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.

Single or Daily Application of Topical Curcumin Prevents Ultraviolet B-Induced Apoptosis in Mice.

Curcumin is a natural ingredient with antioxidant effects, widely studied as a treatment for various types of cancer. However, its effects on ultraviolet radiation have not been fully explored. The effects of single or daily application of 0.1-100 µM curcumin on cell apoptosis in ultraviolet B (UVB)-induced mice were tested using an experimental double-blind posttest design with a control group and two research models: a single application of curcumin before a single UVB exposure and daily application of curcumin for 7 days before a single UVB exposure on the seventh day. Apoptotic cells were counted using a tunnel system kit. The number of apoptotic cells under a single or daily application of curcumin for 7 days was significantly lower than that of the UVB controls (p ≤ 0.05). The number of apoptotic cells decreased with the increasing concentration of curcumin, and the maximum effect was observed at 100 µM. Daily application of topical curcumin was superior in preventing apoptosis (mean apoptotic cell count of 14.86 ± 1.68) compared with a single application (17.46 ± 0.60; p = 0.011). Topical curcumin can act as a potential photoprotective agent in preventing cutaneous malignancies due to UVB radiation. Further studies are warranted, especially in humans.

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.

Significance of Histone H3.3 (G34W)-Mutant Protein in Pathological Diagnosis of Giant Cell Tumor of Bone.

OBJECTIVE: This study aimed to examine the expression of Histone H3.3 glycine 34 to tryptophan (G34W) mutant protein in Giant Cell Tumor of Bone (GCTB). METHODS: This analytic observation research used a cross-sectional study design on 71 bone tumors. The cases involved 54 tissue samples diagnosed as GCBT. It was divided into GCTB primer (n=37), recurrent GCTB (n=5), GCTB with metastasis (n=9), and malignant GCTB (n=3). There were 17 samples mimics of GCTB also tested, including chondroblastoma (n=1), giant cell reparative granuloma (n=2), giant cell of tendon sheath (n=7), chondromyxoid fibroma (n=2), aneurysmal bone cyst (n=2), and giant cell-rich osteosarcoma (n=3). The Immunohistochemistry was used to evaluate the expression of G34W-mutated protein in these bone tumors. RESULT: The representation H3.3 (G34W) was expressed in the nuclei of mononuclear stromal cells but not stained on osteoclast-like giant cells. This study was analyzed by the Chi-square test, Fisher's test, specificity test, and sensitivity test. We obtained p = 0.001 for Histone H3.3 (G34W) mutant expression in GCTB vs Non-GCTB. Statistically, there was no significant difference in the expression level of Histone H3.3 (G34W) in the GCTB and its variants p-value = 0.183. We also obtained that the specificity of Histone H3.3 expression on GCTB was 100% and the sensitivity of Histone H3.3 on GCTB was 77.8%. CONCLUSION: Histon H3.3 mutant as a mutated driver gene in an Indonesian GCTB can assist to diagnose GCTB and compare it from other bone tumors.

Diagnostic Accuracy of Lymph Nodes Fine Needle Aspiration Biopsy Based on The Sydney System for Reporting Lymph Node Cytology.

OBJECTIVE: To evaluate the diagnostic accuracy and malignancy risk of The Sydney System Reporting for Lymph Nodes Cytology. MATERIAL AND METHODS: This study utilized secondary data from 156 cases to conduct a retrospective analysis of a diagnostic test method. During 2019-2021, data were collected at Dr. Wahidin Sudirohusodo's Anatomical Pathology Laboratory in Makassar, Indonesia. The cytology slides of each case were split into five diagnostic groups using the Sydney method, which were then compared with the results of the histopathological diagnosis. RESULTS: There were six cases in the L1 category, thirty-two cases in the L2 category, thirteen patients in the L3 category, seventeen cases in the L4 category, and ninety-one cases in the L5 class. The malignant probability (MP) is computed for each diagnostic classification. L1 MP value is 66.7%, L2 MP value is 15.6%, L3 MP value is 76.9%, L4 MP value is 94.0%, and L5 MP value is 98.9%. The diagnostic value of the FNAB examination is as follows: 89.9% sensitivity, 92.9% specificity, 98.2% positive predictive value, 68.4% negative predictive value, and 90.47% diagnostic accuracy. CONCLUSION: The FNAB examination provides high sensitivity, specificity, and accuracy in diagnosing lymph node tumors. Using a classification based on the Sydney system promotes communication between laboratories and clinicians.
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The Relationship Between Expression of EpCAM Cancer Stem Cell Marker with Histopathological Grading, Lymphovascular Invasion, and Metastases in Colorectal Adenocarcinoma.

OBJECTIVE: The aim of this study was to analyze the expression of EpCAM in the colorectal adenocarcinoma. MATERIAL AND METHODS: This study used a cross-sectional design. One hundred and thirteen paraffin embedded block of Colorectal Adenocarcinoma were assessed using anti-EpCAM/Epithelial Specific Antigen (Ber-EP4) mouse monoclonal antibody and their expression were performed using Olympus CX-43 light microscope. The relationship between EpCAM expression with histopathological grade of colorectal adenocarcinoma, lymphovascular invasion and metastases ability were statistically analyzed by Chi-Square tests and presented in tables using SPSS 18. RESULTS: From 113 samples, in samples with lymphovascular invasion there were 37 samples (32.7%) with strong expression, while those with weak expression were 19 samples (16.8%). There were 39 samples with metastases and strong expression of EpCAM (34.5%), while 21 samples with weak expression (18.6%). There was a significant relationship between the expression of cancer stem cell marker EpCAM with lymphovascular invasion and colorectal adenocarcinoma metastases (p = 0.002), but there was no significant relationship with histopathological grade (p = 0.574). CONCLUSION: The EpCAM expression can be used as a prognostic factor, and can be considered as a predictive or an option for target therapy in colorectal adenocarcinoma.

Association of high expression of CD44 in clinicopathological factors of endometrial cancer.

BACKGROUND: Clinical stages, histologic type, degree of cell differentiation, myometrial invasion, and lymph-vascular space invasion (LVSI) have been identified as clinicopathological factors that are predictive for endometrial cancer, however, further prognostic indicators are still required to account for the heterogeneity of this cancer. Adhesion molecule CD44, affects the invasion, metastasis, and prognosis of many forms of cancer. The purpose of this study is to examine the expression of CD44 in endometrial cancer and its correlation with established prognostic variables. METHODS: A cross-sectional study was conducted on 64 samples of endometrial cancer from Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital. Immunohistochemical analysis was used to detect CD44 expression using mouse anti-human CD44 monoclonal antibody. Differences in Histoscore were studied to determine the association between CD44 expression and clinicopathological factors of endometrial cancer. RESULTS: Of the overall sample, 46 samples were in the early stage, whereas 18 samples were in the advanced stage. High expression of CD44 was associated with advanced stage compare than early stage (P=0.010), poor differentiation compare than well-moderate differentiation (P=0.001), myometrial invasion ≥50% compare than myometrial invasion <50% (P=0.004), and positive LVSI compare than negative LVSI (P=0.043) in endometrial cancer, but not associated with histological type of endometrial cancer (P=0.178). CONCLUSIONS: High expression of CD44 may be considered as a poor prognostic marker and predictive marker for targeted therapy in endometrial cancer.

The role of xenobotic metabolism MGST1 gene polymorphism in colorectal cancer patients.

AIM: to asses the role of Microsomal Glutathione S-Transferase1 (MGST1) gene as one of enzym metabolism that plays in enviromental factor. METHODS: using case-control study, subjects with age less than 50 years were collected from teaching hospital Makassar between 2008-2010. Frozen or routinely processed tumour samples biopsy and peripheral blood were obtained from 35 CRC patients undergoing surgery and endoscopic examination with 61 subject as control. CRC cases were diagnosis by clinical examination and confirm by histopathology without familial aggregation of CRC. DNA resequencing was conducted for the 3 kb genomic DNA region MGST1 using PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: from 96 subject, two varian single nucleotide polymorphisms (SNPs) 16454T>G and 16416G>A MGST1 were identified. Significant CRC association (p= 0.047) was detected in GG genotipe SNP 16454T>G MGST1 with 3.5 fold risk (95% confidence interval (CI) 0.962-13.191). CONCLUSION: the results suggest that MGST1 gene polymorphisms as one of environment gene may contribute to CRC risk in younger age (<50 years old).

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.

Expression of CD133 Cancer Stem Cell Marker in IDH-Mutant and IDH-wildtype (Isocitrate Dehydrogenase) Astrocytoma.

OBJECTIVE: This study evaluated the differences between IDH1-R132H and CD133 expression in different categories of  astrocytoma. MATERIAL AND METHODS: This study used a cross-sectional design.  Sixty-seven paraffin embedded block of Diffuse Astrocytoma (DA), Anaplastic Astrocytoma (AA) and Glioblastoma (GB) were assessed using using the monoclonal antibody IDH1-R132H and Rabbit polyclonal antibody CD133. RESULTS: It was found that there was a significant relationship between the expression of IDH1-R132H and CD133 in DA, AA and GB (p<0.001). Astrocytoma with IDH-mutant molecular status will express more markers of cancer stem cell CD133 than IDH-wildtype. CONCLUSION: The IDH1-R132H and CD133 can provide predictive value on treatment success, disease prognosis, recurrence and can be considered as target combination therapy with chemotherapy.

Topical Curcumin as Chemoprotector Against Photoproducts Production: The Role of Cyclobutyl Pyrimidine Dimers, 8-Hydroxy2'Deoxyguanosine Expression and Epidermal Hyperplasia in Acute and Chronic UVB-Induced Mice.

Background: Ultraviolet B (UVB) exposure leads to formation of photoproducts leading to cellular damage. Prevention using sunscreen can sometimes be inadequate and can be an economic burden. Recent studies have suggested the photoprotective effect of curcumin. Objective: To examine the acute and chronic photoprotective effect of topical curcumin, using cyclobutyl pyrimidine dimers (CPD) and 8-hydroxy2'deoxyguanosine (8-OHdG) expression as markers of DNA-induced damage, and epidermal hyperplasia on UVB-induced mice. Methods: Three treatment groups were established. Group A (negative control) consisted of 5 mice, Group B and C were further divided into two categories to assess acute and chronic effects of topical curcumin and UVB radiation. Each consisted of six subgroups of five mice. Subgroup 1; UVB exposure only (positive control) subgroup 2; acetone and UVB exposure, subgroup 3-6; topical curcumin application of 100nM, 1µM, 10µM, and 100µM concentrations, respectively. In Group C, there were two categories that received 3x/week UVB exposure for three weeks which effects were being observed at 24 hours and 10 days after the last exposure. The topical curcumin dose was 2mg/mL/cm2 applied 30 minutes prior to 343mJ/cm2/day UVB irradiation. Skin biopsy was done one hour after the last UVB exposure for immunohistochemical and histopathology examinations. Results: Topical curcumin showed a limited yet robust protective effect against CPD and 8-OHdG expression in Group B, while in Group C all concentrations showed significant CPD and 8-OHdG inhibition after 10 days of UVB exposure. The 10µM and 100µM concentrations showed the best epidermal hyperplasia inhibition effect (p<0.05). No significant differences were found in terms in efficacy either in single nor daily application. Conclusion: Topical curcumin can prevent the formation of the photoproducts CPD and 8-OHdG and epidermal hyperplasia in both acute and chronic exposure in UVB-induced mice.

The Role of Claudin-1 Expression in Follicular and Papillary Thyroid Neoplasm.

OBJECTIVE: This study evaluated differences in Claudin-1 expression between follicular adenoma (FA), follicular thyroid carcinoma (FTC), follicular variant papillary thyroid carcinoma (FV-PTC), and papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: This study used a cross-sectional approach. Immunostaining using the polyclonal antibody Claudin-1 was performed on 75 samples divided into 20 samples for follicular adenoma, follicular thyroid carcinoma, papillary carcinoma, and 15 samples of follicular variant thyroid carcinoma, respectively. RESULTS: Claudin-1 expression is detected on the cytoplasmic membrane of tumor cells and appears to be varied among thyroid neoplasms. The claudin-1 expression score revealed a statistically significant difference between FA against FV-PTC, FA versus (vs) PTC, and FTC vs PTC, with median values of 4 vs 6 (p = 0.016), 4 vs 8 (p = 0.001), and 5 vs 8 (p = 0.002), respectively. However, there was no statistically significant difference in scores between the FA and the FTC (4 vs 5), or between the FTC and the FV-PTC groups (5 vs 6 (p=1,000). CONCLUSION: These results suggest that Claudin-1 may be capable of discriminating follicular adenoma from classic and follicular variant of papillary thyroid carcinoma. It can also differentiate follicular thyroid carcinoma and papillary thyroid carcinoma, especially for cases challenging to assess by hematoxylin and eosin staining. It still holds promise in providing targeted cancer therapy.

Effect of retinol and α-tocopherol supplementation on photoreceptor and retinal ganglion cell apoptosis in diabetic rats model.

BACKGROUND: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. Retinol and α-tocopherol of diabetic models prevent the damage of photoreceptor and retinal ganglion cells (RGC) caused by hyperglycemia. OBJECTIVE: This study aims to examine the effect of retinol and α-tocopherol on photoreceptor and RGC densities and the expression of caspase-3 and -7 on the retinal layers of the diabetic rat model. METHODS: Alloxan 150 mg/kg body weight single dose was used to develop animal models, which were separated into eight groups. These consist of one group without intervention (group 1), one positive control with only induced alloxan (group 2), and others receiving retinol (group 3 and 6), α-tocopherol (group 4 and 7), or their combination (group 5 and 8). Furthermore, histopathological examination was performed using Hematoxylin-Eosin staining to evaluate the photoreceptor and RGC densities, while immunohistochemistry staining evaluated the caspase-3 and -7 expressions. RESULTS: In the treatment group, the highest and lowest densities were identified in diabetic rats given α-tocopherol (group 7) and retinol (group 3) respectively. The caspase-3 and -7 expression showed that the group given α-tocopherol (group 7) had the lowest value. CONCLUSION: In diabetic rats, retinol and α-tocopherol compounds maintained densities and prevented photoreceptor and RGC death. However, α-tocopherol was more promising than retinol or combinations in the prevention of retinal cells apoptosis.

Relation between expression of hMLH1 and p53 mRNA genes, in the feces of patients with colorectal carcinoma. Cross-sectional study.

Colorectal carcinoma (CRC) is one of the main public health problems. The mortality of CRC is about 8%. Early detection of CRC is very important to prevent death because this cancer could be cured through surgery if the diagnosis can be made as early as possible. Therefore screening strategy for early detection of CRC is critical in reducing mortality. Many investigations supporting the detection of CRC have been developed, including the fecal DNA mutation test using advanced cytological techniques. It is capable of assessing colonocytes for the presence of DNA, RNA, and protein as molecular biomarkers of neoplasia in CRC, including p53 and hMLH1. This study implemented observational approach with a cross-sectional study of the feces of patients with CRC regardless of the stage and grade. The purpose of this study was to determine the expression of the hMLH1 and p53 mRNA genes in the feces of 48 patients with CRC from two hospitals in Indonesia, Siloam Hospitals in Cikarang and Dr. Wahidin Sudirohusodo Hospital in Makassar. The results showed that all adenocarcinoma feces samples with various tumor stages and grades had excess mRNA expression (more than twice the normal amount in Fold Change units) for both the hMLH1 and p53 genes. The average expression of the hMLH1 mRNA gene was the highest at stage two and grade one, while the lowest was at stage four and grade three. In contrast, the average p53 mRNA gene expression was the highest at stage four and grade three, while the lowest was at stage two and grade one. The study suggested that there was a relation between and the expression of hMLH1 and p53 mRNA gene. We concluded that while both hMLH1 and p53 genes in patients' feces with CRC were overexpressed, they did not significantly affect the grade of CRC.

Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis.

Background: Diagnosis and management of latent tuberculosis (TB) infections are one of the challenges of eradicating pulmonary TB. A critical aspect of controlling pulmonary TB spread is early diagnosis. One TB biological marker type under evaluation is microRNAs (miRNAs). Mycobacterium tuberculosis infection causes epigenetic changes. The upregulation of miRNA-29a-3p suppresses the immune response by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells, increasing susceptibility to pulmonary TB. This study aimed to assess miRNA-29a-3p expression as a biomarker of active and latent pulmonary TB infection. Methods: This case-control study included 50 individuals with active TB, 33 household contacts with a positive IFN-γ release assay (IGRA), and 30 healthy controls. An enzyme-linked immunosorbent assay-based IGRA was used to determine latent pulmonary TB infection in household contacts. Quantitative real-time PCR was used to quantify miRNA-29a-3p expression. Data analysis used analyses of variance and receiver operating characteristic (ROC) curves. Results: miRNA-29a-3p expression differed significantly between active TB, latent TB, and healthy participants (controls; p = <0.001. ROC curve analysis showed that miRNA-29a-3p expression had 86% sensitivity and 73% specificity with an area under the ROC curve (AUC) of 0.763 (95% confidence interval [CI]: 0.668-0.858). The miRNA-29a-3p ROC curve had 84.8% sensitivity and 70% specificity with an AUC of 0.808 (95% CI: 0.698-0.919) for latent TB. Additionally, miRNA-29a-3p expression was significantly correlated with active (p < 0.0001) and latent (p < 0.0001) pulmonary TB. However, miRNA-29a-3p expression was not significantly correlated with INF-γ levels in patients with active (R = 0.005; p = 0.62) and latent (R = 0.010; p = 0.38) pulmonary TB or healthy controls (R = 0.060; p = 0.19). Conclusion: miRNA-29a-3p expression was increased in patients with active and latent pulmonary TB. Therefore, miRNA-29a-3p represents a potential biomarker for latent and active pulmonary TB. However, IFN-γ levels were not correlated with miR-29a-3p expression.

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.

Family with Peutz-Jeghers syndrome in Indonesia.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterised by mucocutaneous pigmentation, gastrointestinal polyps and an increased risk of gastrointestinal and other cancers. We report an Indonesian woman, aged 28, with black spots on her lips who had multiple polyps extending from the stomach to the rectum. Her father and a son also had mucocutaneous lesions but they did not undergo gastrointestinal investigations. All three had mutations in the serine/threonine kinase 11 gene (STK11).

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 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.

Genetic risk factors for colorectal cancer in multiethnic Indonesians.

Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.