Immunohistochemical expression of histone modification pattern in adult glioblastoma.

BACKGROUND: Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15 months. Genetic alterations have been studied in detail; however, additionally, there is now growing evidence on the role of epigenetic alterations in glioblastoma. Recently, histone modification patterns have been found to have a significant part in gene expression and prognosis. However, further research in this field is warranted to establish its role for the betterment of these patients with the deadly disease. AIMS: To determine the immunohistochemical expression of histone modifications like histone-3-lysine-18 acetylation (H3K18Ac) and histone-4-lysine 20 trimethylation (H4K20triMe) in glioblastoma patients. MATERIALS AND METHODS: This is a retrospective study of 48 glioblastoma patients who underwent surgery. Immunohistochemistry (IHC) for tri-methyl-histone-H4 (Lys20) (H4K20triMe) and acetyl-histone-H3 (Lys18) (H3K18Ac) was performed in paraffin-embedded tissues manually, and the expression was noted. Data on the mitotic index and overall survival was collected and statistically analyzed. RESULTS: The mean age was 50 years with a M: F ratio of 1.6:1. Out of 48 cases, 60% (28 cases) demonstrated positivity for H3K18Ac and 98% (46 cases) for H4K20triMe. The pattern of expression was nuclear with increased expression adjacent to necrosis and at the invasive front. The overall median Q score for H3K18Ac was 1/12 and for H4K20triMe was 6/12. No significant statistical significance was observed between histone expression, Ki67%, and overall survival. CONCLUSION: Histone modification patterns are being explored in detail in an array of tumors. They also have a potential role in glioblastoma for risk stratification and instituting appropriate treatment based on the prognosis. Epigenetic changes like histone modification patterns, in addition to genetics, can pave the way for a better molecular understanding of glioblastomas and provide hope in the future to improve the survival of these patients with deadly diseases.

Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure.

Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor-2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.

Characterizing colon cancer stages through optical polarimetry-assisted digital staining.

Tissue polarimetry has been gaining importance in extracting useful diagnostic information from the structural attributes of tissues, which vary in response to the tissue health status and hence find great potential in cancer diagnosis. However, the complexities associated with cancer make it challenging to isolate the characteristic changes as the tumor progresses using polarimetry. This study attempts to experimentally characterize the polarimetric behavior in colon cancer associated with various stages of development. Bulk and unstained sections of normal and tumor colon tissue were imaged in the reflection and transmission polarimetry configurations at low and high imaging resolutions using an in-house developed Mueller polarimeter. Through this study, we observed that the information about the major contributors of scattering in colon tissue, manifesting in depolarization and retardance, can be obtained from the bulk tissue and unstained sections. These parameters aid in characterizing the polarimetric changes as the colon tumor progresses. While the unstained colon section best indicated the depolarization contrast between normal and tumor, the contrast through the retardance parameter was more pronounced in the bulk colon tissue. The results suggest that the polarimetric "digitally stained" images obtained by Mueller polarimetry are comparable with the bulk tissue counterparts, making it useful for characterizing colon cancer tissues across different stages of development.

Results of Temporary Drainage of Poorly Functioning Kidneys With Ureteropelvic Junction Obstruction: Does the Histology of Persistent Poor Functioning Kidneys Indicate an Increased Risk of Hypertension?

OBJECTIVE: To review our experience with managing poorly functioning kidneys with ureteropelvic junction obstruction (PFK-UPJO) with differential renal function (DRF) <10% by a trial of temporary drainage, as the management of such kidneys is controversial. We also studied the histopathologic changes in the nephrectomy specimens of persistent PFK-UPJO, as tubulointerstitial damage may predispose to hypertension. METHODS: A retrospective review of cases undergoing treatment for unilateral UPJO over 5-year period in 2 centers was conducted. In PFK-UPJO, 4-6 weeks trial of drainage with double J stent or percutaneous nephrostomy was employed. Those kidneys that improved DRF to >10% underwent pyeloplasty, while persistent PFK underwent nephrectomy; the specimens were studied for interstitial fibrosis/tubular atrophy (IF/TA), arterial lesions, and arteriole lesions. RESULTS: Of 402 patients with unilateral UPJO that underwent surgical management, 17 (4.1%) had PFK-UPJO. After 4-6 weeks trial of drainage, 6 kidneys (35.2%) with improved DRF underwent pyeloplasty, while 11 kidneys with persistent PFK underwent nephrectomy; significant IF/TA, arterial, and arteriolar changes were noted in 9 (82%), 9 (82%), and 4 (36%) kidneys, respectively, including 7 kidneys in normotensive children. Two (11.7%) children had hypertension at presentation; 1 child remains hypertensive even after nephrectomy. CONCLUSION: In PFK-UPJO, trial of temporary drainage seems appropriate to decide plan of management; 35% of such kidneys improved function after drainage. Most persistent PFK demonstrated severe and irreversible histologic changes that may predispose to hypertension if they are preserved, and we suggest that such kidneys may be removed. Long-term follow-up of all preserved PFK-UPJO is strongly recommended.

Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics.

Cancer therapeutics face significant challenges due to drug resistance and tumour recurrence. The tumour microenvironment (TME) is a crucial contributor and essential hallmark of cancer. It encompasses various components surrounding the tumour, including intercellular elements, immune system cells, the vascular system, stem cells, and extracellular matrices, all of which play critical roles in tumour progression, epithelial-mesenchymal transition, metastasis, drug resistance, and relapse. These components interact with multiple signalling pathways, positively or negatively influencing cell growth. Abnormal regulation of the Wnt signalling pathway has been observed in tumorigenesis and contributes to tumour growth. A comprehensive understanding and characterisation of how different cells within the TME communicate through signalling pathways is vital. This review aims to explore the intricate and dynamic interactions, expressions, and alterations of TME components and the Wnt signalling pathway, offering valuable insights into the development of therapeutic applications.

Grossing and reporting of radical prostatectomy specimens: An evidence-based approach.

Radical prostatectomy (RP) constitutes the primary treatment option for patients with clinically localized, biopsy-proven prostate cancer that requires local treatment with curative intent. Accurate reporting of radical prostatectomy specimens is required to guide further risk stratification and management of patients. Hence, for the handling and reporting of RP specimens, a standardized protocol should be followed. Many general pathologists may not be well-versed with the guidelines for the handling of radical prostatectomy specimens. This article discusses a detailed approach to grossing techniques, including specimen description, fixation requirements, gross cut-up, and reporting of the grade and stage of RP specimens. This will enable the pathologist to aid in multidisciplinary management.

Detection and Estimation of Age of Injuries in Fresh Bodies Using Immunohistochemistry.

ABSTRACT: A cross-sectional study of the wound age estimation from the forensic skin wound samples was performed immunohistochemically with a sample size of 40 (n = 40). The samples were segregated according to the appropriate stages of wound healing with the help of hematoxylin-eosin staining. Later, they were subjected to immunohistochemistry staining with anti-AQP3 antibody. Quantification of the expression of AQP3 in the injured and uninjured formalin-fixed skin tissues was done semiquantitatively and manually under 400× magnifications. The AQP3-positive cells were correlated with the duration of injury, and the results were statistically analyzed. More AQP3 expressions were found in the proliferative phase than the inflammatory and maturation phase of wound healing. Neither the diversity in age group nor the sex differentiation showed any specific correlation with the expression of keratinocytic aquaporin cells. Likewise, parameters such as the type of injury, mode of injury, and the postmortem interval also did not show any significant relationship with the expression of the aquaporin positivity. Thus, it is revealed that skin wounds between 5 and 10 days expressed aquaporin cell numbers of more than 300. Hence AQP3 estimation helps in determining the time since injury with a more accuracy.

Improved Diagnosis through Diastolic Hyperemia-Free Ratio (DFR) over Fractional Flow Reserve (FFR) in Intermediate Coronary Lesions.

Objectives: To compare the fractional flow reserve (FFR) and diastolic hyperemia-free ratio (DFR) measurements in a population with intermediate coronary artery stenosis and improve the diagnosis. Background: Visual assessment of coronary artery stenosis severity, particularly in intermediate lesions, is prone to errors in decision-making. FFR provides a reliable assessment of functional severity in these cases but requires hyperemia induction by adenosine, which has side effects and increased cost. DFR is a novel hyperemia-independent index, which could be used as an alternative to adenosine-based hyperemia induction. Methods and Results: Between September 2019 to March 2020, 25 patients with 38 intermediate coronary stenotic lesions were included in the study. All patients underwent assessment of whole cycle Pd/Pa (ratio of distal coronary pressure to proximal aortic pressure), DFR and FFR. Mean whole cycle Pd/Pa, DFR and FFR were 0.93±0.06, 0.88±0.09, and 0.85±0.08, respectively. A significant positive correlation between DFR and FFR [r = 0.74; p<0.001] was observed. Receiver operating characteristic analysis showed an area under the curve of 0.90. DFR-only strategy with a treatment cut-off of ≤0.89 showed a diagnostic agreement with the FFR-only strategy in 74% of lesions, with a sensitivity of 54%, specificity of 82%, a positive predictive value of 60%, and a negative predictive value of 79%. Conclusions: Real-time DFR measurements show a clinically reliable correlation with FFR. Hence, using DFR is likely to avoid adenosine administration as well as reduce the cost and procedural time. Further studies with a larger sample size would be ideal to evaluate specific cut-off values and endpoints.

Immunohistochemical Analysis of PD-1 and FOXP3 in Tumor-Infiltrating Lymphocytes in Human Gliomas.

Introduction Despite the growing advances in molecular research and therapeutics, gliomas continue to be highly invasive and progressive tumors. There is still a need for the development of reliable prognostic biomarkers for effective therapeutic intervention. This study aims to investigate the extent of immunosuppression in glial tumors by analyzing the clinical significance of the expressions of PD-1 and FOXP3 in gliomas. Methods This is a retrospective study from 52 glioma patients who underwent surgery. Immunohistochemistry (IHC) for PD-1 and FOXP3 was performed on paraffin-embedded tissue sections manually and their expressions were noted. Data on IDH1 mutational status and mitotic index was collected and statistically analyzed. Results Immunohistochemical analysis showed that out of 52 cases, 71.15% (37/52) demonstrated cytoplasmic positivity for PD-1 and 73.1% (38/52) of the cases for nuclear FOXP3 expression. Statistical analysis suggested that elevated PD-1 and FOXP3 expressions were significantly correlated with tumor grade and increased mitotic index (P<0.05 for both the markers). Conclusion Concurrent use of checkpoint inhibitors along with other treatment modalities is being studied in a variety of solid tumors. Expressions of negative immune regulators like PD-1 and Foxp3 can pave way for a better understanding of the extent of immunosuppression in the glial tumor environment, which is imperative to formulate new therapeutic approaches.

Immunohistochemical Evaluation of Notch1 in Ovarian Tumours and Its Prognostic Implications.

BACKGROUND: Ovarian cancer is the fifth most common malignancy among women and the second most common gynaecological malignancy. Surface epithelial ovarian tumours constitute two-thirds of all ovarian tumours. Most high-grade serous carcinoma patients gain an initial complete response but eventually succumb to relapse and death leaving the overall survival grim. Therefore, new regimens targeting the pathways involved in metastasis and chemoresistance are essential for the development of more effective therapies. Notch signalling is one of the pleiotropic signalling pathways that plays a key role in differentiation and tissue morphogenesis. It has been observed that this Notch signalling pathway is seen to be deregulated in various cancers. It is thought to have an oncogenic role in ovarian cancer. Our objective in this study is to evaluate the immunohistochemical expression pattern of Notch1 in surface epithelial ovarian tumours and its correlation with the clinicopathological profile. METHODS: This study includes a total of 100 cases of borderline and malignant surface epithelial ovarian tumours. Clinical data of the patients were obtained from the medical records section. HPE slides were examined and one representative paraffin block was selected for each patient. IHC of Notch1 was performed and analyzed. The staining pattern for Notch1 was calculated using the Q score. RESULTS: Immunohistochemistry (IHC) evaluation of Notch1 in surface epithelial ovarian tumours in this study showed an increased intensity of Notch1 staining in high-grade serous malignant tumours. The grading and staging of tumours were compared with Notch1 expression. Statistical analysis was performed using Spearman Rank order correlation analysis. There was a significant correlation (0.01 level, two-tailed) between the grading and staging of ovarian tumours and Notch1 expression. CONCLUSION: Assessing Notch1 expression in ovarian cancer by IHC is a useful tool in view of its clinical applications, development of targeted therapies and as a marker of prognosis. The intensity of the Notch1 stain appears to be directly proportional to the grade of tumour. This may offer a potential targeted therapy against the Notch signalling pathway in tumours that strongly express Notch1.

Clinico-Pathological and Radiological Spectrum of Mediastinal Masses in a Tertiary Care Center: A Cross-Sectional Study.

Introduction The phrase "mediastinal mass" refers to a mass within the mediastinum. About 50% of all mediastinal masses, including teratoma, thymoma, lymphoma, and thyroid illness, are anterior mediastinal tumors. Data on the mediastinal mass in India are relatively sparse, especially in this region, compared to those from other countries. Mediastinal masses are very infrequent lesions that might occasionally present a diagnostic and therapeutic challenge to the doctor. The current study describes the socio-demographic characteristics, symptoms, diagnosis, and location of mediastinal mass among the study participants. Methodology We carried out a retrospective, cross-sectional study in a tertiary care center in Chennai for three years. We included patients with an age above 16 years who visited the tertiary care center in Chennai during the study period. We included all patients with a mediastinal mass diagnosed by CT scan, with or without signs and symptoms of mediastinal compression. Patients under the age of 16 and those with insufficient data were both excluded from the study. As per the universal sampling technique, we included all the patients who met the eligibility criteria during the study period (three years) as study subjects. By using the hospital records, we collected all data about the patients like socio-demographic data, presenting complaints, past history, x-ray findings, and co-morbidities. Similarly, we recorded blood parameters, pleural fluid parameters, and histopathological reports from the laboratory register. Results The mean age of the study participants was 41.11 years, with a high proportion of patients belonging to the age group of 21 to 30 years. Over 70% of the study participants were male. Only about 54.5% of the study participants had symptoms because of a mediastinal mass. The most common local symptom felt by the patients was dyspnea, followed by a dry cough. Weight loss was the most common symptom for the patients. Most study participants (47.7%) had seen a doctor within one month of the onset of symptoms. About 4.5% of the patients had pleural effusion, as diagnosed by x-ray. Most of the study participants had a mass in the anterior mediastinum, followed by the posterior mediastinum. Most of the participants (15.9%) had non-caseating granulomatous inflammation suggestive of sarcoidosis.  Conclusion The most common tumor found in our study was lymphoma, which was followed by non-caseating granulomatous disease and thymoma. Anterior compartments are most commonly involved. We observed the most common presentation in the third decade of life with a male to female ratio of 2:1, with dyspnea being the most common symptom, followed by a dry cough. Our study found 4.5% of the patients had pleural effusion as a complication.

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence.

Ovarian cancers are tumors that originate from the different cells of the ovary and account for almost 4% of all the cancers in women globally. More than 30 types of tumors have been identified based on the cellular origins. Epithelial ovarian cancer (EOC) is the most common and lethal type of ovarian cancer which can be further divided into high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. Ovarian carcinogenesis has been long attributed to endometriosis which is a chronic inflammation of the reproductive tract leading to progressive accumulation of mutations. Due to the advent of multi-omics datasets, the consequences of somatic mutations and their role in altered tumor metabolism has been well elucidated. Several oncogenes and tumor suppressor genes have been implicated in the progression of ovarian cancer. In this review, we highlight the genetic alterations undergone by the key oncogenes and tumor suppressor genes responsible for the development of ovarian cancer. We also summarize the role of these oncogenes and tumor suppressor genes and their association with a deregulated network of fatty acid, glycolysis, tricarboxylic acid and amino acid metabolism in ovarian cancers. Identification of genomic and metabolic circuits will be useful in clinical stratification of patients with complex etiologies and in identifying drug targets for personalized therapies against cancer.

Biphasic squamoid alveolar renal cell carcinoma: A rare entity with an even rarer presentation as cutaneous metastases - A case report.

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly emerging distinct and rare morphologic variant of renal cell carcinoma (RCC). Morphological, immunohistochemical, and molecular data have shown that BSARCC is closely related to papillary RCC type 1. We report a case of Biphasic squamoid alveolar renal cell carcinoma with a rare presentation as cutaneous metastases. This variant tends to show an aggressive behavior. Hence, accurate histopathological diagnosis can help in effective treatment and for close follow-up of the patients.

Differentiation of urothelial carcinoma in histopathology images using deep learning and visualization.

Artificial Intelligence is a tool poised to transform healthcare, with use in diagnostics and therapeutics. The widespread use of digital pathology has been due to the advent of whole slide imaging. Cheaper storage for digital images, along with unprecedented progress in artificial intelligence, have paved the synergy of these two fields. This has pushed the limits of traditional diagnosis using light microscopy, from a more subjective to a more objective method of looking at cases, incorporating grading too. The grading of histopathological images of urothelial carcinoma of the urinary bladder is important with direct implications for surgical management and prognosis. In this study, the aim is to classify urothelial carcinoma into low and high grade based on the WHO 2016 classification. The hematoxylin and eosin-stained transurethral resection of bladder tumor (TURBT) samples of both low and high grade non-invasive papillary urothelial carcinoma were digitally scanned. Patches were extracted from these whole slide images to feed into a deep learning (Convolution Neural Network: CNN) model. Patches were segregated if they had tumor tissue and only included for model training if a threshold of 90% of tumor tissue per patch was seen. Various parameters of the deep learning model, known as hyperparameters, were optimized to get the best accuracy for grading or classification into low- and high-grade urothelial carcinoma. The model was robust with an overall accuracy of 90% after hyperparameter tuning. Visualization in the form of a class activation map using Grad-CAM was done. This indicates that such a model can be used as a companion diagnostic tool for grading of urothelial carcinoma. The probable causes of this accuracy are summarized along with the limitations of this study and future work possible.

Sacrococcygeal mass in a 3-year-old unfolding as Dabska tumor-A very rare entity.

ABSTRACT: Papillary intralymphatic angioendothelioma, previously known as Dabska's tumor, is a very rare entity in children involving the skin and soft tissue. It is a low grade tumor characterized by papillary endovascular proliferations of atypical endothelial cells and anastomosing vascular channels in the dermis. We present a 3-year-old male child, with a history of swelling and mild pain in the right upper gluteal region, progressive in nature for 1 month duration. On examination, the swelling was soft to firm and mildly tender. Radiology was suggestive of Sacro-coccygeal teratoma. Grossly, it was an ill-defined grey brown lesion measuring 3.5 × 3 × 2 cm. Microscopy showed lesion arranged in papillary pattern with slit like vascular channels and intra luminal proliferations of hobnail like endothelial cells. Morphology and immunohistochemical studies revealed a diagnosis of Papillary intralymphatic angioendothelioma.

Laryngeal Lymphoma in a Child - Case Report and Review of Literature.

Introduction: Head and neck is the second most common region for lymphomas. Extranodal lymphomas of the larynx are rare in the pediatric population. Non Hodgkin Lymphoma (NHL) of the larynx is common in the supraglottic region as its rich in lymphoid tissue. They may present with dysphagia, dysphonia, snoring and progressive respiratory distress. Early visualization of the larynx is essential in such cases for appropriate diagnosis to improve the survival rates. Case Report: We present a case of 9 year old boy who presented with a change in voice, snoring and feeding difficulties for one year. Video laryngoscopy revealed globular mass arising from the epiglottis. He underwent excision biopsy and by immunohistochemistry was diagnosed to have diffuse large B cell lymphoma. He was treated with chemotherapy and the child is clinically well in the follow-up, 1 year after the completion of therapy. Conclusions: Although primary lymphomas of the larynx in children are rare, a high index of clinical suspicion is warranted to avoid diagnostic delays to initiate appropriate management to have better outcomes.

Preoperative neutrophil-lymphocyte ratio/platelet-lymphocyte ratio: A potential and economical marker for renal cell carcinoma.

Background: Emerging evidences have elucidated the crucial role of inflammation in carcinogenesis and tumor progression. In the recent years, many inflammatory biomarkers showed promising prognostic factors in renal cell carcinoma (RCC). We intended to evaluate the significance of one such inflammatory factor which is potential, noninvasive, simple, as well as economical. The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in RCC patients have shown favorable results. Objective: The objective was to assess the prognostic role of NLR/PLR in the advanced stage and high-grade RCC. Subjects and Methods: This is a retrospective study. Ethical clearance was obtained from the institute ethics committee. One hundred and fifty histopathologically proven RCC cases during the period of January 2010-September 2018 were chosen from the pathology department and corresponding blood reports were obtained from the medical records department. We divided the cases based on their staging and grading. NLR/PLR values were calculated using formulas. Statistical Analysis: Statistical analysis was done using R software. Data were expressed as mean ± standard deviation, median, and percentage. Independent t-test, Mann-Whitney test, and Chi-square test were used. P < 0.05 was considered statistically significant. The receiver operating characteristic curve (ROC) was plotted to assess the sensitivity of NLR/PLR. Results: The elevated NLR/PLR values showed a significant relation with high-grade and advanced stage RCC. The ROC curve proved the accuracy of NLR/PLR in the advanced stage and high-grade RCC. Limitations: A multicentric, prospective study can be planned in the future. Follow-up studies are needed to assess their prognostic role. Conclusion: NLR/PLR values can become part of routine investigations for all RCC patients. The values may help to estimate pathological outcomes, chance of recovery, recurrence, and survival rates.

Comparison of p63 immunohistochemistry and shear wave elastography in the diagnosis of indeterminate breast lesions: A prospective study.

Purpose: To evaluate the accuracy of breast shear wave elastography (SWE) and p63 immunohistochemistry (IHC) in the diagnosis of indeterminate breast lesions. Methods: Based on detailed clinical examination and a combination of X-ray mammography/B-mode ultrasound with SWE, a total of 40 patients with breast lumps (BI-RADS 4) were included. Patients with previous diagnosis of breast cancer and a previous history of surgery, chemotherapy, or radiotherapy in the same breast as the present lesion were excluded. Core needle biopsy of the breast lesion was performed, and p63 IHC staining was performed. A final histopathological report of the definitive procedure was considered as the gold standard. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy were calculated for each modality. Results: The mean age of the patients included in the study was 50.85 ± 13.53 years. Of the 40 patients recruited, 23 were clinically malignant and 17 were benign. The sensitivity, specificity, PPV, NPV, and accuracy of SWE were 91.3%, 94.1%, 95.5%, 88.9%, and 92.5% and those of p63 IHC were 95.7%, 100%, 100%, 94.4%, and 97.5%, respectively. Overall, the parametric values were higher for p63 IHC as compared to clinical examination and elastography. The area under the ROC curve (AUC) for p63 IHC (.978) was higher than those for SWE (.927) and clinical examination (.898). Conclusion: SWE and p63 IHC are highly reliable novel modalities that demonstrate enhanced diagnostic accuracy of indeterminate breast lesions aiding in the early initiation of appropriate treatment and reducing the number of women subjected to biopsy or short-term follow-up for benign-appearing solid breast lesions.

Role of CTLA4 immunohistochemistry in the diagnosis of colon cancers.

Background: There are a wide range of diagnostic markers for colorectal cancers like detection of mutated KRAS, TP53, and APC genes. However, genetic and immunological factors have also been attributed to the cancer prognosis. The present study was carried out to evaluate the expression of CTLA-4 in colorectal cancers. Methods: This cross-sectional study was carried out among 30 resected specimens of colorectal cancer. Paraffin blocks were made on samples from tumor areas along with adjacent normal areas. Immunohistochemistry for CTLA-4 was done on the sections along with controls. Gross findings were recorded from the blocks. Blocks with section containing normal epithelium and tumor were chosen for immunohistochemistry. Results: Overexpression of CTLA-4 was observed in 43.3% of the tumors. There was a significantly high tumor infiltration among those specimens showing overexpression of CTLA-4. The observed difference was statistically significant (P < 0.05). On comparing the grade of the tumor with intensity of CTLA4 uptake, it was observed that majority of the well-differentiated tumors (66.7%) had an intensity of 1+ whereas majority of the poorly differentiated tumors had an intensity of 3+ (66.7%). Conclusion: The present study has demonstrated overexpression of CTLA-4 in colorectal cancer specimens, and also highlighted the potential scope for anti-CTLA-4 agents like Ipilimumab in cancer therapy. The need for further evaluation to examine five-year survival with such immunotherapies is essential to document candid therapeutic recommendations for colorectal cancers.

Zinc transporter LIV1: A promising cell surface target for triple negative breast cancer.

Breast cancer is one of the leading causes contributing to the global cancer burden. The triple negative breast cancer (TNBC) molecular subtype accounts for the most aggressive type. Despite progression in therapeutic options and prognosis in breast cancer treatment options, there remains a high rate of distant relapse. With advancements in understanding the role of zinc and zinc carriers in the prognosis and treatment of the disease, the scope of precision treatment/targeted therapy has been expanded. Zinc levels and zinc transporters play a vital role in maintaining cellular homeostasis, tumor surveillance, apoptosis, and immune function. This review focuses on the zinc transporter, LIV1, as an essential target for breast cancer prognosis and emerging treatment options. Previous studies give an insight into the role of LIV1 in fulfilling the most important hallmarks of cancer such as apoptosis, metastasis, invasion, and evading the immune system. Normal tissue expression of LIV1 is limited. Higher expression of LIV1 has been linked to Epithelial-Mesenchymal Transition, histological grade of cancer, and early node metastasis. LIV1 was found to be one of the attractive targets in the therapeutic hunt for TNBCs. TNBCs are an immunogenic breast cancer subtype. As zinc transporters are known to serve as the metabolic gatekeepers of immune cells, this review bridges tumor infiltrating lymphocytes, TNBC and LIV1. In addition, the suitability of LIV1 as an antibody-drug conjugate (Seattle genetics [SGN]-LIV1A) target in TNBC, represents a promising strategy for patients. Early clinical trial results reveal that this novel agent reduces tumor burden by inducing mitotic arrest, immunomodulation, and immunogenic cell death, warranting further investigation of SGN-LIV1A in combination with immuno-oncology agents. Priming the patient's immune response in combination with SGN-LIV1A could eventually change the landscape for the TNBC patient population.