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Abstract Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.

The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from 10 cases each of GBC and inflammatory lesions, with technical duplicates. Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan–Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real time-polymerase chain reaction (RT-PCR). Out of 5,714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables. Prognostic factors such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival. Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.

Abstract Background Breast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown. Methods This study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein. Results In our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position. Conclusions The current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC.

Chronic inflammation in the gallbladder leading to persistent epithelium damage promotes invasive cancer. The study aimed to assess the prognostic value of PDL1 and CA19-9 markers in cancer/inflammatory lesions of the gallbladder. A total of 29 cases (19 cancer and 10 inflammatory) were included. The PDL1 protein concentration level and mRNA expression were assessed in the tissues’ lysates by ELISA and real-time PCR, respectively. PDL1 and CA19-9 concentration levels were compared and statistically related with clinico-pathological variables. The PDL1 protein level and its relative mRNA expression were correlated. Kaplan–Meir survival and Cox regression analyses were conducted for predicting prognosis. This study investigated the PDL1 and CA19-9 marker expression in both cancer and inflammatory cases of the gallbladder (p = 0.48 and p = 0.17 respectively). PDL1 protein expression was significantly associated with the hormonal profile of the cases (p = 0.04) at an optimum cut-off value of 13 pg/mL, while the CA19-9 marker expression was correlated with the status of liver metastasis (p = 0.0043) and size of the tumor (p = 0.004). A low PDL1 concentration was found when compared to the CA19-9 level among cancer cases (p = 0.12) and proportional in the inflammatory lesions (p = 0.63). A significant positive correlation was found between the PDL1 protein and its relative mRNA expressions in the inflammatory lesions (p = 0.029) when compared to cancer cases (p = 0.069). Our results showed that a protein-based assay for PDL1 expression would be more sensitive compared to RNA based assays for GBC risk stratifications. Overall survival was predicted with CA19-9 and PDL1 levels (p = 0.0074, p = 0.23, respectively). PDL1 and CA19-9 may act as a probable predictor of a poor prognosis in gallbladder cancer (GBC) cases.

Germ cell tumour (GCT) is the most common testicular tumour that commonly presents as a painless mass. Bone marrow metastasis in cases of testicular GCT is rare; only few case reports are available till date in the literature. Here an adult male presented with an intra-abdominal mass in right iliac fossa with inguinal lymphadenopathy with a deranged kidney function test. Bone marrow (BM) aspirate smear revealed metastatic tumour cells, but BM-biopsy was unremarkable. High serum Beta - HCG (38286 mIU/L) pointed towards germ cell lesion. Lymph node biopsy along with immunomarkers confirmed metastatic foci from germ cell tumor and managed as per standard protocol. Rarely BM aspirate is seen positive for malignancy, while biopsy turns out to be negative. Secondly, BM metastasis of GCT should be considered while dealing with cases like this. Informed consent: This is certified that the informed consent has been obtained from the patient.

Introduction: Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. Method: Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. Result: Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL-2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.

Glucocorticoid (GC), such as prednisolone, is an essential component of multidrug chemotherapy regimen for pediatric acute lymphoblastic leukemia (ALL). Resistance to GC in leukemia cells is associated with disease progression and poor prognosis. Despite the extensive use of GC for many years, molecular mechanisms underlying its resistance in ALL have not been fully uncovered. Recent studies have shown a potential role of EMP1, CASP1, and NLRP3 genes in prednisolone response. In this study on 148 pediatric B-ALL patients, we studied these three genes to assess their association with prednisolone response measured by day 8 blast count after 7 days of induction therapy with prednisolone. Intriguingly, ALL samples exhibited higher expression of EMP1 along with a low expression of CASP1 and NLRP3 compared to disease free normal bone marrow collected from patients with solid tumors. Among the three analyzed genes, only EMP1 was found to be overexpressed in prednisolone poor responders (p=0.015). Further, a comparison of gene expression between cytogenetic subtypes revealed higher expression of EMP1 in BCR-ABL subtype. Expression of EMP1 in multiple gene expression datasets was used for gene set enrichment analysis, which revealed TNF-α, IL-2-STAT5 signaling, inflammatory responses and hypoxia as the major positively associated pathways and E2F targets as negatively associated pathways. Interestingly, the clinical remission rate was higher in CASP1 high patients (p=0.048). In univariate survival analysis, higher EMP1 expression was associated with poor prognostic measures while higher expression of NLRP3 and CASP1 was associated with better prognostic measures in our data. Further, multivariate analysis revealed an independent association of high CASP1 and NLRP3 with a better prognosis. This study strengthens the available evidence that mRNA expression of EMP1, CASP1, and NLRP3 may serve as potential biomarkers for risk stratification of pediatric B-ALL patients.

Waldenstrom macroglobulinemia (WM) is a variant of lymphoplasmacytic lymphoma. In WHO classification of hematolymphoid malignancy 2016, WM has been placed in between lymphoma and plasma cell myeloma under the broad heading “Neoplasms of mature lymphocytes”. This is a rare and slowly progressive disorder, which needs therapy only when symptoms appear. The average age of diagnosis is 60–70 years. WM may progress to lymphoma in 2% cases per year. Here, we are discussing a case of WM having typical findings of this rare disease, who presented with 10%–12% plasma cell in bone marrow aspirate smear, high immunoglobulin M, high beta 2 microglobulin, bilateral axillary lymphadenopathy and gastrointestinal bleeding. At present, the patient is on chlorambucil plus prednisolone therapy and is doing well. Typically, this case presented with lesions of herpes zoster, which makes this case further uncommon.

Ovarian Cancer (OC) is the most fatal condition among all gynaecologic malignancies. The survival rate of early and advance stage of OC is 80-90% and 15-20% respectively. This data constitutes the need of a novel biomarker for early diagnosis, which may distinguish malignant tumours from benign ovarian cysts. Presently in practice there are three screening techniques: bimanual pelvic examination, serum Cancer Antigen (CA) 125 and transvaginal ultrasound. Bimanual pelvic examination can detect only 1 in 10,000 ovarian cancers in women presenting to the clinic. CA 125 is raised in 80% of cases of ovarian carcinoma; however, if the carcinoma is limited to ovary, the raised value is seen only in 50% of women. It is mainly useful in postmenopausal women. Ultrasonography also lacks specificity and sensitivity, apart from being costly as a screening test. Studies are going on for search of a biomarker, which may complement CA 125. Most common among these are Human Epididymis Protein 4 (HE4), Thrombopoietin (TPO), CA19-9, human kallikrein 10, human kallikrein 6, osteopontin, claudin 3, DF3 (murine monoclonal antibody), vascular endothelial growth factor, MUC1, mesothelin etc. In 2008, FDA approved the use of HE4 assay for monitoring of progressive disease in patients with epithelial ovarian cancer. Similarly TPO also holds the promise of being a biomarker to complement CA125 and many studies are indeed available to support the association of TPO and OC. In this review article we have summarised and analysed such studies.

Introduction: The incidence of soft tissue tumours, especially the frequency of benign tumours relative to malignant ones, is nearly impossible to determine accurately. Benign soft tissue tumours outnumber malignant tumours by a wide margin. Objectives: The main purpose of this study was to look into the clinicopathological profile of benign soft tissue tumour in terms of hospital incidence of age, sex, site distribution and comparison of histological types of benign soft tissue tumours with other similar studies. Materials and Methods: The operated specimens or biopsy material of benign soft tissue tumours received from January, 2010 to July, 2010 in the Department of Histopathology of our hospital, were studied in detail. Age and sex incidence, site of lesion, clinical features, gross and microscopic appearance were carefully studied. Results: In our study, most common benign soft tissue tumour was lipoma (50.8%) followed by hemangioma (17.5%) which in turn was followed by neurofibroma, angiofibroma & schwannoma. Most common age group for benign soft tissue tumour were 31-40y (27.5%) followed by 21-30y (22.5%). Overall a male predominance was seen with 60.83% in males. The most common site of occurrence of benign soft tissue tumour overall was found to be trunk (25%), followed by upper extremities (21.7%), lower extremities (17.5%) and nose and nasopharynx (10.8%) in that order. Conclusion: With our study, we were able to reassess the clinical profile of soft tissue tumours and their different types with respect to age, sex, site distribution.

T‐cell acute lymphoblastic leukemia (T‐ALL) is a genetically heterogeneous disease, characterized by an abnormal transformation of T cells into highly proliferative leukemic lymphoblasts. Identification of common genetic alterations has provided promising opportunities for better risk stratification in T‐ALL. Current treatment in T‐ALL still poses the major challenge of integrating the knowledge of molecular alterations in the clinical setting. We utilized the Multiplex Ligation Dependent Probe Amplification (MLPA) method to determine the frequency of common copy number alterations (CNAs) in 128 newly diagnosed T‐ALL patients. We also studied the association of these CNAs with patient's clinical characteristics and survival. The highest frequency of deletion was observed in CDKN2A (59.38%), followed by CDKN2B (46.88%), LMO1 (37.5%), and MTAP (28.12%). PTPN2 (22.66%), PHF6 (14.06%), and MYB (14.06%) had the highest number of duplication events. A total of 89.06% patients exhibited CNAs. STIL::TAL1, NUP214::ABL1, and LMO2::RAG2 fusions were observed in 5.47%, 3.12%, and 0.78% of patients, respectively. CDKN2A, CDKN2B, and PTPN2 gene deletions were mainly observed in pediatric patients, while CNAs of NF1 and SUZ12 were observed more frequently in adults. In pediatric patients, alterations in CDKN2B, CASP8AP2, and AHI1 were associated with poor prognosis, while SUZ12 and NF1 CNAs were associated with favorable prognosis. In adult patients, ABL1 CNA emerged as an independent indicator of poor prognosis. The observed molecular heterogeneity in T‐ALL may provide the basis for variations observed in clinical response in T‐ALL and MLPA based CNA detection may help in risk stratification of these patients. [ABSTRACT FROM AUTHOR]