Applied immunohistochemistry & molecular morphology : AIMM最新文献

{"title":"The Application of RNAscope Protocol to Detect Dengue Virus in Human Paraffin-Embedded Tissue.","authors":"Carla Pagliari, Geovanna M Marcoli, Luciane K Galo, Aline K Assato, Leda V de Carvalho, Ricardo Penny, Evandro S de Mello, Mirian N Sotto","doi":"10.1097/PAI.0000000000001355","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001355","url":null,"abstract":"<p><p>Dengue is an important arthropod-borne viral disease, endemic in over 100 countries and challenging health care systems worldwide São Paulo, Brasil. The disease can be clinically diagnosed by the detection of dengue-specific antibodies, nonstructural 1 antigen, or viral RNA by reverse transcriptase-polymerase chain reaction São Paulo, Brasil. When there is an indication to perform a biopsy or in cases of retrospective studies using material from necropsy, immunohistochemistry is an efficient tool. Recently, RNAscope has emerged as a new generation of in situ hybridization technique, with the advantage of different probes, including a probe to Dengue virus. This paper aimed to analyze the use of the RNAscope technique as a supplementary method, compared to immunohistochemistry, for the evaluation of dengue virus in human specimens. An immunohistochemical and molecular study was conducted in pulmonary and renal tissues from individuals who died due to severe dengue, selected according to clinical and serological diagnosis. The immunohistochemical assay was performed using a monoclonal anti-dengue virus antibody. Positivity was visualized in the cytoplasm of mononuclear cells in the interalveolar septal region and also in glomeruli and tubules. RNAscope was performed using a probe to dengue type 2. It was possible to visualize the positivity as small dots or clusters in the same area in the lungs and tubules in the kidney specimen. The finding of dots or clusters through the RNAscope protocol could suggest viral replication; however, only the finding of replicative intermediates or cultures would confirm such activity.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological and Prognostic Value of Neutrophil-Lymphocyte Infiltration in Oral Squamous Cell Carcinoma.","authors":"Andressa F P Miguel, Nicole Lonni, Túlio S Rosa, Daniella S C Vieira, Filipe Modolo, Elena R C Rivero","doi":"10.1097/PAI.0000000000001357","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001357","url":null,"abstract":"<p><p>This study aims to explore the influence of CD66b+ and CD8+ tumor infiltration, along with the tumoral neutrophil-lymphocyte ratio (tNLR) and blood neutrophil-lymphocyte ratio (bNLR), on the clinicopathological features and prognosis of oral squamous cell carcinoma (OSCC) patients. Clinicopathological parameters and survival data were retrospectively collected from 46 patients with OSCC. bNLR was determined using a complete blood count test. tNLR was assessed by counting immunostained cells for CD66b (neutrophils) and CD8 (cytotoxic T cells) across different tumor regions (tumor center and invasive front) and compartments (parenchyma and stroma). Prognostic impacts on overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier survival curves. Smoking history correlated with higher bNLR. Blood lymphocyte counts were significantly higher in surviving patients (P=0.014). TNM stage I/II tumors exhibited better OS and lower CD66b+ cell counts compared to stage III/IV. Increased CD66b+ counts (P<0.034), higher stromal CD8+ counts, and tNLR above the median were linked to worse OS. Furthermore, elevated stromal CD8+ counts at the invasive front were associated with significantly lower PFS (P=0.038). In conclusion, CD8+, CD66b+, and NLR were associated with poorer survival outcomes in OSCC, suggesting their potential as therapeutic targets and improved prognostic models.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Frequency of CSF1R Expression in Histiocytosis.","authors":"Jean-François Emile, Lévi-Dan Azoulay, Sébastien Héritier, Fleur Cohen-Aubart, Zofia Hélias-Rodzewicz, Irena Antona Ungureanu, Jean Donadieu, Julien Haroche","doi":"10.1097/PAI.0000000000001359","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001359","url":null,"abstract":"","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine Differentiation in Synovial Sarcoma-An Immunohistochemical Study of 357 Tumors With 4 Markers: Chromogranin A, Synaptophysin, Insulinoma-associated Protein 1 and Insulin Gene Enhancer Protein ISL-1.","authors":"Maria Del Carmen Rodriguez Pena, Niharika Shah, Mayank Patel, Maciej Kaczorowski, Małgorzata Chłopek, Anna Jasiak, Natálie Klubíčková, Kris Ylaya, Janusz Ryś, Michal Michal, Jerzy Lasota, Markku Miettinen","doi":"10.1097/PAI.0000000000001353","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001353","url":null,"abstract":"<p><p>Expression of neuroendocrine differentiation (NE) markers in synovial sarcoma may result in misdiagnosis as a neuroendocrine tumor. This investigation evaluated 357 synovial sarcomas to determine the presence of NE markers-chromogranin A (CgA), synaptophysin (SYP), insulinoma-associated protein 1 (INSM1), and insulin gene enhancer protein ISL-1 (ISLET1)-using immunohistochemistry. The cohort included 248 primary tumors, 28 metastases, 4 recurrences, and 77 undetermined lesions. The female-to-male ratio was equal (128/124), and patient ages ranged from 7 to 80 years (median=32). Lower (n=107) and upper (n=50) limbs represented the most frequent sites for primary tumors, while the lung (n=18) was the main site of metastasis. Tumors were classified as monophasic (n=289), biphasic (n=57), and poorly differentiated (n=11). Immunostainings were categorized as diffuse, patchy (≥10% and <75%), or focal (<10%). A diffuse staining pattern for SYP, INSM1, and ISLET1 was observed in 30 (8.4%), 1, and 3 tumors, respectively. Likewise, patchy immunoreactivity was detected in 30, 2, and 7 (2%) cases. In 2 tumors, only patchy CgA staining was noted. Strong, moderate-to-strong, moderate, and weak-to-moderate immunoreactivity for CgA, SYP, INSM1, and ISLET1 was observed in 1.4%, 18%, 2%, and 4% of cases, respectively. Nine tumors (2.5%) co-expressed 2 (n=6) or 3 markers. NE proteins were more commonly expressed in biphasic (~70%) than monophasic (~16%) tumors; the difference was statistically significant. One of 11 (9%) poorly differentiated synovial sarcomas showed ISLET1 immunoreactivity. Also, SSX2-fusion compared with SSX1-fusion tumors more frequently expressed NE markers (56.7% vs. 31.7%), but the difference was not statistically significant. In summary, the presence of NE differentiation proteins in certain synovial sarcomas can make diagnosis more difficult, particularly when assessing small biopsy samples where synovial sarcoma is not initially included in the differential diagnosis.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Algorithmic Approach to Diagnosis of Salivary Gland Neoplasms Based on Morphology and Select Immunostains.","authors":"Kathleen E Higgins, Nicole A Cipriani","doi":"10.1097/PAI.0000000000001350","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001350","url":null,"abstract":"<p><p>Salivary gland tumors present diagnostic challenges even to the experienced surgical pathologist due to overlap in both histologic and immunohistochemical features. Morphology, immunoprofile, and genetic testing (in some cases) can be used judiciously in an algorithmic approach to narrow the differential diagnosis on a salivary biopsy or resection specimen. The purpose of this review is to present an objective algorithmic approach to assessing salivary gland specimens that utilizes histomorphology, a limited panel of immunohistochemical stains, and, occasionally, genetics to aid in diagnosis. The diagnostic groups include: biphasic neoplasms, monophasic glandular neoplasms, monophasic squamoid neoplasms, and oncocytic neoplasms. This review is not exhaustive but covers the most frequently encountered and clinically relevant neoplasms. The suggested initial immunopanel for most tumors includes p40, CD117, and S100, with second-round immunostains depending on the specific differential diagnosis (beta-catenin, mammaglobin, DOG1, etc). One risks getting caught in the weeds of ever-expanding salivary neoplasia, and it is important to remember that, in order for clinicians to make treatment decisions, a specific diagnosis is not always required. Important information includes whether a tumor is low-grade (including benign), high-grade, possibly adenoid cystic, or eligible for targeted therapy. If possible, correlation of salivary biopsies to their ultimate resection specimen will help ensure diagnostic accuracy and promote active learning.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling NFκB and VEGF Expression in Mouse Embryonic Stem Cells, Lung Cancer Cells, and Fibroblasts.","authors":"Berrin Ozdil, Eda Acikgoz, Gulperi Oktem, Kubilay Dogan Kilic, Huseyin Aktug","doi":"10.1097/PAI.0000000000001347","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001347","url":null,"abstract":"<p><p>Cancer is one of the leading causes of morbidity and mortality worldwide, with lung cancer ranked among the most lethal malignancies. A key hallmark of cancer progression is neovascularization, primarily mediated by vascular endothelial growth factor (VEGF), which stimulates vasculogenesis and angiogenesis. In parallel, the transcription factor nuclear factor of kappa B (NFκB) plays a critical role in inflammation, immune regulation, and tumor development by modifying numerous signaling pathways. In this study, we aimed to compare the expression levels of VEGF and NFκB in mouse embryonic stem cells (mESCs), fibroblasts, and lung cancer cells (LCCs) to probe cell-type-specific regulatory profiles. Protein levels were evaluated using immunofluorescence staining and quantified by corrected total cell fluorescence (CTCF), while mRNA expression was analyzed to relate protein-level findings. Our results showed no significant difference in NFκB protein expression among the 3-cell types. In contrast, VEGF protein expression was significantly higher in fibroblasts and lung cancer cells compared with embryonic stem cells. These findings propose that while NFκB may play a stable regulatory role across cell types, VEGF exhibits a dynamic expression pattern linked with angiogenic potential and cellular differentiation status.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISIMM Page.","authors":"","doi":"10.1097/PAI.0000000000001354","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001354","url":null,"abstract":"","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":"34 5","pages":"361"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Klotho and LRP6 as Emerging Biomarkers in Gastric Adenocarcinoma: Expression Patterns and Clinical Relevance.","authors":"Marina B Youssef, Fatma A M Badary, Rabab M M Farghaly, Asmaa A Abdeltawab, Marwa T Hussien","doi":"10.1097/PAI.0000000000001293","DOIUrl":"10.1097/PAI.0000000000001293","url":null,"abstract":"<p><p>Gastric cancer (GC) is often diagnosed at an advanced stage, limiting treatment options and leading to poor outcomes. Klotho, a transmembrane anti-aging protein, generally functions as a tumor suppressor, while low-density lipoprotein receptor-related protein 6 (LRP6), a member of the low-density lipoprotein receptor family, is frequently overexpressed in various cancers. Klotho and LRP6 proteins are emerging regulators of Wnt/β-catenin signaling with potential roles in tumor biology. This retrospective study aimed to assess the prognostic significance of Klotho and LRP6 expression in gastric adenocarcinoma (GAC). Immunohistochemical analysis was conducted on tumor samples from 73 GAC patients. Low Klotho expression was significantly associated with younger age at diagnosis ( P =0.006), poorly cohesive carcinoma (PCC) and mucinous adenocarcinoma (MAC) variants ( P <0.001), diffuse type according to Lauren classification ( P =0.001), high-grade tumors ( P <0.001), lymph node (L.N) metastasis ( P =0.038), and distant metastases ( P =0.010), and advanced TNM stage ( P =0.033). High LRP6 expression was significantly correlated with diffuse type ( P =0.023), distant metastasis ( P =0.011), and advanced TNM staging ( P =0.046). Both low Klotho and high LRP6 expressions were associated with reduced overall survival (OS). Multivariate analysis identified high LRP6 expression as an independent predictor of poor OS and progression-free survival (PFS). In conclusion, low Klotho-high LRP6 expression was associated with poor OS, supporting its role as a prognostic biomarker and potential therapeutic target. Validation in larger patient cohorts is warranted to confirm their clinical utility.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"330-337"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Golgi-Pattern PDGFRA Immunoreactivity Correlates With PDGFRA Mutation Status in Gastric Epithelioid and Mixed-Type Gastrointestinal Stromal Tumors.","authors":"Rola H Ali, Maram Alwazan, Smiley George, Ahmad R Alsaber, Mohammad Alkandari","doi":"10.1097/PAI.0000000000001342","DOIUrl":"10.1097/PAI.0000000000001342","url":null,"abstract":"<p><p>Gastrointestinal stromal tumors (GISTs) with PDGFRA mutations represent a distinct subset with characteristic clinicopathological features and important therapeutic implications. The diagnostic performance of PDGFRA immunohistochemistry (IHC) as a phenotypic correlate of PDGFRA mutation status requires further evaluation. This study aimed to assess the diagnostic performance and reproducibility of PDGFRA IHC against PDGFRA mutation status as the reference standard. A total of 117 tumors were analyzed (19 PDGFRA -mutant, 40 non- PDGFRA , 49 GISTs of undetermined genotype, 9 non-GIST mimics). IHC for KIT, DOG1, CD34, and PDGFRA was performed on full sections and tissue microarrays, and 3 pathologists independently scored intensity, extent, and Golgi-pattern accentuation. PDGFRA -mutant GISTs were predominantly gastric with epithelioid or mixed morphology. Sixteen carried D842V, whereas 3 had exon 18 deletion or exon 12 mutations. KIT expression was reduced (47.4%) compared with non- PDGFRA -mutant GISTs (85%), while DOG1 remained consistently positive. Overall, PDGFRA expression was observed in 94.7% of PDGFRA -mutants compared with 32.5% of non- PDGFRA -mutants ( P< 0.001), and Golgi-pattern accentuation was present in 89.5% (17/19) of PDGFRA -mutants versus 7.5% (3/40) of molecularly confirmed non- PDGFRA -mutants ( P <0.001). Among non-GIST mimics, only a monophasic synovial sarcoma showed diffuse PDGFRA positivity. Interobserver agreement for PDGFRA was substantial (κ=0.691). PDGFRA IHC showed 95% sensitivity and 78% specificity but did not distinguish D842V from non-D842V variants. PDGFRA IHC correlates with PDGFRA -mutant genotype when diffuse Golgi-type staining is observed in a gastric epithelioid or mixed tumor showing reduced KIT expression. However, therapeutic selection-particularly for avapritinib-requires precise detection of D842V variants, which mandates molecular sequencing.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"295-303"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Evaluation of APAFIX and 10% Formalin for Human Histologic Tissue Preservation: A Pilot Study.","authors":"Nidal A Qinna, Husam A Abu-Farsakh, Bayan Y Ghanim, Ghayda' AlDabet, Jonathan Earl, Yasmine Mansouri, Sharib S Muhammad, Qurat-Ul-Ain Siddiqui, Muhammad A Naseer, Mehwish Mushtaq","doi":"10.1097/PAI.0000000000001337","DOIUrl":"10.1097/PAI.0000000000001337","url":null,"abstract":"<p><p>Formalin has long served as the standard fixative in histopathology; however, its limitations-such as antigen masking, nucleic acid degradation, and carcinogenicity-have prompted the search for safer alternatives. APAFIX, a formalin-free fixative, was developed to maintain diagnostic integrity while improving safety in routine tissue handling. This pilot study was conducted to compare the efficiency of the APAFIX solution with formalin in preserving human histologic tissue architecture and cellular morphology as assessed by routine Hematoxylin and Eosin (H and E) staining. Ten human biopsies from different tissue origins underwent standard H and E staining using the routine paraffin technique after 6 to 8 hours of postfixation in either APAFIX or 10% formalin. A blinded pathology review evaluated key histologic parameters, nuclear detail, lymphocyte visualization, fibrous tissue integrity, and overall tissue architecture, using a 10-point scoring system. Results revealed that APAFIX fixing solution was as effective as formalin fixation in terms of tissue quality during processing and sectioning, and in preserving architectural and cellular morphology. APAFIX solution showed enhanced nuclear detail and lymphocyte visualization with occasional fixation artifacts, such as pseudolipomatosis, observed in epithelial tissue. Formalin was more effective in preserving fibrous and epithelial areas. Overall, APAFIX demonstrated sufficient diagnostic performance across the studied pathologic biopsies. APAFIX is a promising formalin-free alternative for histologic tissue fixation, offering enhanced preservation of critical cellular features and eliminating health hazards associated with formalin. Further large-scale studies are warranted to validate its application across broader diagnostic settings and specialized staining techniques.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"354-360"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}