Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.

Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m2), Cyclophosphamide (600 mg/m2) with or without Taxane (75-175 mg/m2) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.

Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancer: Findings from a tertiary care institute in western part of India.

BACKGROUND: Immune checkpoint inhibitors targeting either programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have been established as a novel target for immunotherapy in non-small cell lung cancer (NSCLC). Prevalence of PD-L1 expression in NSCLC varies from 13% to 70%, with sparse data from the Indian subcontinent. In this study, we looked at PD-L1 expression and its association with demographic, clinical, radiologic and pathologic parameters in NSCLC patients. METHODS: This was an observational study carried over a period of 18 months in which 65 patients of NSCLC were included. Immunohistochemistry (IHC) for PD-L1 was done using an automated IHC stainer and testing was performed using PD-L1 IHC CAL10. For statistical analysis, unpaired t test, Chi square test, Fisher's exact test and binomial logistic regression were used. P < 0.05 was taken to be statistically significant. RESULTS: Mean age of the patients was 62.9 ± 9.2 years, and majority (87.3%) of them were males. Seventeen (26.2%) patients expressed PD-L1, among whom 10 had high PD-L1 expression (≥50%) and 7 had low PD-L1 expression (1-49%). PD-L1 expression was seen in 13 out of 43 cases of squamous cell carcinoma (SCC) and 4 out of 15 cases of adenocarcinoma. On applying binomial logistic regression analysis, association between smoking and PD-L1 expression was found to be insignificant. CONCLUSION: Almost a quarter of NSCLC cases were PD-L1 positive without any difference in expression between SCC and adenocarcinoma. PD-L1 status was not associated with any specific demographic, clinical or radiologic parameter including the histologic subtype.

Practice Patterns and Survival in Patients with Resected Pancreatic Ductal Adenocarcinomas (PDAC) - Results from the Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) Study.

BACKGROUND: There is limited data from India with regard to presentation, practice patterns and survivals in resected pancreatic ductal adenocarcinomas (PDACs). METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) included data from 8 major academic institutions across India and presents the outcomes in upfront resected PDACs from January 2015 to June 2019. RESULTS: Of 288 patients, R0 resection was achieved in 81% and adjuvant therapy was administered in 75% of patients. With a median follow-up of 42 months (95% CI: 39-45), median DFS for the entire cohort was 39 months (95% CI: 25.4-52.5), and median overall survival (OS) was 45 months (95% CI: 32.3-57.7). A separate analysis was done in which patients were divided into 3 groups: (a) those with stage I and absent PNI (SI&PNI-), (b) those with either stage II/III OR presence of PNI (SII/III/PNI+), and (c) those with stage II/III AND presence of PNI (SII/III&PNI+). The DFS was significantly lesser in patients with SII/III&PNI+ (median 25, 95% CI: 14.1-35.9 months), compared to SII/III/PNI + (median 40, 95% CI: 24-55 months) and SI&PNI- (median, not reached) (p = 0.036)). CONCLUSIONS: The MIPPAP study shows that resectable PDACs in India have survivals at par with previously published data. Adjuvant therapy was administered in 75% patients. Adjuvant radiotherapy does not seem to add to survival after R0 resection.

Gap areas in mitigation of oral cancer: A cross-sectional study evaluating awareness and knowledge of risk factors in oral cancer in a tertiary hospital.

Purpose and Objectives: One of the main causes of the increasing oral cancer (OC) burden in India is a lack of awareness and a significant gap in knowledge about risk factors and symptomology of OC. Materials and Methods: A questionnaire-based cross-sectional study was to evaluate the knowledge and awareness about OC among 500 random patients presenting for care at a tertiary hospital in western Rajasthan which serves a wide area of western, northern, and central Rajasthan. Results: A total of 446 participants, among which 83.6% were males enrolled in the study. Much to our despair, the results showed 35.23% of the participants (P = 0.007) started their habit at age <15 years. Nearly 60.3% of the participants were well aware of the harmful temporary or permanent effects of the tobacco. Around 40.85% of the participants taking tobacco products were ignorant about their changes in the tissues (site of tobacco placement). TV and Radio (50.5%) were the main source of information of the ill effects of tobacco and form a major contribution in public awareness. More than 90% of the participants had read the warnings on the tobacco packets. No doubt participants have knowledge about the ill effects of tobacco still there was a lack in behavioral modifications for tobacco cessation, leading to nonsuccess in quitting, with actual nonunderstanding about the ill effects of tobacco and overall lack of belief in the tobacco control measures. Conclusion: Our findings have found a gap in the awareness efforts of OC for the general population and will make public health professionals, clinicians, policymakers, and government a better judge and motivate them to strengthen existing national tobacco control efforts.

Deregulation of miR-10b and miR-21 Correlate with Cancer Stem Cells Expansion through the Apoptotic Pathway in Prostate Cancer.

BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate important cellular processes such as tumorigenesis, cell proliferation, and apoptosis. Cancer stem cells are a subset of cells that control metastasis and cell proliferation. In this study, we focus on the roles of miR-10b, miR-21 and correlate with cancer stem cells through the apoptotic pathway in different stages of prostate cancer (PCa). METHODS: In total, 45 patients, each group with Benign prostatic hyperplasia (BPH), localised PCa, and metastatic PCa, were recruited. MicroRNA and gene expression were estimated through quantitative polymerase chain reaction. Flow cytometry was used to characterise prostate cancer stem cells (PCSCs), estimate reactive oxygen species (ROS), apoptosis and chemiluminescent immunoassay was used to estimate interleukin 6 (IL-6), tumour necrosis factor (TNF-α), prostate-specific antigen (PSA), and testosterone. RESULTS: The fold change mean expressions of miR-21, miR-10b, Cytochrome C, and B-cell lymphoma 2 (BCL-2) were significantly upregulated in localised and metastatic PCa compared with BPH. In contrast, the mean fold change expressions of Bcl-2-associated X protein (BAX), Caspase-3, Caspase-9, and Second mitochondria-derived activator of caspase (SMAC) were lower in localised and metastatic PCa compared to BPH. The levels of IL-6, TNF-α, ROS, PSA and testosterone also showed a significant increase while apoptosis was decreased in both localized PCa and metastatic PCa as compared with BPH. In bioinformatics analyses, we found a similar pattern of miRNAs and gene expression in PCa databases. Our study also found a high expression of CD44+/CD24- and CD44+/CD133+ in localised and metastatic PCa compared with BPH. CONCLUSION: Our findings suggest miR-10b and miR-21 promote PCSCs and may target apoptotic genes involved in PCa pathogenesis; these miRNAs could be used as diagnosis biomarkers of PCa. In PCa pathogenesis and PCSCs regulation, the interaction between these two players is crucial and will help develop new PCa therapeutic targets.

Correlation of hsa miR-101-5p and hsa miR-155-3p Expression With c-Fos in Patients of Oral Submucous Fibrosis (OSMF) and Oral Squamous Cell Carcinoma (OSCC).

Aim: MicroRNAs have been widely acknowledged as a diagnostic, prognostic, and/or therapeutic biomarker for the progression of OSCC, but the correlation of hsa-miR-101-5p and hsa-miR-155-3p is yet to be established with c-Fos in OSCC and OSMF. Methodology: An observational study enrolled 40 patients divided into 2 groups: Group I-21 OSMF patients without malignant transformation, Group II-19 patients with locally advanced, large-operable, or metastatic OSCC, after applying inclusion and exclusion criteria. Both miRNAs were extracted and analyzed from the tissue sample excised from the involved site. The linear regression analysis of the expression of hsa-miR-155-3p, hsa-miR-101-5p, and levels of c-fos in OSMF and OSCC patients and its correlation for habits, age, and gender were evaluated. Results: The expression of hsa-miR-101-5p was 0.81 times downregulated in OSCC tissue compared to OSMF, whereas hsa-miR-155-3p and c-fos were both upregulated 9.30 times and 1.75 times, respectively, in OSCC tissue. In Gutkha and tobacco chewers, the hsa-miR-155-3p expression could explain 12.3% (p = 0.031) for Gutkha chewers, whereas c-fos could explain 38.6% of the cases (p = 0.020) for tobacco chewers. The expression of hsa-miR-101-5p and hsa-miR-155-3p explained 43.7% and 59.5% of OSCC cases in alcoholics, respectively. Interestingly, in non-alcoholics, hsa-miR-155-3p and hsa-miR-101-5p were significant predictors of OSCC. Conclusion: Downregulation of tumor-suppressor hsa-miR-101-5p and upregulation of proto-onco hsa-miR-155-3p is responsible for intricate regulation of the progression of OSMF to OSCC via deregulated expression of c-Fos and tobacco chewing and advancing age is significant contributors for OSCC.

In silico analysis of differentially expressed-aberrantly methylated genes in breast cancer for prognostic and therapeutic targets.

Breast cancer (BC) is the leading cause of death among women across the globe. Abnormal gene expression plays a crucial role in tumour progression, carcinogenesis and metastasis of BC. The alteration of gene expression may be through aberrant gene methylation. In the present study, differentially expressed genes which may be regulated by DNA methylation and their pathways associated with BC have been identified. Expression microarray datasets GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724 and one DNA methylation profile dataset GSE20713 were downloaded from Gene Expression Omnibus database (GEO). Differentially expressed-aberrantly methylated genes were identified using online Venn diagram tool. Based on fold change expression of differentially expressed-aberrantly methylated genes were chosen through heat map. Protein-protein interaction (PPI) network of the hub genes was constructed by Search Tool for the Retrieval of Interacting Genes (STRING). Gene expression and DNA methylation level of the hub genes were validated through UALCAN. Overall survival analysis of the hub genes was analysed through Kaplan-Meier plotter database for BC. A total of 72 upregulated-hypomethylated genes and 92 downregulated-hypermethylated genes were obtained from GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724, and GSE20713 datasets by GEO2R and Venn diagram tool. PPI network of the upregulated-hypomethylated hub genes (MRGBP, MANF, ARF3, HIST1H3D, GSK3B, HJURP, GPSM2, MATN3, KDELR2, CEP55, GSPT1, COL11A1, and COL1A1) and downregulated-hypermethylated hub genes were constructed (APOD, DMD, RBPMS, NR3C2, HOXA9, AMKY2, KCTD9, and EDN1). All the differentially expressed hub genes expression was validated in UALCAN database. 4 in 13 upregulated-hypomethylated and 5 in 8 downregulated-hypermethylated hub genes to be significantly hypomethylated or hypermethylated in BC were confirmed using UALCAN database (p < 0.05). MANF, HIST1H3D, HJURP, GSK3B, GPSM2, MATN3, KDELR2, CEP55, COL1A1, APOD, RBPMS, NR3C2, HOXA9, ANKMY2, and EDN1 were significantly (p < 0.05) associated with poor overall survival (OS). The identified aberrantly methylated-differentially expressed genes and their related pathways and function in BC can serve as novel diagnostic and prognostic biomarkers and therapeutic targets.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 4 Given name: [Jeewan Ram] Last name [Vishnoi]. Also, kindly confirm the details in the metadata are correct.It is correct.

Study of MicroRNA (miR-221-3p, miR-133a-3p, and miR-9-5p) Expressions in Oral Submucous Fibrosis and Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the common types of cancer. Its progression follows a transition from oral potentially malignant disorders (OPMDs) such as oral submucous fibrosis (OSMF). Epigenetic modifiers, especially microRNAs (miRNAs), have an appreciable role in the regulation of various carcinogenic pathways which are being used as biomarkers. miRNAs may also be helpful in the differentiation of oral submucous fibrosis from oral squamous cell carcinoma. Three miRNAs, miR-221-3p, miR133a-3p, and miR-9-5p, were found differentially expressed in many cancers in the literature search supported by our preliminary database search-based screening. The literature and our functional enrichment analysis in an earlier study have reported these miRNAs to regulate carcinogenesis at various steps. In the present study, the expression of these miRNAs was examined in 34 histopathologically confirmed OSCC, 30 OSMF, and 29 control (healthy volunteers) human samples. There was a significant downregulation of miRNA-133a-3p in OSCC compared to OSMF and controls, whereas there was up-regulation in oral submucous fibrosis compared to controls. There was no significant difference in the expression of miR-221-3p between OSCC and OSMF, but an upregulation in OSCC compared to controls. miR-9-5p was also found upregulated in both OSCC and OSMF. Further, miR-133a-3p expression was negatively correlated with age, smoking, drinking status, and AJCC staging, whereas miR-9-5p expression was only positively associated with tobacco/ areca nut chewing. The ROC plots, logistic regression model generated, and the correlation between the expression of miR-9-5p and miR-133a-3p in blood and tissue suggests that these could be used as risk stratification biomarkers.

Global and promoter specific hypermethylation of tumor suppressor genes P16, SOCS1, and SHP1 in oral squamous cell carcinoma and oral submucous fibrosis.

ABSTRACTS: Aberrant methylation pattern leads to altered gene expression, that is, involved in the transformation of various cancers, including oral squamous cell carcinoma (OSCC). In the present study, an attempt has been made to examine the association of global and promoter-specific methylation of tumor suppressor genes in patients with OSCC and oral submucous fibrosis (OSMF). Promoter-specific methylation of tumor suppressor genes P16, SOCS1, and SHP1 had been studied earlier for their aberrant methylation patterns in other cancers; however, these studies were mainly conducted in-vitro or in animal models, and as such, only a few studies are available on human samples. In the present study evaluation of promoter-specific methylation of genes P16, SOCS1, and SHP1 in 76 patients' blood and tissue samples was done and compared with methylation of 35 healthy control samples using qPCR. Further, these samples were analyzed for global methylation patterns using ELISA. The results have shown a significant decreasing trend of promoter methylation (OSCC > OSMF > Controls); the methylation indices (MI) were significantly higher in OSCC than in the controls. The median MI of three genes for OSCC were P16MI (0.96), SHP1MI (0.79), and SOCS1 (0.80). Similarly, median MIs for OSMF were P16MI (0.18), SHP1 MI (0.19), and SOCS1 MI (0.5) against controls with MI (0) for each of the three genes. The global methylation %mC values were 1.9, 0.5, and 0.1, respectively. The values of MI and %mC were found to correlate with various risk factors such as tobacco, smoking, and alcohol consumption, which are positively involved in OSMF pathogenesis followed by oral cancer progression. Further, the methylation trend in tissue was reflected in blood samples, proving a window for methylation load to be used as a lesser invasive biomarker. The sensitivity and specificity of methylation load were also found reasonable. Therefore, the current study suggests that there may be a role of global and promoter-specific methylation load in the transition of OSMF to OSCC.

Crosstalk Between Programmed Death Ligand 1, Ki-67 Labelling Index, and Tumor-Infiltrating Lymphocytes in Invasive Breast Cancer and Clinicopathological Correlations in a Tertiary Care Center in Western India.

Background & Objective: Breast cancer is the leading cancer among Indian women and accounts for about 25% of all cancer cases worldwide. The present study aimed to assess Programmed Death Ligand-1 (PD-L1) expression in tumoral cells and tumor-infiltrating lymphocytes (TILs) and evaluate their correlations with the Ki-67 labelling index in invasive breast carcinomas (IBC). Methods: This descriptive observational study was conducted during 2016-2018 and included all diagnosed cases of IBC. The relationships between PD-L1 expression, TILs, hormone receptors, Ki-67, and clinicopathological parameters were studied in IBC. Statistical analysis was performed by SPSS version 23. Results: Out of 114 evaluated cases, 33.33% (N=38) showed PD-L1+ expression in tumor cells and 47.37% (N=54) had PD-L1+ expression in TILs. A high Ki-67 index was observed in 96 cases. Moreover, 49 patients were estrogen receptor (ER)- and 65 were ER+. We observed that 22 of 49 ER- and 49 of 65 ER+ subjects showed PD-L1+ expression, respectively. Conclusion: Our results showed a significant relationship between PD-L1 expression in tumoral cells and TILs, as well as between Ki-67 and TILs. In addition, an inverse correlation was noted between PD-L1 expression and ER. The PD-L1 expression in tumors and TILs and correlation with high Ki-67 may prove the importance of PD-L1 in targeted chemotherapy. An inverse relationship between PD-L1 and ER expression in tumoral cells suggests scope for immunotherapy in ER- IBC. However, further research with more cases is required.

ABC transporters in breast cancer: their roles in multidrug resistance and beyond.

ATP-binding cassette (ABC) transporters are membrane-spanning proteins involved in cholesterol homeostasis, transport of various molecules in and out of cells and organelles, oxidative stress, immune recognition, and drug efflux. They are long implicated in the development of multidrug resistance in cancer chemotherapy. Existing clinical and molecular evidence has also linked ABC transporters with cancer pathogenesis, prognostics, and therapy. In this review, we aim to provide a comprehensive update on all ABC transporters and their roles in drug resistance in breast cancer (BC). For solid tumours such as BC, various ABC transporters are highly expressed in less differentiated subtypes and metastases. ABCA1, ABCB1 and ABCG2 are key players in BC chemoresistance. Restraining these transporters has evolved as a possible mechanism to reverse this phenomenon. Further, ABCB1 and ABCC1 are important in BC prognosis. Newer therapeutic approaches have been developed to target all these molecules to dysregulate their effect, reduce cell viability, induce apoptosis, and increase drug sensitivity. In the future, targeted therapy for specific genetic variations and upstream or downstream molecules can help improve patient prognosis.

Downregulation of miRNA-21 and cancer stem cells after chemotherapy results in better outcome in breast cancer patients.

Epigenetic modifications have been observed as a decline in miRNA-21 expression and breast cancer stem cell (CSC) population after 3 cycles of standard chemotherapy. The epigenetic response (miRNAs expression) and CSCs are also correlated in patients with Breast Cancer. In patients who tolerated chemotherapy well, miRNA-21 (non-coding RNA) expression decreased significantly after three cycles of chemotherapy. The miRNA-21 expression in breast cancer tissue was quantified by quantitative PCR (real-time PCR) using the standard protocol. In addition, breast CSCs (CD44+/CD24-) were also decreased in these patients. The miRNA-21 regulates cell division, proliferation, and autophagy of cancerous cells (as it targets phosphatase and tensin homolog/AKT/transcription factor EB/programmed cell death 4/autophagy-related protein 5 and chemotherapy also produces similar effects), thereby contributing to these benefits. Therefore, when all of the targets on genes have been explored by mimic miRNA, chemotherapy combined with anti-miRNA21 therapy may prove useful in the care of cancer patients.

FOXM1 mediates GDF-15 dependent stemness and intrinsic drug resistance in breast cancer.

BACKGROUND: Stemness, a key component of breast cancer (BC) heterogeneity, is responsible for chemoresistance. Growth differentiation factor-15 (GDF-15) induces drug resistance and stemness in BC cells. In this study, the expressions and interactions of GDF-15, FOXM1, and stemness (OCT4 and SOX2), and drug resistance (ABCC5) markers were evaluated in BC. METHODS AND RESULTS: 40 diagnosed BC patients and 40 healthy controls were included in this study. Serum GDF-15 was significantly raised (p < 0.001) in BC patients. Expressions of GDF-15, OCT4, SOX2, and FOXM1 in BC tissue and cell lines (MCF-7 and MDA-MB-231) were determined by RT-PCR, while phosphorylated AKT (p-AKT) was analyzed by Western blot. Not only were the fold change expressions higher in cancer tissue as compared to surrounding control tissue, but a higher expression was observed for all the genes along with p-AKT in MDA-MB-231 cells compared to MCF-7. Tissue GDF-15 was significantly associated with ABCC5 (p < 0.001), OCT4 (p = 0.002), SOX2 (p < 0.001), and FOXM1 (p < 0.001). To further analyze the signaling pathway involved in stemness and drug resistance in BC, GDF-15 knockdown was performed, which reduced the expression of p-AKT, FOXM1, OCT4 and SOX2, and ABCC5, whereas recombinant GDF-15 treatment reversed the same. In silico analyses in UALCAN revealed a similar picture for these genes to that of BC tissue expression. CONCLUSIONS: GDF-15 promotes stemness and intrinsic drug resistance in BC, possibly mediated by the p-AKT/FOXM1 axis.

Critical appraisal of epigenetic regulation of galectins in cancer.

Galectins are defined as the glycan-binding protein containing either one or two carbohydrate-binding domains and participate in various biological functions such as developmental processes, vascularisation programs, cell migration, and immune-regulation and apoptosis. Galectins are also linked to many diseases, including cancer. They are widely spread in extracellular and intracellular spaces, and their altered expression in cancer leads to tumor progression, metastasis, angiogenesis and stemness through different signalling pathways. Promoter methylation, microRNA, and histone modification constitute the epigenetic changes that regulate galectin activity in cancer. Our review discusses the concept of epigenetics in cancer and how the aforementioned factors i.e., promoter methylation, histone modification, change in miRNAs expression affect the glycomic changes in malignancies.

Leydig Cell Hyperplasia of Ovary - An Unusual Finding in Postneoadjuvant Chemotherapy Case of Primary Fallopian Tube Carcinoma.

A large number of high-grade serous ovarian carcinomas originate in the fallopian tubes. Neoadjuvant chemotherapy followed by surgery may lead to a number of chemotherapy-induced changes in the ovary, which may lead to an erroneous diagnosis. We present a rare case of a 55-year-old postmenopausal woman who was clinically diagnosed with carcinoma of the right ovary; on histopathologic evaluation after neoadjuvant chemotherapy, the primary site was found to be the right fallopian tube. The right ovary showed chemotherapy-related changes along with extensive Leydig cell hyperplasia. As the presence of Leydig cell hyperplasia in this setting is an unusual finding, it may pose a diagnostic dilemma for the pathologist; so an awareness of this entity is important to avoid misdiagnosis.

Serous Cystadenoma with Ectopic Adrenal Cell Rest of Ovary: A Rare Case Report.

Ectopic adrenal tissue is an uncommon entity in females. It is usually seen in male children, and the commonly involved sites are the kidney, retroperitoneum, spermatic cord, and paratesticular region. The ectopic adrenal gland in adults has been described in few studies only. Ectopic adrenal tissue was diagnosed as an incidental finding in histopathological examination of serous cystadenoma of the ovary. A 44-year-old female presented with a complaint of vague abdominal discomfort for the past few months. Ultrasound was suggestive of a left ovarian complex cystic lesion. The histopathological examination revealed serous cystadenoma with ectopic adrenal cell rest. Here, we present this case as it is a rare finding incidentally detected in a patient being operated on for a different pathology.

A Combined Analysis of Serum Growth Differentiation Factor-15 and Cancer Antigen 15-3 Enhances the Diagnostic Efficiency in Breast Cancer.

INTRODUCTION: Existing diagnostic biomarkers of breast cancer (BC) are limited by poor sensitivity. In this study, we evaluated the role of serum GDF-15 in early BC diagnosis, independently and in combination with CA15-3, a known blood biomarker of BC. MATERIAL AND METHODS: A total of 113 diagnosed, pre-therapy BC patients and 54 healthy controls were recruited. Clinical characteristics, TNM staging, and hormone receptor status of the patients were recorded. Serum GDF-15 and serum CA15-3 were measured by sandwich ELISA and chemiluminescence assay, respectively. RESULTS: The serum GDF-15 levels were significantly (p<0.001) elevated in BC patients compared to healthy controls and in patients with larger tumor size, advanced disease stage, and distant metastasis. ROC analysis revealed that at the cut-off of 525.77 pg/mL, GDF-15 had greater sensitivity than CA15-3. GDF-15 and CA15-3 performed better in combination than individually, with the combined test having an AUC of 0.85 and sensitivity and specificity of 0.63 and 0.98, respectively.Further, serum GDF-15 had a better predictive ability for early-stage BC compared to CA15-3. GDF-15 could independently diagnose BC patients after adjusting for age. CONCLUSION: We conclude that serum GDF-15 is a promising, robust marker for detecting early-stage BC. However, larger prospective studies are necessary to validate this claim.

Metaplastic breast carcinoma with extensive osseous differentiation.

Metaplastic breast carcinoma is a rare subtype of invasive breast carcinoma. Metaplastic carcinoma with osseous differentiation is exceptionally uncommon. Because of the heterogenous microscopy of the lesion, various clinical and radiological features are observed, leading to diagnostic difficulty. Herein, we present a case of a 43-year-old female with a recurrent breast lump, who was clinically diagnosed as a phyllodes tumor. However, histopathological examination revealed metaplastic carcinoma with extensive osseous differentiation.

Risk Stratification of Breast Fine-Needle Aspiration Biopsy Specimens Performed without Radiologic Guidance by Application of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Cytopathology.

BACKGROUND AND OBJECTIVE: The International Academy of Cytology (IAC) Yokohama system for reporting breast fine-needle aspiration biopsy (FNAB) cytopathology has been proposed to standardize breast FNAB reporting. The aim of this study was to categorize breast FNAB cases performed by palpation without radiological guidance according to the IAC system, establish the risk of malignancy (ROM) for the categories and assess the system's utility, pitfalls, and implications in low-resource/financial constraint settings. METHODS: A retrospective analysis of palpation-guided FNAB of breast lesions performed without radiological guidance between January 2016 and December 2019 was carried out and was correlated with follow-up biopsies wherever available. A total of 1,089 cases were recategorized using the IAC Yokohama system. Histopathology follow-up was available for 400 cases. The data were analysed for ROM, positive predictive value (PPV), and negative predictive value (NPV). RESULTS AND DISCUSSION: Out of 1,089 cases, 4.3% (n = 47) cases were categorized as insufficient, 82% (n = 893) as benign, 2.8% (n = 31) as atypical, 2.7% (n = 29) as suspicious of malignancy, and 8.2% (n = 89) as malignant. Some 400 cases had a follow-up biopsy, based on which, the ROM for the categories were 33.3%, 0.4%, 37.5%, 96%, and 100%. The NPV for the benign category was 99.6%. The PPV of the malignant category was 100%, that of combined suspicious of malignancy and malignant categories was 99%, and of combined atypical, suspicious of malignancy, and malignant was 90.6%. CONCLUSION: The IAC Yokohama system is useful in standardizing the reporting of cytopathology of breast lesions. FNAB with radiological guidance is ideal but in cases of finance/resource constraints, FNAB by palpation alone is satisfactory if the test result is in the benign, suspicious of malignancy, or malignant categories, which constitute 91.5% of the cases in this study. A repeat ultrasound-guided FNAB and/or core needle biopsy should be recommended for cases in the insufficient/inadequate or atypical categories.