Laboratory Investigation; a Journal of Technical Methods and Pathology

Digital pathology has transformed the traditional pathology practice of analyzing tissue under a microscope into a computer vision workflow. Whole slide imaging allows pathologists to view and analyze microscopic images on a computer monitor, enabling computational pathology. By leveraging artificial intelligence (AI) and machine learning (ML), computational pathology has emerged as a promising field in recent years. Recently, task-specific AI/ML (e.g., convolutional neural networks) has risen to the forefront, achieving above-human performance in many image processing and computer vision tasks...

Epithelial ovarian cancer (EOC) remains a significant cause of mortality among gynecological cancers, with the majority of cases being diagnosed at an advanced stage. Before targeted therapies were available, EOC treatment relied largely on debulking surgery and platinum-based chemotherapy. Vascular endothelial growth factors (VEGFs) have been identified as inducing tumor angiogenesis. According to several clinical trials, anti-VEGF targeted therapy with bevacizumab was effective in all phases of EOC treatment...

Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical grade digital pathology adoption and patient safety. In this work, we describe the development of a structured digital pathology laboratory quality management system (QMS) for the clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK)...

Pathology laboratories are increasingly using digital workflows. This has the potential of increasing lab efficiency, but the digitization process also involves major challenges. Several reports have been published describing the individual experiences of specific laboratories with the digitization process. However, a comprehensive overview of the lessons learned is still lacking. We provide an overview of the lessons learned for different aspects of the digitization process, including digital case management, digital slide reading, and computer-aided slide reading...

BAG-1L (BCL-2-associated athanogene-1L) is a critical co-regulator that binds to and transactivates the androgen receptor (AR), leading to prostate cancer development and progression. Studies investigating the clinical importance of BAG-1L protein expression in advanced prostate cancer have been limited by the paucity of antibodies that specifically recognize the long isoform. In this study, we have developed and validated a new BAG-1L specific antibody using multiple orthogonal methods across several cell lines with and without genomic manipulation of BAG-1L and all BAG-1 isoforms...

Renal amyloidosis is a rare condition caused by the progressive accumulation of misfolded proteins within glomeruli, vessels and interstitium, causing functional decline and requiring prompt treatment due to its significant morbidity and mortality. Congo Red (CR) stain on renal biopsy is the gold standard for the diagnosis, but the need for polarized light is limiting the digitization of this nephropathology field. This study explores the feasibility and reliability of CR fluorescence on virtual slide (CRFvs) evaluating the diagnostic accuracy and proposing an automated digital pipeline for its assessment...

Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio HPV 23 genotyping results and immediate cervical histologic diagnosis (within 6 months after HPV genotyping), between November 2015 and October 2022...

We examined the effects of gene ablation and chemical inhibition of transient receptor potential ankyrin 1 (TRPA1) on the growth of experimental argon laser-induced choroidal neovascularization (CNV) in mice. CNV was induced in the eyes of 6 - 8-week-old mice by argon laser irradiation and observed expression. This reaction was compared between TRPA1-null (KO) mice and wild-type (WT) mice. Gene expression analysis was performed in laser-injured tissues on day 1 and 3. CNV growth was evaluated on day 14. Finally, reciprocal bone marrow transplantation was performed between each genotype of mice to identify the responsible components of either recipient tissue or bone marrow-derived inflammatory cells...

Alveolar capillary dysplasia with misalignment of pulmonary Veins (ACDMPV) is a lethal congenital lung disorder that presents shortly after birth with respiratory failure and therapy-resistant pulmonary hypertension. It is associated with heterozygous point mutations and genomic deletions that involve the FOXF1 gene or its upstream regulatory region. Patients are unresponsive to the intensive treatment regiments and suffer unnecessarily, because ACDMPV is not always timely recognized and histological diagnosis is invasive and time-consuming...

Animal models of cirrhosis are of great interest to investigate the pathological process leading to the final stage of cirrhosis. The aim of this study was to analyze the different steps involved in the progressive development of cirrhosis using Fourier transform infrared spectral histology in 2 mouse models of cirrhosis, the STAM model of metabolic cirrhosis, and the carbon tetrachloride-induced cirrhosis model. Formalin-fixed, paraffin-embedded liver samples were obtained from 3 mice at 5 time points in each model to analyze the course of hepatic lesions up to the formation of cirrhosis...

Wnt signaling plays a crucial role in the progression of various cancers, including oral squamous cell carcinoma (OSCC). However, the tumor microenvironment (TME) regulating Wnt signaling has not yet been fully elucidated. In this study, we investigated whether cancer-associated fibroblasts (CAFs), the primary components of the TME, activate Wnt signaling and promote tumor progression in OSCC. We conducted a Transwell coculture assay using human OSCC cell lines and normal human dermal fibroblasts (NHDFs). NHDFs stimulated WNT7A expression in several OSCC cell lines, especially HO-1-N-1 and HSC-5...

Acute kidney injury (AKI) is a complex clinical syndrome with a rapid decrease in renal function caused by several different etiologies, including sepsis, ischemia, and the administration of nephrotoxic drugs. Tubular arginase 2 (ARG2), an arginine-metabolic enzyme, is a potential therapeutic target for AKI, but it has not been confirmed under various AKI conditions. The aim of this study was to investigate ARG2 as a therapeutic target for cisplatin-induced AKI. Cisplatin-treated mice with a genetic deficiency in Arg2 had a significant amelioration of renal dysfunction, characterized by decreased acute tubular damage and apoptosis...

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then KLF5 was knocked down in HLECs to explore its function roles and underlying mechanisms...

Rapid and accurate cytomegalovirus (CMV) identification in immunosuppressed or immunocompromised patients presenting with diarrhea is essential for therapeutic management. Due to viral latency, however, the gold standard for CMV diagnosis remains to identify viral cytopathic inclusions on routine hematoxylin and eosin (H&E) stained tissue sections. Therefore, biopsies may be taken and "rushed" for pathology evaluation. Here we propose the use of artificial intelligence (AI) to detect CMV inclusions on routine H&E stained whole slide images (WSIs) to aid pathologists in evaluating these cases...

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common causes of chronic liver disease worldwide, and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy (MPM), based on the second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), was used to label-free image the samples of non-alcoholic fatty liver...

In an anatomic pathology laboratory, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to characterize amyloid deposits identified in formalin-fixed, paraffin-embedded tissue (FFPET). However, the development of additional tests is partially limited by the lack of information the passage of time has on the proteins in FFPET. To investigate the reliability of LC-MS/MS in the analysis of old FFPET specimens, one bone marrow aspirate clot was analyzed by LC-MS/MS yearly from 2014-2018, in 3 consecutive months...

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder (OPMD) associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications...

Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40, and negative for s100 and αSMA, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of six cases of HCCC including two atypical subtypes-a case of "high-grade transformation" and one with "possessing a novel partner gene for EWSR1...

Pathological histology is the gold standard for clinical diagnosis of cancer. Incomplete or excessive sampling of the formalin-fixed excised cancer specimen will result in inaccurate histological assessment or excessive workload. Conventionally, pathologists perform specimen sampling relying on naked-eye observation, which is subjective and limited by human perception. Precise identification of cancer tissue, size, and margin is challenging, especially for lesions with inconspicuous tumor. To break the limits of human eye perception (visible: 400-700 nm) and improve the sampling efficiency, in this study, we propose using a second near-infrared window (NIR-II: 900-1700 nm) hyperspectral imaging (HSI) system to assist specimen sampling on the strength of the verified deep anatomical penetration and low scattering characteristics of the NIR-II optical window...

Pheochromocytoma/paraganglioma (PPGL) is an endocrine-related tumor associated with excessive catecholamine release and has limited treatment options once metastasis occurs. Although recent phase II clinical trials of immune checkpoint inhibitors in the treatment of PPGL have preliminarily shown promising results, the fundamentals of immunotherapy for PPGL have not yet been established. In the early research, using bulk RNA sequencing of tumor samples from seven PPGL patients, we found that PPGL tumor tissues exhibited high PD-L1 mRNA expression compared with adjacent normal adrenal medulla tissues, and this was related to T cell exhaustion biomarkers...