Prognostic Value of Vimentin in Triple Negative Breast Cancer Patients Depends on Chemotherapy Regimen and p53 Mutant Expression.

Purpose: To determine the prognostic value of vimentin in triple negative breast cancer (TNBC) patients, specifically in relation to chemotherapy regimen and p53 mutant expression. Patient and Methods: We retrospectively analyzed the association of pre-treatment tumor expression of vimentin with 48-month overall survival (OS) of 72 all stages TNBC patients diagnosed between 2014 and 2018 in relation to chemotherapy regimen and expression of p53 mutant. Vimentin and p53 mutant expressions were examined using immunohistochemistry. Analysis was conducted on all patients collectively, then repeated on two cohorts divided according to the chemotherapy regimen. Sub-analysis was performed to determine the effect of p53 mutant expression on the prognostic value of vimentin. Results: Vimentin was expressed in 43.1% of patients and was not associated with clinicopathologic characteristics. Vimentin was associated with improved 48-month OS in all patients in univariate analysis but not significant in multivariate analysis. When analyzed according to chemotherapy regimen, vimentin was independently associated with improved 48-month OS in patients receiving non-platinum-based chemotherapy (80% vs 15.8%; HR: 0.17, 95% CI: 0.05-0.58, p: 0.005). Other independent prognostic factors include T (HR: 6.18, 95% CI: 1.38-27.7, p: 0.017) and M (HR: 5.64, 95% CI: 1.2-26.33, p: 0.028). On subanalysis, vimentin was significantly associated with improved 48-month OS in patients expressing p53 mutant (69.2% vs 22.2%, p: 0.006) but was not significant in patients not expressing p53 mutant. Conclusion: Vimentin expression was independently associated with improved 48-month OS in TNBC patients treated with non-platinum-based chemotherapy. Expression of p53 mutant significantly affected the prognostic value of vimentin.

Breast cancer incidence in Yogyakarta, Indonesia from 2008-2019: A cross-sectional study using trend analysis and geographical information system.

BACKGROUND: Breast cancer is a significant public health concern worldwide, including in Indonesia. Little is known about the spatial and temporal patterns of breast cancer incidence in Indonesia. This study aimed to analyze temporal and spatial variations of breast cancer incidence in Yogyakarta Province, Indonesia. METHODS: The study used breast cancer case data from the Yogyakarta Population-Based Cancer Registry (PBCR) from 2008 to 2019. The catchment areas of the PBCR included the 48 subdistricts of 3 districts (Sleman, Yogyakarta City, and Bantul). Age-standardized incidence rates (ASR) were calculated for each subdistrict. Joinpoint regression was used to detect any significant changes in trends over time. Global Moran's and Local Indicators of Spatial Association (LISA) analyses were performed to identify any spatial clusters or outliers. RESULTS: The subdistricts had a median ASR of 41.9, with a range of 15.3-70.4. The majority of cases were diagnosed at a late stage, with Yogyakarta City having the highest proportion of diagnoses at stage 4. The study observed a significant increasing trend in breast cancer incidence over the study period the fastest of which is in Yogyakarta City with an average annual percentage change of 18.77%, with Sleman having an 18.21% and Bantul having 8.94% average changes each year (p <0.05). We also found a significant positive spatial autocorrelation of breast cancer incidence rates in the province (I = 0.581, p <0.001). LISA analysis identified 11 subdistricts which were high-high clusters in the central area of Yogyakarta City and six low-low clusters in the southeast region of the catchment area in the Bantul and Sleman Districts. No spatial outliers were identified. CONCLUSIONS: We found significant spatial clustering of BC ASR in the Yogyakarta Province, and there was a trend of increasing ASR across the region. These findings can inform resource allocation for public health efforts to high-risk areas and develop targeted prevention and early detection strategies. Further res is needed to understand the factors driving the observed temporal and spatial patterns of breast cancer incidence in Yogyakarta Province, Indonesia.

Sexual Dysfunction Following Breast Cancer Chemotherapy: A Cross-Sectional Study in Yogyakarta, Indonesia.

Introduction Sexual dysfunction is rarely studied in Indonesian patients with breast cancer. We aimed to assess the prevalence of sexual dysfunction symptoms following chemotherapy, as well as the pattern and the associated factors. Methods This cross-sectional study included 135 female breast cancer patients receiving primary chemotherapy. The present study measured the prevalence of sexual dysfunction symptoms using an e-questionnaire containing Common Toxicity Criteria for Adverse Events (CTCAE) version 4 at different time points. Other data included sociodemography, clinicopathology, treatment, and other concurrent symptom characteristics. Bivariate and multivariate logistic regression tests were used to analyze any association among variables. Results In the whole panel, 86 (63.7%) of 135 cases experienced sexual dysfunction. The most common symptom was vaginal dryness (45.9%), followed by decreased libido (45.2%), dyspareunia (13.3%), delayed orgasm (11.1%), and anorgasmia (8.9%). When observed at five different time points, the frequency of symptoms increased during chemotherapy and persisted until six months after completing treatment. Chemotherapy duration of >120 days was associated with a higher probability of vaginal dryness (p=0.012) and decreased libido (p=0.033). Spouse age ≥55 years old and body mass index (BMI) ≥23 kg/m2 were associated with a reduced probability of decreased libido (p=0.033 and 0.025, respectively). The presence of comorbidity was associated with a reduced probability of delayed orgasm (p=0.034). Conclusions A significant proportion of patients with breast cancer had sexual dysfunction following chemotherapy. Vaginal dryness, decreased libido, and dyspareunia were the commonest symptoms observed. Duration of chemotherapy, spouse age, BMI, and comorbidity were associated with the risk of sexual dysfunction occurrence.

Malaria as Potential Aetiology and Treatment Complicating Factor in DLBCL Patient: A Case Report.

Malaria is known to be a significant risk factor and also a potential complicating factor during the treatment of lymphoid malignancy. There has not been a reported case of malaria reactivation that occurred weeks after cytotoxic chemotherapy completion, especially in non-endemic regions. Our patient was a 47-year-old man with a history of repeated falciparum malaria infection experiencing 2 months of progressive unilateral nasal blockage and recurrent anterior epistaxis, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) through pathological examination. He was treated with six cycles of classical R-CHOP, resulting in complete remission. One month after remission, he experienced shivering, fever, sweating, and a return to normal temperature, which repeated irregularly for roughly 1 week. His laboratory result showed anaemia, leucopenia, and profound thrombocytopenia. Immunochromatographic testing (ICT) confirmed the diagnosis of falciparum malaria. This case was considered a relapse since our centre is not in the malaria-endemic region. He was cured with a combination of dihydroartemisinin-piperaquine and primaquine. Our case demonstrated the duality of malaria as potential aetiology and treatment complicating factor in DLBCL.

The occurrence and risk factors of chemotherapy-induced neutropenia in patients with breast cancer not receiving primary G-CSF prophylaxis.

Background: Chemotherapy-induced neutropenia (CIN) is a substantial side effect in chemotherapy of breast cancer patients. Administration of granulocyte colony stimulating factor (G-CSF) that may reduce CIN occurrence is not commonly available to many local cases. Objectives: To investigate the occurrence of grade 4 CIN and the influencing factors in breast cancer patients not receiving G-CSF prophylaxis. Methods: One-hundred and eighty-six newly diagnosed breast cancer patients who received a 3-weekly (neo)adjuvant or palliative chemotherapy without primary G-CSF prophylaxis were included. Grade 4 CIN was defined as absolute neutrophil count (ANC) <0.5 × 103/mm3 during any chemotherapy cycle. We used logistic regression to explore the association of clinical, pathological and treatment factors with the risk of grade 4 CIN in the first cycle and in any given cycle. Results: Fifty-seven (30.6%) patients experienced grade 4 CIN in the first cycle and 145 (78%) had it at least once during chemotherapy. In the first cycle, haemoglobin, ANC, and albumin levels were associated with grade 4 CIN (OR = 1.48, p = 0.031; OR = 0.68, p = 0.006; and OR = 2.07, p = 0.042). In any cycle, pre-treatment ANC levels and anthracycline-taxane combination regimen were associated with grade 4 CIN (OR = 0.78, p = 0.032 and OR = 3.64, p = 0.012). Conclusions: A significant proportion of the local breast cancer cases undergoing chemotherapy without primary G-CSF prophylaxis experienced grade 4 CIN. Haemoglobin, ANC, and albumin levels are the risk factors for first cycle CIN, while pre-treatment ANC levels and anthracycline-taxane chemotherapy regimen are associated with CIN in any given cycle. These risk factors may be used to direct a recommendation of G-CSF prophylaxis to the most at-risk individuals in the local setting or other settings in similar situations.

Regulatory T Cells but Not Tumour-Infiltrating Lymphocytes Correlate with Tumour Invasion Depth in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common skin malignancy worldwide. Current evidence suggests tumour-infiltrating lymphocytes (TILs) may influence the clinical outcomes of patients with BCC. The present study aimed to profile the infiltrative characteristics of stromal TILs and regulatory T cells (Treg cells) in the tumour centre (TC), tumour periphery (TP), and normal adjacent tissue (NAT) of BCC. A total of 111 samples from 43 cutaneous BCC cases were examined for TIL (CD3+) and Treg cell (FOXP3+/CD3+) expression using immunohistochemical techniques. The correlations of Treg cells with TILs, invasion depth, and tumour morphological risk were analysed. We identified a high mean proportion of Treg cells within the tumour (TC = 46.9%, TP = 56.1%, NAT = 51.8%) despite a relatively low median of TILs (TC = 12.7%, TP = 10.3%, NAT = 3.6%), supporting the classification of BCC as a cold tumour. A significant positive correlation was observed between the proportion of Treg cells and sTILs (ρ = 0.325, p < 0.001), suggesting a predominant role of TILs in the infiltration of Treg cells. An inverse correlation discovered between Treg cells and tumour invasion depth (r = −0.36, p = 0.017) might indicate Treg cells' anti-tumour capacity in BCC.

The Association between Abdominal Obesity, Metabolic Syndrome and Survival Outcomes in Patients with Breast Cancer.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been linked to the risk of developing certain cancers. This study aimed to analyze the association between obesity markers, MetS and survival outcomes of patients with breast cancer. METHODS: This study retrospectively investigated patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-), nonmetastatic breast cancer diagnosed between January 2010 and December 2019. Data on clinical conditions, body mass index (BMI), waist-to-hip ratio (WHR), MetS, time of metastasis and death were collected. RESULTS: A total of 223 breast cancer patient records were eligible for analysis. Obesity (BMI ≥ 25) was found in 38.1% of cases. Abdominal obesity measured as WHR ≥ 0.85 was found in 48.9%. Metabolic syndrome was detected in 56.1% of patients and was associated with older age (OR = 2.196, p = 0.005), postmenopausal status (OR = 2.585, p = 0.001), obesity (OR = 5.684, p = 0.001) and abdominal obesity (OR = 2.612, p = 0.001). Obesity was not associated with poor disease-free survival (DFS) or overall survival (OS), while abdominal obesity was modestly associated with poor DFS (HR = 1.539, p = 0.083) and OS (HR = 3.117; p = 0.019). Multivariate analysis revealed that WHR ≥ 0.85 was independently associated with unfavorable DFS (HR = 1.907, p = 0.027). Patients with MetS had a similar survival rate to those with normal metabolism. CONCLUSION: In Indonesian women with HR+/HER2- breast cancers, obesity and MetS were not associated with poor survival outcomes. The abdominal obesity marker (WHR) was more accurate in predicting unfavorable DFS.

Stromal Tumor Infiltrating Lymphocytes (sTILs) Were Associated with a Higher Grade and a Lower Stage of Indonesian Triple Negative Breast Cancers.

OBJECTIVE: This study aimed to investigate the association of sTILs with clinicopathological parameters and overall survival (OS) in patients with triple negative breast cancer (TNBC). METHODS: One hundred and twenty-five paraffin embedded tissue of patients with TNBC, collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, between 2008-2017, were used in this study. Stromal TILs were examined from hematoxylin and eosin (H&E)-stained samples, and classified as either low or high score using 20% cut-off. Analysis of the association of sTILs with clinicopathological parameters, relative risk (RR) and OS used 95% confidence interval (CI) with significance set as p<0.05. RESULTS: The higher proportion of TNBC patients in this study were ≥40 years old (83.3%), high tumor grade (68%), tumor stage >IIIa (56%), alive (50.4%), and with low sTILs (54.4%). The results showed significant association between sTILs and a higher grade or a lower stage of tumor (B = 0.259, 95%CI = 0.090-0.468, p = 0.004 and B = -0.255, 95%CI = -0.433 - -0.080, p = 0.005, respectively ). Meanwhile sTILs were not associated with age at diagnosis (B = 0.027, 95%CI = -0.193 - 0.264  p = 0.758 nor 3-year OS of patients (HR = 0.342, 95%CI = 0.41 - 1.43  p = 0.402). CONCLUSION: The results indicate that sTILs may serve as an additional pathological parameter for TNBC.

Vitamin D status in breast cancer cases following chemotherapy: A pre and post observational study in a tertiary hospital in Yogyakarta, Indonesia.

OBJECTIVES: To observe pre- and post-treatment vitamin D level and its association with treatment and concomitant factors in breast cancer patients treated with chemotherapy. METHODS: We performed a pre-post observational analysis that nested in an ongoing prospective cohort study of breast cancer patients at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 136 subjects were recruited from the main study. Information on subjects' socio-demographic characteristics clinical status, and tumour profile was assessed at baseline. Number of chemotherapy cycles and chemotherapy-induced nausea vomiting (CINV) were also recorded. Vitamin D concentration was measured using ELISA methods at baseline and post-treatment. Vitamin D level of <20 ng/ml and <12 ng/ml were defined as deficiency and severe deficiency. Correlation between socio-demographic and clinical profile with baseline vitamin D was tested using Spearman correlation. Paired t-test was used to evaluate changes in post-treatment vitamin D concentration. The odds ratio for a subject to experience post-treatment vitamin D decrease was assessed based on number of chemotherapy cycles and CINV severity. RESULTS: The mean vitamin D level before chemotherapy was very low (8.80±3.64 ng/ml) in the whole panel. Higher AST level were associated with lower vitamin D level at baseline (r = -0.188, p = 0.028). Severe deficiency was found in 82.4% subjects at baseline and the rate increased to 89.0% after chemotherapy. Eighty-five cases showed a decrease level whereas 51 showed a slight improvement. Overall, a significant decrease of the vitamin D level was observed after chemotherapy (median change 3.13±4.03 ng/ml, p <0.001). Subjects who received >6 cycles of chemotherapy were less likely to experience a decreased level of post-treatment vitamin D (OR = 0.436, 95% CI = 0.196-0.968, p = 0.039). CONCLUSIONS: Indonesian breast cancer patients showed pre-existing severe vitamin D deficiency and deterioration of vitamin D after chemotherapy. Future research is needed to explore its implication towards patients' survival in the local setting. Evidence-based approach also needs to be taken to address this modifiable condition, including increasing awareness of the importance of maintaining vitamin D sufficiency both in patients and the general population.

The Combined Effect of Downregulated RB1 and Overexpressed lncRNA SSTRS-AS1 on Prediction Time to Castration-Resistant Prostate Cancer: Indonesian Cohort Studies.

OBJECTIVE: Identifying the mechanism underlying the initiation and development of castration-resistant prostate cancer remains challenging. Time to castration-resistant prostate cancer is defined by prostate-specific antigen progression and may represent a risk factor for developing immune alterations with a negative prognostic role in the overall survival of patients with prostate cancer. This study aimed to evaluate the combined effect of downregulated RB1 and overexpressed SSTR5-AS1 as biomarkers for predicting time to castrationresistant prostate cancer. MATERIAL AND METHODS: The clinical and pathological data of patients with prostate cancer were collected retrospectively. Between 2015 and 2019, a total of 36 patients who received castration were included. Expressions of mRNA of RB1 and SSTR5-AS1 from primary tumors were quantified using quantitative realtime polymerase chain reaction. Patients were divided into 2 groups: the first group consisted of patients with Rb1 expression lower than the median and expression of SSTRS5-AS1 higher than the median, and the second group consisted of all the other patients. This study was conducted in compliance with the latest Helsinki Declaration and registered on Elsevier International Standard Randomized Controlled trial number registry. RESULTS: In this study, patients with both downregulated RB1 and overexpressed Long non-coding RNAs (lncRNA) SSTR5-AS1 showed shorter time to castration-resistant prostate cancer (mean 23.6 ± 3.3 months) compared to other groups (mean 38.3 ± 4.9 months) (log-rank test, P=.028). CONCLUSION: The combination of downregulation of RB1 and overexpression of SSTR5-AS1 is a strong predictor of shorter time to castration-resistant prostate cancer in the Indonesian population. Additionally, patients with International Society of Urological Pathology (ISUP) score >4 did not demonstrate this predictive value on time to castration-resistant prostate cancer.

The Association of Intra-Tumoral and Stromal Vitamin D Receptor (VDR) Expressions with Molecular Subtypes and Clinicopathological Factors in Breast Carcinoma.

OBJECTIVE: This study aimed to investigate the association between intra-tumoral and stromal VDR expressions with molecular subtypes and clinicopathological factors. METHODS: A total of 75 formalin-fixed paraffin embedded tissue samples were stained using immunohistochemical methods. The VDR expressions were measured by counting brown-stained nuclei in intra-tumoral and stromal areas. The association of VDR expression with molecular subtypes and clinopathological factors was examined. Statistical analysis was performed by chi square tests. RESULTS: High intra-tumoral VDR expression was found in carcinomas with luminal molecular subtypes (p=0.039) and low histological degrees (p=0.035). High VDR expression in the stroma was found in breast carcinomas with large tumor sizes. CONCLUSIONS: High intra-tumoral VDR expression is found in breast carcinomas with luminal subtypes and low histological grade (I/II). Both factors are known to have a good prognosis. These findings further strengthen the function of VDR as anti-tumorigenesis.

Potential relative quantities of miR-122 and miR-150 to differentiate hepatocellular carcinoma from liver cirrhosis.

Cirrhosis and hepatocellular carcinoma (HCC) are related to chronic liver diseases. Diagnostic algorithms are needed to discriminate HCC from cirrhosis for better patient management. This study aimed to determine the potential of miR-122 and miR-150 to differentiate HCC from liver cirrhosis. This study used a cross-sectional method involving 66 patients with liver cirrhosis, 27 subjects with HCC, and 29 healthy controls. Examination of miR-122 and miR-150 levels from blood plasma used real-time quantitative polymerase chain reaction and their relative expressions were calculated. Clinical and laboratory data were collected and graphed for the Area Under the Curve (AUC) and also for comparison using unpaired T-tests, Kruskal-Wallis, Mann-Whitney, and Chi-square tests with significance set as p < 0.05. The relative expressions of miR-122 and miR-150 could differentiate HCC from cirrhosis, with cut-off 9.11, AUC 53.84%, p = 0.2120, and cut-off 1.47, AUC 67.65%, p = 0.0001, respectively. Meanwhile, the combined relative expressions of miR-122 and miR-150 can distinguish HCC from cirrhosis, with AUC 71.94%, p = 0.0006. The combination of miR-122 and miR-150 has the potential as a biomarker to differentiate HCC from liver cirrhosis.

Diagnostic Accuracy of Immunohistochemistry in Detecting MGMT Methylation Status in Patients with Glioma.

BACKGROUND: The O6-methylguanine-DNA methyltransferase (MGMT) gene prevents mismatch in DNA replication and transcription by repairing mutagenic DNA lesions. MGMT is a predictor biomarker of chemotherapy in high-grade and low-grade gliomas based on high-risk clinical conditions. It also can be used for therapeutic decisions to predict hypermutation in recurrence in newly diagnosed low-grade gliomas. The gold standard  examination for the methylation is Polymerase Chain Reaction (PCR). However, this technique is not widely available in Indonesia for daily practice. Thus, an uncomplicated and simpler method such as immunohistochemistry (IHC) is needed as an alternative examination. This study aimed to predict the diagnostic accuracy of immunohistochemistry (IHC) in detecting the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) in glioma. METHODS: This research was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) tissue samples of glioma patients, dating between October 2017 until March 2021. Diagnosis of glioma was established based on clinical, radiological, and histopathological findings. MGMT methylation status was investigated using the IHC and PCR techniques. Diagnostic value of IHC was analyzed, with PCR as a gold standard method. Optimum threshold to determine positivity of IHC was determined by the Area Under the Curve (AUC) on Receiver Operating Characteristics (ROC) curve and Youden index. RESULTS: Among 75 samples examined, 29 (38.7%) patients were methylated. IHC detected MGMT methylation with sensitivity of 86.2%, specificity of 63.0%, positive predictive value of 59.5%, negative predictive value of 87.9% and accuracy of 72.0%. The AUC was 0.746, indicating moderate diagnostic value. Optimum positivity threshold of the IHC examination based on Youden Index was 10%. CONCLUSION: IHC examination can be used to detect MGMT methylation status of glioma patients in limited resources setting, where PCR technique is not available.

Fatty Liver in Hormone Receptor-Positive Breast Cancer and Its Impact on Patient's Survival.

PURPOSE: Long-term estrogen inhibition may cause fatty liver disease (non-alcoholic fatty liver disease; NAFLD) among other adverse conditions such as osteoporosis, climacteric symptoms, thromboembolism, dyslipidemia, and metabolic syndrome. The prevalence of NAFLD among breast cancer patients ranges from 2.3%-45.2%. This study aimed to determine the risk factors for newly developed NAFLD among breast cancer patients after hormonal treatment and whether it influences survival outcomes. METHODS: This retrospective study investigated hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-), nonmetastatic breast cancer patients diagnosed between January 2010 and December 2018. All patients received adjuvant hormonal treatment for at least 6 months. Clinical data on metabolic profile indicators such as body mass index (BMI), waist circumference, serum cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), diabetes, and presence of metabolic syndrome (MetS) were collected. In total, 160 eligible patients with complete covariate data and survival follow-up were included. RESULTS: NAFLD was diagnosed in 35% of patients. There were significant associations of being overweight (BMI ≥ 25 kg/m²), waist circumference > 80 cm, triglycerides ≥ 150 mg/dL, HDL-C ≤ 50 mg/dL, LDL-C < 150 mg/dL, and presence of MetS with the development of NAFLD. However, unlike other factors, MetS and HDL-C were not independently associated with NAFLD. Patients with breast cancer who developed NAFLD had longer disease-free survival (DFS). The median DFS was not reached in the NAFLD group, whereas it was 59.3 (45.6-73.0) months in the non-NAFLD group. No worsening of overall survival was observed in patients with breast cancer and NAFLD. CONCLUSION: The development of NAFLD during treatment in patients with HR+/HER2- breast cancer was associated with several independent risk factors: being overweight, waist circumference, triglycerides, and LDL-C. Interestingly, breast cancer patients with NAFLD during treatment had longer DFS than those without NAFLD.

MicroRNA-223 is Associated with Resistance Towards Platinum-based Chemotherapy and Worse Prognosis in Indonesian Triple-negative Breast Cancer Patients.

PURPOSE: Determining the optimal strategy to implement systemic treatment modalities has been challenging in triple-negative breast cancer (TNBC). We aim to investigate the role of microRNA-223 (miR-223) as prognostic factor and predictor of response toward chemotherapy in TNBC. PATIENTS AND METHODS: We retrospectively analyzed the association of pretreatment miR-223 expression with clinicopathologic characteristics and 36-month overall survival (OS) of 53 all stages TNBC patients. Tumor level of miR-223 was measured using real-time quantitative polymerase chain reaction (expressed in fold change). Cutoff value for miR-223 was determined by using receiver operating curve (ROC). Kaplan-Meier curve was used to perform survival analysis. RESULTS: The optimum cutoff value for miR-223 was 23.435 (AUC: 0.706, 95%CI: 0.565-0.848; p:0.01; sensitivity: 78.6%; specificity: 56%) and was used to categorize mir-223 expression into over- and underexpressed group. Overexpression of miR-223 was associated with increased expression of EGFR (69.7% vs 35%, p: 0.022) and lower 36-month OS (33.3% vs 70%; median OS±SE (months): 25.66±1.58 vs 30.23±1.99; log rank p<0.05). Worse survival is observed in miR-223 overexpressed group receiving platinum-based chemotherapy compared to miR-223 underexpressed group (mean OS (95%CI) months: 24.7 (20.3-29.1) vs 34.3 (31.2-37.4); p<0.01), while no significant difference observed in non-platinum containing regimen. No significant association was observed between miR-223 expression with other clinicopathologic characteristics. CONCLUSION: Overexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.

Down-regulation of RB1 and TP53 as potential predicting biomarkers for castration-resistant prostate cancer (CRPC): Indonesian retrospective cohort study.

INTRODUCTION: Androgen deprivation therapy (ADT) has remained the first line strategy for treatment of advanced prostate cancers. Despite the profound efficacy of ADT in preventing clinical remission, 30-50% of advanced prostate cancer will develop resistance to hormonal deprivation therapy. This study aimed to evaluate the potential role of RB1 and TP53 expressions as biomarkers for predicting time to castration-resistant prostate cancer (CRPC). METHODS: The clinical and pathological data of patients with prostate cancer were collected retrospectively from Dr. Sardjito General Hospital, Yogyakarta. Between 2015 and 2019, a total of 36 patients who received castration were included. Expressions of mRNA of RB1 and TP53 from primary tumors were quantified using quantitative Real Time Polymerase Chain Reaction (qRT-PCR). RESULTS: The expressions of mRNA of RB1 and TP53 increased in prostate cancer tissues compared to hyperplastic prostates and significantly downregulated in metastatic prostate cancers (p < 0.001). Lower mRNA TP53 expression correlated with shorter time to CRPC among patients treated with ADT (p = 0.006). In addition, stratified analysis showed that lower mRNA RB1 expression was significantly associated with shorter CRPC both in metastatic (p = 0.017) and non-metastatic (p = 0.001) prostate cancer patients. CONCLUSIONS: Low expression of mRNA of RB1 and TP53 has been shown to be a potential marker of shorter time to develop CRPC in patients with advanced stages of prostate cancer treated with ADT. Meanwhile, ISUP score >4 were not shown predictive value on time to CRPC.

Overexpression of Programmed Death-Ligand 1 Receptor mRNA as an Independent Negative Prognostic Factor for Triple Negative Breast Cancer.

BACKGROUND: Triple negative breast cancer (TNBC) (represents roughly 25% of all breast cancers in Yogyakarta) still has the worst survival compared to other breast cancer subtypes. Results from recent studies have shown that inhibition of programmed death-ligand 1 receptor (PD-L1) in TNBC patients is associated with better prognosis. Currently, data on PD-L1 expression and its prognostic value in Indonesian TNBC patients are still relatively unknown. This study aimed to investigate the expression of PD-L1 in Indonesian TNBC patients as preliminary proof to support PD-L1 inhibitor as a possible treatment option near in the future. METHODS: We retrospectively included stage I-III TNBC patients diagnosed between 2014 and 2017 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Clinical variables were collected from medical record. Paraffin blocks of biopsy specimen were retrieved to examine mRNA level of PD-L1. RESULTS: We included 48 subjects with mean age of 51.09 years and mean body mass index (BMI) of 24.58. The 3-year overall survival (OS) was 58.3%. Overexpression of PD-L1 mRNA in TNBC patients is associated with worse prognosis (P < 0.01). There were no statistically significant associations between PD-L1 mRNA expression and any of the clinicopathologic variables examined. CONCLUSIONS: In summary, PD-L1 mRNA overexpression is associated with worse survival in Indonesian TNBC patients, independent of other established risk factors. PD-L1 mRNA is expressed in all of our samples, presenting as a feasible alternative or complementary method in deciding which patient might benefit from receiving PD-L1 inhibitor.

Advanced lesions of synchronous bilateral mammary Paget's disease: a case report.

BACKGROUND: Mammary Paget's disease is an eczematous eruption on the nipple and areola with underlying breast malignancy. It is often misinterpreted as chronic dermatitis or psoriasis causing a delayed diagnosis. Synchronous bilateral mammary Paget's disease is exceptionally rare and an advanced case with underlying invasive carcinoma might require long-term treatment and follow-up that could affect a patient's physical, psychological, and social aspects of well-being. CASE PRESENTATION: A 54-year-old Javanese woman presented in our clinic with a 2-year history of itching and chronic eczema in both areolae. Bilateral nipple retraction and retro-areolar palpable lumps were observed during the first presentation. Breast ultrasound revealed hypoechoic lesions in her left and right breasts. Mammograms showed an irregular hyperdense lesion and multiple microcalcifications. Histopathology from biopsy and bilateral mastectomy demonstrated infiltration of large Paget's cells in the epidermis of the areola with underlying lesions of invasive ductal carcinoma, diagnosed solid type with high nuclear grade and negative expression of estrogen receptor and progesterone receptor, with positive expression of human epidermal growth receptor-2(HER2) and Ki-67 (45%). CONCLUSIONS: In a patient with suspicious chronic inflammation of the nipple and areolae, prompt biopsy should be performed to avoid a delayed diagnosis of any malignant breast lesion.

Acquired Human Papilloma Virus Type 6-Associated Epidermodysplasia Verruciformis in a Patient With Systemic Lupus Erythematosus.

Although historically known as a genetic disorder, epidermodysplasia verruciformis (EV) might be acquired in patients with a noninherited defective cell-mediated immunity. This article reports a case of EV in a patient with systemic lupus erythematosus and a history of 3 years immunosuppressive methylprednisolone treatment. The microscopic features of the skin biopsy showed morphologic changes of the keratinocytes characteristic of human papilloma virus (HPV) infections and immunoreactivity to p16. HPV genotyping demonstrated the presence of HPV 6 which belongs to a low-risk mucosal HPV group and has not been reported in EV previously. The clinical recognition of EV in immunocompromised patients and subsequent HPV typing is important because some patients will develop squamous cell carcinoma.

Case series of cutaneous Langerhans cell histiocytosis in Indonesian children; The clinicopathological spectrum.

Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by the clonal proliferation of Langerhans cells, which are immunoreactive to S-100 and CD-1a/ CD207 (Langerin). Cutaneous involvement is the most common presentation of LCH in children. It is suggested that the patients with single-system LCH limited to the skin have a better prognosis than those with systemic involvement. Three histologic reactions of cutaneous LCH have been reported and are associated with the clinical types of LCH. These histological reactions include: proliferative, granulomatous, and xanthomatous. This study presents the clinicopathological features of ten cutaneous LCH cases collected from Dr. Sardjito General Hospital Yogyakarta Indonesia between 2014-2018. The ten cases showed various clinical features, in which some features mimic other diseases. The microscopic features of skin biopsies showed granulomatous reaction in 80% of cases and proliferative reaction in the other 20%. Five patients (50% of cases) who died had systemic manifestation of thrombocytopenia, anemia, icterus, hepatosplenomegaly, and revealed the granulomatous type from their skin biopsy specimens. The clinical recognition of LCH and subsequent histological reaction determination are important since some cases may develop multisystem disease and have a poor prognosis.