Analysis of natural resistance-associated macrophage protein-1 (NRAMP-1) level based on death, comorbidities and severity of COVID-19 patients: a cross-sectional study.

An accurate diagnosis of COVID-19 is essential for pandemic control and for establishing adequate therapeutic strategies to reduce morbidity and mortality. COVID-19 infection replicates in macrophage cells and affects the immune system. Natural resistance-associated macrophage protein-1 (NRAMP-1) carries cation ions, such as Fe2+, Zn2+ and Mn2+, and plays an essential role in the immune system to infection with micro-organisms. In addition, the function of NRAMP-1 is to limit the replication of pathogens by changing the phagosomal environment. Levels of NRAMP-1 protein are based on death, comorbidities and clinical symptoms of COVID-19 patients and it is possible for the soluble protein NRAMP-1 level to be used as an additional biomarker for forensic and medicolegal related COVID-19 cases and prosecutions from patients and families. Methods: Determination of NRAMP-1 protein levels using the enzyme link-immunosorbent assay technique in death, had comorbidities and severity of clinical symptoms of COVID-19 patients. Results: Of the 62 patients who received treatment, 10 patients died with an average NRAMP-1 level of 650 ng/ml and 52 patients who survive with an average NRAMP-1 level of 1065.26 ng/ml. The results of the study also found that 34 patients had comorbidities with an average NRAMP-1 level of 838.82 ng/ml and 28 patients without comorbidities with an average NRAMP-1 level of 1191.92 ng/ml. Based on the severity of clinical symptoms in survive patients, 10 patients with mild were found with an average NRAMP-1 level of 984.31 ng/ml, with moderate in 31 patients with an average NRAMP-1 level of 1104.71 ng/ml and severe in 11 patients with an average NRAMP-1 level of 1027.71 ng/ml. Conclusions: NRAMP-1 protein levels were significantly lower in COVID-19 patients who died and had comorbidities.

CD8+ TILS Expression in Invasive Breast Carcinoma (No Special Type).

Invasive breast carcinoma (IBC) is the most cancer in women (24%) and the cause of cancer death in women worldwide. Based on data from globocan 2018 shows the incidence of breast cancer is around 2.08 million (11.6%) which is the second rank of all cancers after lung cancer with a mortality rate of 626.6 thousand (6.6%) which is also the most common cause of death in women. The basic role of the immune system in maintaining homeostasis by immunosurveillance and initiation of the inflammatory reactions that include coordination of innate and adaptive immune cells activation against tumor cells is one of the most important in the mechanism of tumor cell elimination. Prognosis of IBC were influenced by several factors, including tumor histology grade and Tumor Infiltrating Lymphocytes (TILs). Infiltration of lymphocytes in the tumor microenvironment/TILs through CD8+ T lymphocytes is known to be an important component of adaptive immunity that eliminates tumor cells. CD8+ T cells present tumor antigens on the surface of the major histocompatibility complex class I (MHC class I). Based on its importance in clinical application and it's role in biological concepts, this study was conducted to determine the expression of CD8+ in Invasive Breast Carcinoma of No Special Type (IBC-NST) grades 1,2 and 3. Analytical study with a cross-sectional design on IBC-NST samples from 2017 until 2020 at the Laboratory of Anatomic Pathology, Faculty of Medicine, Hasanuddin University Makassar from May to August 2021. Immunoexpression data were analyzed to determine its relationship with grade. Eighty samples met the inclusion and exclusion criteria, there were 17 samples (21.3%) with grade 1, 32 samples (40%) with grade 2, and 31 samples (38.8%) with grade 3. In the high CD8+ TILs group, from a total of 27 samples, 10 samples with grade 1, 6 samples with grade 2, and as many as 11 samples with grade 3. In the low CD8+ TILs group, from a total of 53 samples, there were 7 samples with grade 1, 26 samples with grade 2, and 20 samples with grade 3. Based on the Chi-square test, p value = 0.017 (p <0.05). There is a significant difference in CD8+ TILS in Invasive Breast Carcinoma of No Special Type grade 1, grade 2 and grade 3.

Association of chemokine (CXC motif) receptor 4 expression with lymphovascular invasion and lymph node metastasis of invasive breast cancer.

BACKGROUND: The histological tumor grade influences the prognosis of breast cancer. In metastatic breast cancer, stromal cells produce chemokine (CXC motif) ligand 12 or stromal cell-derived factor-1 as a chemoattractant, which binds to chemokine (CXC motif) receptor 4 (CXCR4) expressed by breast cancer cells. OBJECTIVE: This study aimed to determine the expression of CXCR4 in invasive breast cancer in relation to lymphovascular invasion (LVI) and lymph node metastasis. METHODS: This observational study retrospectively investigated a paraffin block archived sample diagnosed with invasive breast cancer. The results of immunohistochemical staining with CXCR4 antibody and expression analysis were evaluated using light microscopy. The data were statistically analyzed using the chi-square test and presented in a table using SPSS version 18. P-values of <0.05 were considered statistically significant. RESULTS: The expression of CXCR4 was significantly associated with the incidence of LVI and lymph node metastasis in invasive breast cancer (both p = 0.001). CONCLUSIONS: The results show that the expression of CXCR4 varies and support its decisive role in the incidence of LVI and lymph node metastasis in invasive breast cancer.

CD133 Act as an Essential Marker in Ovarian Carcinogenesis.

OBJECTIVE: To analyze the role of cancer stem cells (CSC) in ovarian carcinogenesis through the identification of CD133 expression in the normal ovary (NO), serous cystadenoma (SC), borderline serous tumour (BST), low-grade serous carcinoma (LGSC), and high-grade serous carcinoma (HGSC). MATERIALS AND METHODS: A total of 48 tissue samples contain 5 NO, 10 SC, 5 BST, 8 LGSC, and 20 HGSC were stained with anti-CD133 antibody by immunohistochemical protocol. The difference in the H-score of CD133 expression between groups and their relationship to age, histomorphology, and localization was analyzed. RESULTS: CD133 expression varied among tumor groups, with clinicopathologic parameters showing diverse associations (age p = 0.773; histomorphology p = 0.001; and localization p = 0.026). The comparison of CD133 H-scores differed significantly between each group (p = 0.0031), in which precursor and malignant lesions possessed more robust CD133 expression. CONCLUSION: The presence of CD133 cellular expression and localization in different types of serous ovarian tumours suggests that these markers are involved in ovarian tumorigenesis.

Gata-3 and KI-67 expression in correlation with molecular subtypes of breast cancer.

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis.

Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in colorectal adenocarcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are considered have a prognostic value in several malignancies. This study investigated the correlation between PD-L1 expression of tumor cells with the degree of stromal TILs in colorectal adenocarcinoma. METHODS: A cross sectional study design performed by taking 52 colorectal adenocarcinoma samples. The specimens were stained by immunohistochemical procedure using PD-L1 rabbit monoclonal antibody and the degrees of TILs were assessed base on hematoxylin and eosin (H&E) staining. RESULTS: From a total of 52 samples, the positive PD-L1 expression of tumor cells were 44 (84.6%) samples with 22 (50.0%), 18 (40.9%) and 4 (9.1%) samples had low-, moderate-, and high-degree TILs, respectively. While the negative PD-L1 expression were eight (15.4%) samples with 1 (12.5%), three (37.5%) and four (50.0%) samples had low-, moderate-, and high-degree TILs, respectively. A value of P=0.017 (P<0.05) was obtained by the Chi-square test. CONCLUSIONS: This study concluded that there was a significant correlation between PD-L1 expression of tumor cells and the degree of TILs in colorectal adenocarcinoma. This result indicated that the degree of TILs had the potential to be used as a predictive factor for PD-L1 expression of tumor cells in colorectal adenocarcinoma.