motor dysfunction were predictive of overall survival in the EACB group. Conclusion These data suggest that there may be distinct biological behaviors between ACB and EACB and may provide useful information to better understand the prognostic characteristics of patients with ACB and to improve outcome prediction in patients with ACB.

Nutritional Risk Index Predicts Survival in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy

Nutritional risk index (NRI) is an index based on ideal body weight that aims to present body weight and serum albumin levels. It has been utilized to discriminate patients at risk of postoperative complications and predict the postoperative outcome of major surgeries. However, this index remains limited for breast cancer patients treated with neoadjuvant chemotherapy (NACT). The research explores the clinical and prognostic significance of NRI in breast cancer patients. This study included 785 breast cancer patients (477 cases received NACT and 308 cases did not) were enrolled in this retrospective study. The optimal NRI cutoff value was evaluated by receiver operating characteristic (ROC) curve, then reclassified as low NRI group (&lt;112) and high NRI group (≥112). The results demonstrated that NRI independently predicted survival on disease-free survival (DFS) and overall survival (OS) by univariate and multivariate Cox regression survival analyses [P = 0.019, hazard ratio (HR): 1.521, 95% CI: 1.071–2.161 and P = 0.004, HR: 1.415, 95% CI: 1.119–1.789; and P = 0.026, HR:1.500, 95% CI: 1.051–2.143 and P &lt; 0.001, HR: 1.547, 95% CI: 1.221–1.959]. According to the optimal cutoff value of NRI, the high NRI value patients had longer mean DFS and OS time in contrast to those with low NRI value patients (63.47 vs. 40.50 months; 71.50 vs. 56.39 months). Furthermore, the results demonstrated that the high NRI score patients had significantly longer mean DFS and OS time than those with low NRI score patients in early-stage breast cancer (χ2 = 9.0510, P = 0.0026 and χ2 = 9.2140, P = 0.0024) and advanced breast cancer (χ2 = 6.2500, P = 0.0124 and χ2 = 5.8880, P = 0.0152). The mean DFS and OS values in patients with high NRI scores were significantly longer in contrast to those with low NRI scores in different molecular subtypes. The common toxicities after NACT were hematologic and gastrointestinal reactions, and the NRI had no statistically significant effects on toxicities, except in nausea (χ2 = 9.2413, P = 0.0024), mouth ulcers (χ2 = 4.8133, P = 0.0282), anemia (χ2 = 8.5441, P = 0.0140), and leukopenia (χ2 = 11.0951, P = 0.0039). NRI serves as a minimally invasive, easily accessible and convenient prognostic tool for evaluating breast cancer prognoses and treatment efficacy, and may help doctors in terms of selecting measures of greater efficiency or appropriateness to better treat breast cancer.