ABSTRACT
Background: The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms. Methods: This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test. Results: Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = -0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001). Conclusions: The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.
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Introduction: Hypoxia fuels cancer growth by supporting blood vessel formation, suppressing immune response, and helping cancer cells adapt to harsh surroundings. This happens when cancer cells react to low oxygen levels by activating hypoxia inducible factor-1 alpha (HIF-1α). High levels of HIF-1α can indicate an aggressive form of cancer and resistance to treatment in diffuse large B-cell lymphoma (DLBCL) patients. This study aimed to identify which factors are linked to HIF-1α distribution using immunohistochemistry in DLBCL patients. Method: This study conducted at a hospital in Indonesia between 2020 and 2022 aimed to investigate factors associated with HIF-1α expression in DLBCL patients. Newly diagnosed DLBCL patients were categorized into two groups based on HIF-1α distribution (<40% and ≥40%). Various factors were analyzed between the two groups using statistical tests such as χ2, Mann-Whitney U, and Spearman correlation tests. Results: In this study, 40 participants diagnosed with DLBCL were divided into two groups based on their HIF-1α distribution. The group with HIF-1α distribution greater than or equal to 40% had a higher incidence of extranodal involvement, including primary extranodal disease, compared to the group with less than 40% distribution. This difference was statistically significant. The authors also found that haemoglobin level statistically significant (P=0.041) in this research. The Spearman test analysis showed negative correlation between haemoglobin (P = <0.05, r = -0.44) and positive correlation of soluble interleukin-2 receptor (sIL-2R) (P = <0.05, r = 0.5) with vascular endothelial growth factor (VEGF), as well as between tumour volume (P = <0.05, r = 0.37) with sIL-2R. Additionally, there was a positive correlation between VEGF and sIL-2R (P = <0.05, r= 0.5). Conclusion: Patients with higher HIF-1α expression (≥40%) had more extranodal involvement and primary extranodal disease in this study of 40 DLBCL patients. Haemoglobin level, sIL-2R, and VEGF were also identified as potential biomarkers.
ABSTRACT
While the association of hypoxia has been established in various types of solid cancers, little is known about its presence and existence in diffuse large B-cell lymphoma (DLBCL). The purpose of the present study was to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in DLBCL and to analyze the association of these factors with several clinical and pathological characteristics. The immunohistochemical protein expression of HIF-1α and VEGF-A was investigated in 34 de novo DLBCL tumor samples from January 2017 to December 2017 from the Department of Hematology/Medical Oncology and Anatomical Pathology at Dr Kariadi Hospital (Semarang, Indonesia). The present study revealed by using immunohistochemistry (IHC), that hypoxic markers were overexpressed (88.2% for both HIF-1α and VEGF-A) in the vast majority of patients with DLBCL. Only in 4 tumors, was HIF-1α expression normal, and interestingly VEGF-A was negative as well. There was a significant correlation in the intensity of staining of HIF-1α and VEGF-A using our custom scoring system in surgically resected tissues (r=0.475; P=0.005). Both HIF-1α and VEGF-A were also associated to serum LDH and tumor diameter. Collectively, HIF-1α and VEGF-A were predominantly expressed in the majority of DLBCL tumor cells. The findings of the present study indicate the existence of hypoxia in DLBCL tumors similar to numerous solid cancers, and thus warrants further investigation to clarify its role as a potential pathogenic or prognostic marker in this type of hematological cancer.
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OBJECTIVE: This study aims to determine the role of beetroot extract in overcoming the chemoresistance of Neoadjuvant Adriamycin Cyclophosphamide (NAC) regimens with a target immune response in the tumour microenvironment at the pre-clinical stage. METHODS: This study was conducted on rats with 7,12-Dimethyl Benz (α) Anthracene (DMBA) induced mammary adenocarcinoma. Adriamycin Cyclophosphamide was given in 4 cycles, whereas beetroot extract was administered three times each cycle. Observations of CD8 T cells and Myeloid Derivative Suppressive Cells (MDSC) expression levels and pathological responses were carried out on tumour tissue taken at the end of the observation. RESULTS: Supplementation of beetroot extract to NAC could significantly increase CD8 T cells and decrease MDSC in the tumour microenvironment. The addition of beetroot extract gave a better pathological response. CONCLUSION: Beetroot extract enhances the immune response in the tumor microenvironment so that it has the potential to overcome chemoresistance in NAC.
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Subject(s)
Adenocarcinoma , Breast Neoplasms , Animals , Breast Neoplasms/pathology , Cyclophosphamide/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Female , Humans , Immunity , Neoadjuvant Therapy , Plant Extracts/pharmacology , Rats , Tumor MicroenvironmentABSTRACT
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in Asia and Indonesia. DLBCL could be further classified according to cell of origin as the germinal center B-cell (GCB) subtype or the non-germinal center B-cell (non-GCB) subtypes; of these, the non-GCB subtype usually has poorer prognosis. The purpose of this study is to determine the relationship between the cell-origin subtype and 3-year overall survival of patients with DLBCL at Kariadi General Hospital Semarang. METHODS: This research represents an observational analytical study of 36 patients with DLBCL who visited Kariadi General Hospital between January and August 2017. Data on age of diagnosis, tumor location, disease stage, and 3-year overall survival were collected. DLBCL subtype was determined via immunohistochemical examination of CD10, BCL6, and MUM1 protein expression. Data analyses, including the chi squared test and Kaplan-Meier curves, were conducted. RESULTS: The study population included 18 patients with GCB-subtype DLBCL and 18 patients with non-GCB-subtype DLBCL. No significant difference (P = 0.171) between disease stage and cell-origin subtype was noted between groups. Patients with the non-GCB subtype had a 3-year overall survival that was significantly worse than that of patients with the GCB subtype (P = 0.026). Moreover, the 3-year survival rate of patients with the non-GCB subtype of the disease was 38.9% while that of patients with the GCB subtype was 77.8%. Patients with advanced stages of DLBCL also had a 3-year overall survival that was significantly worse than those of patients with early stages of the disease (P < 0.001), with the 3-year survival rate of patients with advanced stage was 14.3%. CONCLUSION: Patients with non-GCB-subtype DLBCL or advanced stages of the disease have a lower 3-year overall survival rate and poorer prognosis compared with those with other subtypes or earlier stages of the disease.