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mTOR Pathway Activation Assessed by Immunohistochemistry in Cervical Biopsies of HPV-associated Endocervical Adenocarcinomas (HPVA): Correlation With Silva Invasion Patterns
The Silva pattern of invasion, recently introduced to stratify patients at risk for lymph node metastases in human papillomavirus-associated endocervical adenocarcinomas (HPVAs), can only be assessed in cone and loop electrosurgical excision procedure excisions with negative margins or in a hysterectomy specimen. Previous studies found associations between destructive stromal invasion patterns (Silva patterns B and C) and mutations in genes involved in the MEK/PI3K pathways that activate the mammalian target of rapamycin (mTOR) pathway. The primary aim of this study was to use cervical biopsies to determine whether markers...
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

GPBAR1 Promotes Proliferation of Serous Ovarian Cancer by Inducing Smad4 Ubiquitination
Conclusions: GPBAR1 was overexpressed in SOC and predicted the poor prognosis of SOC. We showed that GPBAR1 promoted SOC proliferation by activating ERK and ubiquitining Smad4. Our results suggested that GPBAR1 was a supplement to better classify SOC on the basis of the molecular profile and that GPBAR1 may be a potential drug target of SOC. (Source: Applied Immunohistochemistry and Molecular Morphology)
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Increased PA2G4 Expression Is an Unfavorable Factor in Nasopharyngeal Carcinoma
PA2G4 plays a dual role in tumors. However, the correlation of its expression with clinical feature and prognosis has never been reported in nasopharyngeal carcinoma (NPC). Using immunohistochemical staining, we examined PA2G4 protein level in clinicopathologically characterized 201 NPC cases (138 male and 63 female) with age ranging from 21 to 83 years and 45 nasopharyngeal (NP) tissues. Statistical methods were used to assess the difference in PA2G4 expression and its relationship with clinical parameters and prognosis in NPC. Immunohistochemical analysis showed that the protein expression of PA2G4 examined in NPC tissue...
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Digital Imaging Analysis Reveals Reduced Alveolar α-Smooth Muscle Actin Expression in Severe Asthma
The objective of this study was to evaluate α-SMA expression in the alveolated parenchyma of individuals with severe asthma (SA), compared with healthy controls or individuals with chronic obstructive pulmonary disease. Using quantitative digital image analysis and video-assisted thoracoscopic surgery lung biopsies, we show that alveolated parenchyma α-SMA expression is markedly reduced in SA in comparison to healthy controls (mean %positive pixels: 12% vs. 23%, P=0.005). Chronic obstructive pulmonary disease cases showed a similar, but trending, decrease in α-SMA positivity compared with controls (mean %positivity: 17%...
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Digital Image Analysis of the Proliferation Markers Ki67 and Phosphohistone H3 in Gastroenteropancreatic Neuroendocrine Neoplasms: Accuracy of Grading Compared With Routine Manual Hot Spot Evaluation of the Ki67 Index
This study aimed to evaluate digital image analysis (DIA) as an objective assessment of proliferation markers in GEP-NENs. A consecutive cohort of patients with automated DIA measurement of Ki67 (DIA Ki67) and phosphohistone H3 (DIA PHH3) on immunohistochemical slides was analyzed using Visiopharm image analysis software (Hoersholm, Denmark). The results were compared with the Ki67 index from routine pathology reports (pathology Ki67). The study included 159 patients (57% males). The median pathology Ki67 was 2.0% and DIA Ki67 was 4.1%. The interclass correlation coefficient of the DIA Ki67 compared with the pathology Ki67...
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Digital Pathology Slides-based Measurement of Tumor Cells and Lymphocytes Within Cytology Samples Supports the Relevance of the Separation by Size of Nonhematological Tumor and Hematological Nontumor Cells in Liquid Biopsies
Filtration by size is one method used to study circulating tumor cells in blood samples. Filtration-migration ability is highly dependent of the size of cell nucleus. This implies to search for the appropriate nucleus size able to separate between hematological nucleated and nonhematological nucleated blood cells to maximize circulating tumor cell isolation. Digitalized cytology slides [May-Grünwald Giemsa (MGG) stained and immunocytochemistry (ICC) slides] from various cancer metastases served for manual measurements of nuclei about tumor cells and adjacent lymphocytes to determine the diameters the more able to separate...
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Technical Article Source Type: research

Quantitative Image Analysis for Tissue Biomarker Use: A White Paper From the Digital Pathology Association
Tissue biomarkers have been of increasing utility for scientific research, diagnosing disease, and treatment response prediction. There has been a steady shift away from qualitative assessment toward providing more quantitative scores for these biomarkers. The application of quantitative image analysis has thus become an indispensable tool for in-depth tissue biomarker interrogation in these contexts. This white paper reviews current technologies being employed for quantitative image analysis, their application and pitfalls, regulatory framework demands, and guidelines established for promoting their safe adoption in clini...
Source: Applied Immunohistochemistry and Molecular Morphology - August 1, 2021 Category: Chemistry Tags: Review Article Source Type: research

Immunostaining for NeuN Does Not Show all Mature and Healthy Neurons in the Human and Pig Brain: Focus on the Hippocampus
We report on the techniques and results used to enhance the staining for NeuN in that tissue. In parallel, we stained NeuN in piglet brain tissue, sourced from an experimental model where methodological parameters, including those for tissue fixation and storage, were tightly controlled. In human FFPE brain tissue, we were unable to enhance NeuN immunostaining to a degree sufficient for cell counting. In contrast, we found consistently high levels of staining in the piglet brain tissue. We conclude that processes used for fixation and storage of human FFPE brain tissue are responsible for the reduced staining. These result...
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Online Article: Research Article Source Type: research

Optimization of Mouse-on-Mouse Immunohistochemistry by Utilizing Fluorescent-dye Conjugated Secondary Anti-Mouse Antibody
In this study, we provide evidence showing the potential of the fluorescent-dye conjugated secondary anti-mouse antibody for reducing the background noise in the mouse-on-mouse immunohistochemistry. Furthermore, our findings demonstrate the inadequacy of goat serum/protein-blocking solution alone as an immunohistochemistry blocking system for reducing the background noise. (Source: Applied Immunohistochemistry and Molecular Morphology)
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Technical Article Source Type: research

A Retrospective Study and Literature Review of Cervical Villoglandular Adenocarcinoma: A Candidate Paradigm of Silva System Pattern A
In conclusion, VGA is a rare subtype of adenocarcinoma of the uterine cervix with distinct exophytic, villous-papillary growth pattern and extremely excellent prognosis, which corresponds with pattern A in Silva system, while its underlying mechanism and genetic background is still far from well known. (Source: Applied Immunohistochemistry and Molecular Morphology)
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

PD-L1 Expression Harmonization in Gastric Cancer Using 22C3 PharmDx and SP263 Assays
The immune checkpoint inhibitor Pembrolizumab has been FDA-approved for the treatment of gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in patients who fail second-line therapy and test positive by a companion programed death ligand 1 (PD-L1) assay, the 22C3 PharmDx. It would be useful to investigate the potential interchangeability of other PD-L1 assays in order to develop a more sustainable diagnostic strategy. We investigated the possibility of harmonizing different PD-L1 assays, utilizing samples from 94 GC and GEJ patients to compare their expression using 2 laboratory developed tests (LDTs): The Dako ...
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Immunohistochemical Staining With Neuroendocrine Markers is Essential in the Diagnosis of Neuroendocrine Neoplasms of the Esophagogastric Junction
In conclusion, immunohistochemical staining with neuroendocrine markers is essential for the diagnosis of NENs, and to detect all NENs, we recommend to perform this routinely on all resected tumors of the EGJ. (Source: Applied Immunohistochemistry and Molecular Morphology)
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Immunohistochemical Examination is Highly Sensitive and Specific for Detection of the V600E BRAF Mutation in Colorectal Serrated Lesions
Mutations in BRAF are important events in colorectal serrated lesions and specific genetic markers for the serrated pathway. However, examination of BRAF mutations is not easy in routine histopathologic analyses. Here, the authors examined 73 colorectal serrated lesions, including 21 hyperplastic polyps, 32 traditional serrated adenomas, and 30 sessile serrated lesions, for comparison of BRAF mutation status with immunopositive expression of the anti-BRAF V600E mutation-specific antibody VE1. Thirty-two tubular adenomas (TAs) were examined as controls. In addition, 5 examples of sessile serrated lesion with dysplasia were ...
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Positive MITF and NKI/C3 Expression in Cellular Neurothekeoma and Dermatofibroma
Conclusion: CNT and DF share demographic, histopathologic, and immunohistochemical features, including shared expression of MITF and NKI/C3, especially cellular DF. (Source: Applied Immunohistochemistry and Molecular Morphology)
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research

Hybrid Schwannoma/Perineurioma: Morphologic Variations and Genetic Profiles
To clarify the morphologic spectrum and molecular profiles of hybrid schwannoma/perineurioma (HSP), we investigated 15 tumors clinicopathologically and cytogenetically. HSP was classified into 2 morphologic types: mixed cellular and combined tumor types. The former comprising of 14 tumors mostly arose in the subcutaneous tissue of the extremities and the trunk of middle-aged adults. They were well-circumscribed and composed of elongated spindle-shaped tumor cells arranged in storiform and whorl patterns. Immunostaining revealed a mixed cellular proliferation of S-100 protein-positive and SOX10-positive Schwann cells and ep...
Source: Applied Immunohistochemistry and Molecular Morphology - July 1, 2021 Category: Chemistry Tags: Research Articles Source Type: research