Histopathological Markers Research Articles

Effect of burnt tire-ash (water-soluble fraction) on blood and histopathological markers in Clarias gariepinus

Aquatic habitats serve as pollutant reservoirs and experience massive pollution disasters due to anthropogenic pressure. The effect of the Water-Soluble Fraction (WSF) of burnt tire ash (BTA) was investigated on Clarias gariepinus juvenile using blood biomarkers as well as liver and gill histology. The model fish were exposed to 5 % (0.56 g/L), 10 % (1.12 g/L) and 20 % (2.24 g/L) of 96-hr LC50 (11.2 g/L) value of BTA sub-chronic doses during the experiment. Hematological indices, the liver, and gill histology were studied throughout the 28-day exposure study, which was followed by a 14-day post-exposure trial. The studies revealed that BTA-exposed fish had reduced red blood cells, packed cell volume, and hemoglobin levels with time, whereas white blood cells and leukocyte numbers increased. Concentration-dependent histopathologic abnormalities such as hyperplasia, telangiectasis, hemorrhage, desquamation, lamellar edema, and vacuolation were observed in the gill of the affected fish, in contrast to the control. Likewise, the presence of histopathologic abnormalities in the liver of BTA-exposed fish, such as vacuolar degeneration, hyperplasia, dilated portal vein, pyknotic nucleus formations, hypertrophy hepatocytes, and aggregated macrophages, was concentration-dependent. Following apparent histologic deformities that persisted in the tissues after recovery, healing from BTA exposure was only partial. C. gariepinus is an essential bioindicator of burnt tire ash’s ecotoxicological impact. Point and non-point traces of burnt-tire ash to the aquatic systems may harm aquatic animal species, thus necessitating preventative actions.

Decreased survival in patients with pancreatic cancer may be associated with an increase in histopathological expression of inflammasome marker NLRP3.

Pancreatic cancer is a malignant neoplasm that, despite its low frequency, has a 5-year survival rate of less than 10%. The study of different histopathological markers has allowed a better understanding of the onset and development of this type of tumor as well as facilitating an approach to clinical variables based on their diagnostic, prognostic, and predictive value. In this sense, the NLRP3 protein of the inflammasome has been shown to be a component of great relevance in the initiation and progression of pancreatic cancer, although the value of this biomarker in patients has not yet been clarified. In this study, we selected 41 patients with pancreatic cancer and followed them for 60 months (5 years), evaluating their NLRP3 expression using immunohistochemical techniques. Furthermore, by performing Kaplan-Meier curves, we evaluated the survival of these patients in relation to their NLRP3 expression. Our results show that a significant percentage of our cohort had high expression of this component (90.74%) and that there is an inverse relationship between the expression of NLRP3 and patient survival. High levels of NLRP3 expression are related to lower survival and worse prognosis in these patients, possibly due to an ineffective immune system response and increased tumor-promoted inflammation. Future studies should be aimed at confirming these results in larger groups and evaluating various clinical strategies based on this knowledge.

Sublethal toxicity of carbofuran in cattle egret (Bubulcus ibis coromandus): hematological, biochemical, and histopathological alterations.

This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.

Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways.

Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125) for Prediction of Optimal Primary Surgery in Non-Mucinous Epithelial Ovarian Cancer.

To determine the relationship between pre-operative HE4 and CA125 levels in non-mucinous epithelial ovarian cancer cases (EOC) and outcomes of primary surgery for prediction of optimal surgery. A retrospective study was performed on non-mucinous EOC who underwent primary surgery at King Chulalongkorn Memorial Hospital from 2016 to 2020. Demographic and clinical characters were collected. Histopathology and pre-operative tumor markers namely HE4 and CA125 were also recruited. Primary surgical outcomes were classified as optimal (OS) and suboptimal surgery (SS). One hundred and seventy patients were enrolled in the study. There were 130 and 40 cases in OS and SS, respectively. Average age and body mass index (BMI) of EOC were 54.2 years old and 23.1 Kg/m2, respectively. Both groups had comparable demographic characteristics. Two-thirds (103/170) and one-third (63/170) had early stage and clear cell histopathology, respectively. The median level of HE4 were 118.60 and 603.45 pmol/L in OS and SS, respectively. OS and SS had average CA125 at 146.95 and 814.70 U/L, respectively. The best cut-off point of HE4 and CA125 less than 170.95 pmol/L and 316.4 U/mL gave predicting OS with area under curve (AUC) at 0.78 and 0.75, respectively. HE4 and CA125 cut-off point had sensitivity, specificity, positive predict value (PPV) and negative predictive value (NPV) at percentage of 60.8/60.8, 87.5/82.5, 94.1/91.9 and 40.7/39.3, respectively. HE4 and CA125 of non-mucinous EOC among OS had significantly less than SS and could be the predicting of optimal surgery.

Adipose tissue derived stem cell secretome induces motor and histological gains after complete spinal cord injury in Xenopus laevis and mice

Mesenchymal stem cell-based therapies have been studied for spinal cord injury (SCI) treatment due to their paracrine action upon damaged tissues. MSCs neuroregenerative role may relate to the contents of their secretome in anti-inflammatory cytokines and growth-permissive factors. We propose using the secretome of MSCs isolated from the adipose tissue—adipose tissue-derived stem cells (ASCs) as a cell-free based therapy for SCI. In vivo studies were conducted in two SCI models, Xenopus laevis and mice, after complete spinal cord transection. Our results on both models demonstrated positive impacts of ASC secretome on their functional recovery which were correlated with histopathological markers of regeneration. Furthermore, in our mice study, secretome induced white matter preservation together with modulation of the local and peripheral inflammatory response. Altogether, these results demonstrate the neuroregenerative and potential for inflammatory modulation of ASC secretome suggesting it as a good candidate for cell-free therapeutic strategies for SCI.

Role Of PD-1 Immune Checkpoint Inhibition in Lung Cancer Treatment

Non-small cell lung cancer (NSCLC) can be distinguished by histopathology and tumor markers. The treatment methods of NSCLC mainly include radiotherapy, chemotherapy, surgical treatment and TCM therapy. PD-1/PD-L1 immunotherapy has an advantage in combination therapy, producing a low-toxic, long-acting antitumor immune response in cancer therapy. This thesis describes the main methods of NSCLC therapy, details the PD-1/PD-L1 pathway and immunotherapy, and studies applications of three monoclonal antibodies in monotherapy and combination therapy. We conclude that the combination therapy has the outstanding advantage of safety, mild effect and prediction, but the problem of drug resistance to PD-1/PD-L1 needs to be solved urgently.

Abstract C092: Genetic profiling of high grade serous ovarian cancer among women of African ancestry

Abstract (A) AN INTRODUCTORY SENTENCE INDICATING THE PURPOSES OF THE STUDY: Ovarian cancer (OC) is a heterogeneous disease with high grade serous ovarian cancer (HGSOC) as the commonest, the most aggressive tumor, which is often diagnosed at advanced stages, and with poor overall survival. Unfortunately, like many other cancer diagnoses, women of West African ancestry (Black women) with ovarian cancer experience worse outcomes than White women. In the US, Black women have higher morbidity and mortality rates and higher un-staged or unclassified tumors compared with White women, resulting in undertreatment with subsequent compromise in progression-free survival. Genomic instability is one of the most common underlying features of ovarian cancer and defective DNA damage repair has been implicated. The goal is to uncover canonical genes associated with the aggressive behavior of HGSOC in a cohort of black women that could explain the biology of this tumor. (B) A BRIEF DESCRIPTION OF PERTINENT EXPERIMENTAL PROCEDURES: Formalin fixed paraffin embedded (FFPE) HGSOC tissue blocks from Nigeria in West Africa (WAB), Bahama in Caribbean (CBB), and Miami in USA (USB) were identified and selected after rigorous review and confirmation with immunohistochemical (IHC) markers when needed. Integration of digital histopathology and IHC markers (estrogen receptor, progesterone receptor, Ki67 and P53), whole exome sequence, RNA sequence of the FFPE samples was used to identify the proportion of genomic instability and defective DNA damage repair genes. We use spatial genomic library on tissue microarray (TMA) slide prepared on GeoMx digital spatial profiler (DSP) Nanostring platform to study the biology of the tumor and the tumor microenvironment (TME) and proteogenomics.(C) A SUMMARY OF THE NEW, UNPUBLISHED DATA: The unsupervised principal component analysis of the tumor showed a distinct population of WAB and USB while the CBB showed admixture population. BACH2, ARG1, NAFT2 and FRA10A1 are commonly differentially expressed genes among the cohort. There is low expression of routine IHC markers among the WAB compared to the other groups. Conclusion: There is variation on gene expression by nativity and we hope to explore this variation for therapeutic purpose among black women with ovarian cancer. Citation Format: Ayodele Omotoso, Uchenna Ezenkwa, Raleigh Butler, Melissa Castillo, Alex Sanchez-Covarrubias, Matthew Schlumbrecht, Andre Pinto, Bala Audu, Sophia George. Genetic profiling of high grade serous ovarian cancer among women of African ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C092.

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Crusted scabies in a rabbit model: a severe skin disease or more?

BackgroundAround 200–300 million people are estimated to be affected by scabies annually worldwide. However, the mechanisms by which this disease may affect the general condition of the host are not entirely clear. The aim of the present study was to evaluate the systemic changes that may accompany crusted scabies in both treated and non-treated experimental animals.MethodsMale New Zealand rabbits were infected with Sarcoptes scabiei var. cuniculi and divided into the following three groups: control, ivermectin-treated, and fluralaner-treated. Several methods were used to evaluate the systemic changes, including histopathological examination of the liver, kidney, heart, and spleen, as well as the measurement of serum biochemical parameters and immunological parameters.ResultsSeveral definite structural and functional changes at the systemic level were revealed, as evidenced by the observed histopathological changes in the tissue sections of internal organs and the highly significant increases in markers of systemic inflammation, serum procalcitonin, and oxidative stress markers. Abnormalities in the liver and renal function results, as well as in the serum lipid profile, were also noted. Additionally, a disorganized immune response was noted, evidenced by a mixed type 1 and type 2 helper T cell response. Although there was notable clinical and parasitological cure in the ivermectin-treated group, the histopathological, biochemical, and immunological markers indicated incomplete resolution. In contrast, the fluralaner-treated group exhibited a nearly complete resolution of changes in these parameters.ConclusionsWe conclude that crusted scabies is a systemic syndrome that can affect several organs besides the skin. Inflammation, oxidative stress, and possibly bacterial infections, are all implicated as underlying mechanisms of tissue damage due to the disease. We recommend that fluralaner, a promising scabicidal agent, should be studied for possible human use, and especially for control programs.Graphical

Newly fabricated zinc oxide nanoparticles loaded materials for therapeutic nano delivery in experimental cryptosporidiosis

Cryptosporidiosis is a global health problem that threatens the lives of immunocompromised patients. This study targets to fabricate and investigate the efficiency of zinc oxide nanoparticles (ZnO-NPs), nitazoxanide (NTZ)-loaded ZnO-NPs, and Allium sativum (A. sativum)-loaded ZnO-NPs in treating cryptosporidiosis. Further FTIR, SEM, XRD, and zeta analysis were used for the characterization of ZnO-NPs and loaded materials. The morphology of loaded materials for ZnO-NPs changed into wrapped layers and well-distributed homogenous particles, which had a direct effect on the oocyst wall. The charge surface of all particles had a negative sign, which indicated well distribution into the parasite matrix. For anti-cryptosporidiosis efficiency, thirty immunosuppressed Cryptosporidium parvum-infected mice, classified into six groups, were sacrificed on the 21st day after infection with an evaluation of parasitological, histopathological, and oxidative markers. It was detected that the highest reduction percent of Cryptosporidium oocyst shedding was (81.5%) in NTZ, followed by (71.1%) in A. sativum-loaded ZnO-NPs-treated groups. Also, treatment with A. sativum and NTZ-loaded ZnO-NPs revealed remarkable amelioration of the intestinal, hepatic, and pulmonary histopathological lesions. Furthermore, they significantly produced an increase in GSH values and improved the changes in NO and MDA levels. In conclusion, this study is the first to report ZnO-NPs as an effective therapy for treating cryptosporidiosis, especially when combined with other treatments that enhance their antioxidant activity. It provides an economical and environment-friendly approach to novel delivery synthesis for antiparasitic applications.

Immunohistochemical markers predicting recurrence following resection and radiotherapy in chordoma patients: insights from a multicenter study [RETRACTED

Chordomas are rare tumors that often recur regardless of surgery with negative margins and postoperative radiotherapy. The predictive accuracy of widely used immunohistochemical (IHC) markers in addressing the recurrence of skull base chordomas (SBCs) is yet to be determined. This study aimed to investigate IHC markers in the prediction of recurrence after SBC resection with adjuvant radiation therapy. The authors reviewed the records of patients who had treatment for SBC between January 2017 and June 2021 across the Mayo Clinic in Minnesota, Florida, and Arizona. Exclusion criteria included patients who had no histopathology or recurrence as an outcome. Histopathological markers included cytokeratin A1/A3 only, epithelial membrane antigen (EMA), S100 protein, pan-cytokeratin, IN1, GATA3, CAM5.2, OSCAR, and chondroid. Information from patient records was abstracted, including treatment, clinical and radiological follow-up duration, demographics, and histopathological factors. Decision tree and random forest classifiers were trained and tested to predict the recurrence based on unseen data using an 80/20 split. A total of 38 patients with a diagnosis of SBC who underwent resection (gross-total resection: 42.1%; and subtotal resection: 57.9%) and radiation therapy were extracted from the medical records. The mean patient age was 48.2 (SD 19.6) years; most patients were male (n = 23; 60.5%) and White (n = 36; 94.7%). Pan-cytokeratin was associated with an increased risk of postoperative recurrence (OR 14.67, 95% CI 2.44-88.13; p = 0.00517) after resection and adjuvant radiotherapy. The decision tree analysis found pan-cytokeratin-positive tumors to have a 78% chance of being classified as a recurrence, with an accuracy of 75%. The distribution of minimal depth in the prediction of postoperative recurrence indicates that the most important variables were pan-cytokeratin, followed by cytokeratin A1/A3 and EMA. The authors' machine learning algorithm identified pan-cytokeratin as the largest contributor to recurrence among other IHC markers after SBC resection. Machine learning may facilitate the prediction of outcomes in rare tumors, such as chordomas.

Mesoscopic Assessment of Microstructure in Glioblastomas and Metastases by Merging Advanced Diffusion Imaging with Immunohistopathology.

Glioblastomas and metastases are the most common malignant intra-axial brain tumors in adults and can be difficult to distinguish on conventional MR imaging due to similar imaging features. We used advanced diffusion techniques and structural histopathology to distinguish these tumor entities on the basis of microstructural axonal and fibrillar signatures in the contrast-enhancing tumor component. Contrast-enhancing tumor components were analyzed in 22 glioblastomas and 21 brain metastases on 3T MR imaging using DTI-fractional anisotropy, neurite orientation dispersion and density imaging-orientation dispersion, and diffusion microstructural imaging-micro-fractional anisotropy. Available histopathologic specimens (10 glioblastomas and 9 metastases) were assessed for the presence of axonal structures and scored using 4-level scales for Bielschowsky staining (0: no axonal structures, 1: minimal axonal fragments preserved, 2: decreased axonal density, 3: no axonal loss) and glial fibrillary acid protein expression (0: no glial fibrillary acid protein positivity, 1: limited expression, 2: equivalent to surrounding parenchyma, 3: increased expression). When we compared glioblastomas and metastases, fractional anisotropy was significantly increased and orientation dispersion was decreased in glioblastomas (each P < .001), with a significant shift toward increased glial fibrillary acid protein and Bielschowsky scores. Positive associations of fractional anisotropy and negative associations of orientation dispersion with glial fibrillary acid protein and Bielschowsky scores were revealed, whereas no association between micro-fractional anisotropy with glial fibrillary acid protein and Bielschowsky scores was detected. Receiver operating characteristic curves revealed high predictive values of both fractional anisotropy (area under the curve = 0.8463) and orientation dispersion (area under the curve = 0.8398) regarding the presence of a glioblastoma. Diffusion imaging fractional anisotropy and orientation dispersion metrics correlated with histopathologic markers of directionality and may serve as imaging biomarkers in contrast-enhancing tumor components.

Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort.

Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research. The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study's prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks. The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage. This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

Demystifying Breast Disease Markers.

Breast imaging radiologists regularly perform image-guided biopsies of suspicious breast lesions based on features that are associated with a likelihood of malignancy ranging from 2% to greater than 95% (Breast Imaging Reporting and Data System categories 4 and 5). As diagnostic partners, pathologists perform histopathologic assessment of these tissue samples to confirm a diagnosis. Correlating the imaging findings with the histopathologic results is an integral aspect of multidisciplinary breast care. Assessment of radiologic-pathologic concordance is vital in guiding appropriate management, as it enables identification of discordant results, minimizing the chance of misdiagnosis. Undersampling can lead to false-negative results, with the frequencies of false-negative diagnoses varying on the basis of multiple factors, including biopsy type (eg, core needle, vacuum-assisted needle), needle gauge, and type of lesion sampled at biopsy (ie, mass, calcifications, asymmetry, architectural distortion). Improving a radiologist's knowledge of macroscopic and microscopic breast anatomy and more common breast diseases and their expected imaging findings ensures more accurate radiologic-pathologic correlation and management recommendations. The histopathologic and molecular characteristics of biopsy-sampled breast lesions aid in making an accurate diagnosis. Hematoxylin-eosin staining provides critical morphologic details, whereas immunohistochemical staining enables molecular characterization of many benign and malignant lesions, which is critical for tailored treatment. The authors review commonly encountered benign and malignant breast diseases, their corresponding histopathologic phenotypes, and the histopathologic markers that are essential to clinching the diagnosis of these entities. As part of a multidisciplinary team that provides optimal patient care, radiologists should be knowledgeable of the foundations of histopathologic diagnosis and the implications for patient management to ensure appropriate radiologic-pathologic concordance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

PD-L1 Expression in Pituitary Neuroendocrine Tumors/Pituitary Adenomas.

About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. PD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.

Usefulness of COL11A1 as a Prognostic Marker of Tumor Infiltration.

Determining the infiltration of carcinomas is essential for the proper follow-up and treatment of cancer patients. However, it continues to be a diagnostic challenge for pathologists in multiple types of tumors. In previous studies (carried out in surgical specimens), the protein COL11A1 has been postulated as an infiltration marker mainly expressed in the extracellular matrix (ECM). We hypothesized that a differential expression of COL11A1 may exist in the peritumoral stroma of tumors that have acquired infiltrating properties and that it may be detected in the small biopsies usually available in normal clinical practice. In our study, we performed immunohistochemical staining in more than 350 invasive and noninvasive small samples obtained via core needle biopsy (CNB), colonoscopy, or transurethral resection of bladder tumor (TURBT) of breast, colorectal, bladder, and ovarian cancer. Our results revealed that COL11A1 immunostaining had a sensitivity to classify the samples into infiltrative vs. noninfiltrative tumors of 94% (breast), 97% (colorectal), >90% (bladder), and 74% (ovarian); and a specificity of 97% (breast), 100% (colorectal), and >90% (bladder). In ovarian cancer, the negative predictive value (0.59) did not present improvement over the usual histopathological markers. In all samples tested, the cumulative sensitivity was 86% and the specificity 96% (p < 0.0001). COL11A1-positive immunostaining in small biopsies of breast, colon, bladder and ovarian cancer is an accurate predictive marker of tumor infiltration that can be easily implemented in daily clinical practice.

Diabetes exacerbates inflammatory bowel disease in mice with diet-induced obesity.

The increased prevalence of inflammatory bowel disease (IBD) among patients with obesity and type 2 diabetes suggests a causal link between these diseases, potentially involving the effect of hyperglycemia to disrupt intestinal barrier integrity. To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced obesity. Mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range hyperglycemia. Six weeks later, dextran sodium sulfate was given to induce colitis. In select experiments, a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis onset. Endpoints included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier integrity. In mice given a high-fat diet, but not chow-fed animals, diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease severity. Diabetes was also associated with a decrease in key components that regulate colonic epithelial barrier integrity (colonic mucin layer content and epithelial tight junction proteins) in diet-induced obese mice. Each of these effects of diabetes in diet-induced obese mice was ameliorated by restoring normoglycemia. In obese mice, diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of hyperglycemia. Hyperglycemia-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis severity. These findings suggest that effective diabetes management may decrease the clinical severity of IBD.

Biomarkers for Kidney-Transplant Rejection: A Short Review Study.

Kidney transplantation is the preferred treatment for end-stage renal failure, but the limited availability of donors and the risk of immune rejection pose significant challenges. Early detection of acute renal rejection is a critical step to increasing the lifespan of the transplanted kidney. Investigating the clinical, genetic, and histopathological markers correlated to acute renal rejection, as well as finding noninvasive markers for early detection, is urgently needed. It is also crucial to identify which markers are associated with different types of acute renal rejection to manage treatment effectively. This short review summarizes recent studies that investigated various markers, including genomics, histopathology, and clinical markers, to differentiate between different types of acute kidney rejection. Our review identifies the markers that can aid in the early detection of acute renal rejection, potentially leading to better treatment and prognosis for renal-transplant patients.

Ultrastructural Evidence of Eosinophil Clustering and ETosis in Association with Damage to Single Tumour Cells in a Case of Poorly Cohesive NOS Gastric Carcinoma.

A recent meta-analysis reported that TATE is a histopathological marker of favourable prognosis, particularly in patients with gastrointestinal cancer.Experimental studies have shown that eosinophils may exert antitumour activity through discharge of their highly cytotoxic granular proteins.Our ultrastructural findings add novel mechanism insights for eosinophil antitumoural activity, providing morphologic evidence of eosinophil ETosis in association with single tumour cell injury.