CD133, CD47, and PD-L1 Expression in Ovarian High-grade Serous Carcinoma and Its Association with Metastatic Disease: A Cross-sectional Study.

INTRODUCTION: Ovarian cancer is a primary cause of cancer-related death in women. At the time of diagnosis, the majority of ovarian malignancies had metastasized. It is believed that cancer stem cells (CSCs) and immune evasion play a crucial role in the metastatic process. The objective of this study was to describe the expression profiles of cluster of differentiation (CD)133, CD47, and programmed death ligand 1 (PD-L1) in high-grade serous ovarian cancer (HGSC) as commonly utilized markers for CSCs and immune evasion. MATERIAL AND METHODS: Using an immunohistochemical procedure, 51 HGSC tissue samples were stained with anti-CD133, anti-CD47, and anti-PDL1 antibodies. The samples contained 31 HGSC with metastases and 20 HGSC absent metastases. The expression of CD133, CD47, and PD-L1 was compared between groups. RESULTS: Strong expression of CD133 and CD47 was seen in 52% and 66% of tissue samples, respectively. Twenty of the thirty-one patients with metastases had a significant level of CD133 expression, with a p-value of 0.039. CD47 expression was increased in 26 of 31 samples with metastatic disease. A 62.7 percent of samples were negative for PD-L1 expression, significantly inversely correlated with HGSC metastatic disease (p=0.023). Although there was no significant association between CD133, CD47, or PD-L1 expression and age, Tumor Infiltrating Lymphocytes demonstrated a significantly varied relationship. CONCLUSION: Our findings suggested that expression of CD133, CD47, and PD-L1 may have dynamically increased as the primary lesion progressed to the metastatic lesion, implying that these proteins may be involved in the progression of high-grade serous ovarian cancer from the primary to the metastatic stage.

Risk-stratification machine learning model using demographic factors, gynaecological symptoms and ß-catenin for endometrial hyperplasia and carcinoma: a cross-sectional study.

BACKGROUND: Demographic features, suggestive gynaecological symptoms, and immunohistochemical expression of endometrial ß-catenin have a prognostic capacity for endometrial hyperplasia and carcinoma. This study assessed the interaction of all variables and developed risk stratification for endometrial hyperplasia and carcinoma. METHODS: This cross-sectional study was conducted from January 2023 to July 2023 at two teaching hospitals in Makassar Indonesia. Patients (< 70 years old) with suggestive symptoms of endometrial hyperplasia or carcinoma or being referred with disease code N.85 who underwent curettage and/or surgery for pathology assessment except those receiving radiotherapy, or chemotherapy, presence of another carcinoma, coagulation disorder, and history of anti-inflammatory drug use and unreadable samples. Demographic, and clinical symptoms were collected from medical records. Immunohistochemistry staining using mouse-monoclonal antibodies determined the ß-catenin expression (percentage, intensity, and H-score) in endometrial tissues. Ordinal and Binary Logistic regression identified the potential predictors to be included in neural networks and decision tree models of histopathological grading according to the World Health Organization/WHO grading classification. RESULTS: Abdominal enlargement was associated with worse pathological grading (adjusted odds ratio/aOR 6.7 95% CI 1.8-24.8). Increasing age (aOR 1.1 95% CI 1.03-1.2) and uterus bleeding (aOR 5.3 95% CI 1.3-21.6) were associated with carcinoma but not with %ß-catenin and H-Score. However, adjusted by vaginal bleeding and body mass index, lower %ß-catenin (aOR 1.03 95% 1.01-1.05) was associated with non-atypical hyperplasia, as well as H-Score (aOR 1.01 95% CI 1.01-1.02). Neural networks and Decision tree risk stratification showed a sensitivity of 80-94.8% and a specificity of 40.6-60% in differentiating non-atypical from atypical and carcinoma. A cutoff of 55% ß-catenin area and H-Score of 110, along with other predictors could distinguish non-atypical samples from atypical and carcinoma. CONCLUSION: Risk stratification based on demographics, clinical symptoms, and ß-catenin possesses a good performance in differentiating non-atypical hyperplasia with later stages.

The Association of "First 1000 Days of Life" Training Program on Communication Skill and Empathy of Undergraduate Medical Students: A Cross-Sectional Study.

Introduction: 1000 First Days of Life (1000FDL) training program is carried out for 2 years from the 3rd to 6th semester; in this program, students are asked to accompany pregnant women until their children are 2 years old. This study aimed to analyse undergraduate medical students' communication skills and empathy levels and determine the association between communication skills and empathy after the training program. Methods: This is a cross-sectional study in which 176 undergraduate medical students in Hasanuddin University participated; they were enrolled in 1000FDL training program and selected using purposive sampling. Data were collected using Modified Arabic Version of the ABIM's Patient Assessment (MAV-ABIM) and Jefferson Scale of Empathy - Student Version (JSE-S) questionnaires to assess their level of communication skills and empathy. In this study, demographic data were obtained using a semi-open-ended questionnaire. Data were analysed using descriptive statistics, Chi-Square, and Spearman tests. Results: Communication skill was very good (83.5%), good (15.9%), and inadequate (0.6%), while the empathy level was high (9.1%), medium (25%), and low (65.9%). There was no significant difference between the level of communication skills (p-value 0.168) and empathy (p=0.145) based on gender, but there was a significant difference between <12 or >12 times interaction with the empathy level (p<0.001). The association between the level of communication showed that the level of empathy was significant (p<0.001, r=0.399). Conclusion: Undergraduate medical students had very good communication skills but low empathy levels. There was a positive association between communication skills and empathy level after the training program. The students' empathy level can be improved by increasing the frequency of interaction with patients in experiential learning through training programs.

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.

Primary leiomyosarcoma of the breast: A case report and literature review.

INTRODUCTION: Primary leiomyosarcoma is an uncommon form of stromal breast sarcoma. Approximately 73 cases have been documented in English-language literature to date. To our knowledge, this is the first report from Indonesia of an adolescent female with primary leiomyosarcoma of the breast. CASE PRESENTATION: A 30-year-old Southeast Asian female presented with a tumor in her left breast. Clinical examination revealed a 12 × 8-centimeter tumor. The supraclavicular, subclavicular, and axillary lymphadenopathy were not palpable. An ultrasound revealed a Breast Imaging Reporting and Data System category 5. Abdominal ultrasonography and chest x-ray were normal, as were blood chemistry and routine blood tests. A wide excision with a surgical margin of 2 cm was performed. Pathological investigation identified the mass as a leiomyosarcoma. The pelvis, abdomen, and lung CT scan metastatic workups were negative. The patient is well 8 months post-surgery, with no signs of recurrence. CLINICAL DISCUSSION: Wide local excision has been the mainstay of treatment for leiomyosarcoma; however, there is no accepted standard of treatment due to the rarity of the disease. CONCLUSION: Breast leiomyosarcomas have a more favorable prognosis than other breast neoplasms; however, patients must be closely monitored for recurrence or metastases. While there are no known predictors of outcomes, the margins of the initial surgery, mitotic activity, and atypia cellularity are more indicative of malignancy.

Prognostic Value of ß-Catenin and L1CAM Expressions in Type I Endometrial Carcinoma.

OBJECTIVE: The aim of this study is to evaluate the expression of ß-catenin and L1CAM in the type I of Endometrial Carcinoma. MATERIAL AND METHODS: This study was an analytical study with a cross-sectional design using 49 samples of type I Endometrial Carcinoma. Immunohistochemical method was used to evaluate the expression of ß-catenin and L1CAM related to two significant prognostic parameters i.e., lymphovascular space invasion (LVSI) and metastases event of type I Endometrial Carcinoma samples. RESULTS: From all samples collected, based on the presence of LVSI, there were 17 cases (34.7%) with LVSI and 32 (65.3%) no LVSI. Among them, there were 13 cases that included lymph node or omental samples in type I Endometrial Carcinoma, 5 (38.5%) cases of metastasis, and 8 (61.5%) cases that did not metastasize. The statistical results showed that there was a significant correlation between ß-catenin and L1CAM expressions examined from tumor cells with lymphovascular space invasion and the presence of metastases in the type I Endometrial Carcinoma (p <0.05). CONCLUSION: This study suggest that the positive expression of ß-catenin together with L1CAM can participate in the development of tumor cells in type I Endometrial Carcinoma, in its ability to involve lymphovascular space invasion, and metastases to other sites. Our results indicate that both of ß-catenin and L1CAM are prominent biomarkers for the prognosis of type I Endometrial Carcinoma.

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.

Vascular endothelial growth factor-A expression is significantly correlated with HER2 expression in late-stage breast cancer patients.

BACKGROUND: Molecular marker analysis has become important in breast cancer diagnosis and treatment and may reveal new mechanisms in breast cancer pathogenesis. Aside from the commonly used hormonal receptors and HER2, VEGF-A has been increasingly shown to be important in breast cancer diagnosis and pathogenesis. OBJECTIVE: This study aimed to determine the relationship between VEGF-A expression on ER and PR and HER2 hormonal status in patients with late-stage breast cancer (locally advanced or with distant metastases). METHODS: This observational, cross-sectional study examined VEGF-A expression and molecule markers (ER, PR, and HER2) of breast cancer tissue using immunohistochemistry. The Chi-square test was used to determine whether two categorical variables were correlated. Statistical significance was set at p < 0.05. RESULTS: VEGF-A showed no significant correlation with demographic characteristics, TNM staging, pathological grading, luminal or non-luminal type, or hormonal receptor markers but showed a significant positive correlation with HER2 receptors (p = 0.036). CONCLUSIONS: VEGF-A was positively correlated with HER2 expression in breast tumor tissue but showed no significant correlation with other breast cancer markers, including luminal typing or hormonal receptors. Further study is needed to understand the mechanistic interplay between VEGF and HER2 in breast cancer pathogenesis.

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.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type.

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients' samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient's management.

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.

The expression of programmed death-ligand 1 and its association with histopathological grade, stage of disease, and occurrence of metastasis in breast cancer.

INTRODUCTION: Programmed death ligand 1 (PD-L1) plays a role in tumor escape and progression by inactivating T lymphocytes. The aim of the study reported here was to determine the relationship between the expression of PD-L1 and histopathological grade, stage of disease, and the occurrence of metastasis in breast cancer. METHODS: The observational cross-sectional study involved analyzing the expression of PD-L1 by immunohistochemistry. RESULTS: PD-LI was expressed in 43 of 60 patients with breast cancer (71.6%), mostly with a moderate histopathological grade (58.3%) and at an advanced stage (50%). Associations between the expression of PD-L1 and histopathological grade (p = 0.011), stage of disease (p = 0.009), and the occurrence of metastasis (p = 0.01) were significant, with an odds ratio of 5. CONCLUSION: The associations between the expression of PD-L1 and histopathological grade, disease stage, and occurrence of metastasis were all significant in cases of breast cancer in the sample. Those findings suggest that the expression of PD-L1 increases the progression of breast cancer.

Association of ERα-36 expression with the de novo resistance of tamoxifen in ER-positive breast cancer.

BACKGROUND: Approximately 70-80% of breast cancer express ER-alpha and hormonal therapies, given significant improvements in patient survival. About 50% of ER-positive breast cancer patients with advanced disease insensitive to tamoxifen treatment when diagnosed. Recent studies have shown that ERα-36 is a crucial factor in the resistance of tamoxifen. OBJECTIVE: This study aims to determine the association between ERα-36 expression and de novo resistance of tamoxifen in patients with ER-positive breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and Unhas Hospital. ERα-36 protein expression was assessed using an immunohistochemistry assay. The association of ERα-36 expression and resistance of tamoxifen was tested with the Chi-square test. RESULTS: A total of 50 locally advanced breast cancer cases were included in this study, 22 cases (44%) had overexpression of ERα-36, and 28 cases (56%) had not, 24 cases (48%) had experience resistance to tamoxifen and 26 cases (52%) had not. There was a significant association between ERα-36 expressions and resistance of tamoxifen (p = 0.000). CONCLUSIONS: There was an association between the expression of ER-α36 with de novo resistance of tamoxifen in ER-positive breast cancer. ER-α36 could act as a worth considering biomarker for de novo resistance of tamoxifen in therapeutic strategies.

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.

Ki-67 Expression by Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction as Predictor of Clinical Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

BACKGROUND: Chemotherapy has become a standard of treatment in managing breast cancer. To achieve proper treatment for the right patients, the predictive marker is needed. Ki-67 is a biomarker of proliferation for solid tumor. Studies mentioned association of Ki-67 expression with chemotherapy response. The study aims are to evaluate whether Ki-67 expression detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) may predict clinical response to neoadjuvant chemotherapy in breast cancer. METHODS: This study utilized a longitudinal study. IHC and qRT-PCR methods were used for detection of Ki-67 expression. Chemotherapy response was calculated using RECIST. Data were analyzed with Chi-square and Wilcoxon's test. RESULTS: There were 48 subjects in this study. Analysis of Ki-67 expression with chemotherapy response has a significant correlation with p = 0.025 (<0.05), OR: 1.69, confidence interval (95% CI) 1.022-2.810. Analysis of Ki-67 mRNA expression with chemotherapy response has a significant correlation p = 0.002 (<0.05), OR: 6.85, confidence interval (95% CI) 1.064-44.193. Detection of Ki-67 expression using IHC and qRT-PCR has similar results, p = 0.012 (<0.05). CONCLUSION: These results suggest that Ki-67 expression detected by both IHC and qRT-PCR is considered to be a predictor of clinical response to neoadjuvant chemotherapy in locally advanced breast cancer.