Maria Luiza Diniz de Sousa Lopes, Débora Frota Colares, Tiago João da Silva Filho, Laura Priscila Barboza de Carvalho, Lélia Batista de Souza, Éricka Janine Dantas da Silveira
{"title":"Exploring the Calcitonin Receptor Relationship With Bone Resorption in Odontogenic Cysts.","authors":"Maria Luiza Diniz de Sousa Lopes, Débora Frota Colares, Tiago João da Silva Filho, Laura Priscila Barboza de Carvalho, Lélia Batista de Souza, Éricka Janine Dantas da Silveira","doi":"10.1097/PAI.0000000000001322","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001322","url":null,"abstract":"<p><p>Understanding the pathogenesis of odontogenic cysts (OCs) may facilitate the development of alternative therapeutic strategies and improve patients' quality of life. Given calcitonin's role in regulating bone metabolism and its clinical applications in gnathic bone-destructive lesions, including OCs, this study assessed potential associations between CTR and the bone resorption markers receptor activator of nuclear factor kappa B ligand (RANKL) and tumor necrosis factor alpha (TNF-α) in OCs. Immunohistochemical analyses were performed on 20 radicular cysts (RCs), 20 radicular residual cysts (RRCs), and 27 dentigerous cysts (DCs). RANKL expression in the epithelial lining was significantly higher in RCs and RRCs compared with DCs ( p =0.039 and p =0.046, respectively). In RCs, significant positive correlations were found between epithelial RANKL and capsular CTR ( p =0.039), epithelial TNF-α and capsular TNF-α ( p =0.037), and epithelial TNF-α and capsular CTR ( p =0.005). In RRCs, epithelial RANKL correlated positively with epithelial TNF-α ( p =0.007) and capsular CTR correlated positively with capsular TNF-α ( p =0.041), whereas epithelial RANKL correlated negatively with capsular TNF-α ( p =0.009). In DCs, significant positive correlations were observed between epithelial and capsular RANKL ( p <0.001) and between epithelial and capsular TNF-α ( p =0.019). These findings suggest that CTR contributes to the pathogenesis of DCs, RCs, and RRCs, and highlight the involvement of RANKL and TNF-α in the biological behavior of these cysts. The interplay among these proteins may promote either osteolytic or osteogenic activity depending on the cystic microenvironment.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679905","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}
Amira Emad Elwy, Ahmed Hamed Shuaib, Sally Salah Abdel-Hakeem, Mohamed Kamal El-Kherbetawy
{"title":"Immunohistochemical Expression of Cyclin D1 in Phyllodes Tumors: Insights Into Tumor Progression and Prognosis.","authors":"Amira Emad Elwy, Ahmed Hamed Shuaib, Sally Salah Abdel-Hakeem, Mohamed Kamal El-Kherbetawy","doi":"10.1097/PAI.0000000000001303","DOIUrl":"10.1097/PAI.0000000000001303","url":null,"abstract":"<p><p>Phyllodes tumors (PTs) are rare fibroepithelial breast tumors, albeit clinically significant. This study was implemented to investigate the immunohistochemical (IHC) expression of cyclin D1 in PT subtypes and in metaplastic spindle cell carcinoma. Fifty-three resected cases of PT subtypes were analyzed. IHC analysis assessed the percentage of positive stromal tumor cells and the intensity of cyclin D1 staining. The score was classified as either negative, low, or high positive. Statistical analysis was implemented to evaluate the outcomes. Significant variations in scores were observed among various subtypes of PT, with cyclin D1 exhibiting positive nuclear expression in the stromal component of borderline and malignant tumors ( P =0.001). Malignant PTs also showed significantly different cyclin D1 expression compared with triple-negative metaplastic spindle cell carcinoma ( P =0.028). Tumor recurrence was significantly associated with high cyclin D1 expression ( P =0.013). Receiver Operating Characteristic (ROC) curve analysis demonstrated moderate discriminatory ability, with an area under the curve (AUC) of 0.701 (95% CI: 0.535-0.856, P =0.023). Univariate analysis confirmed high cyclin D1 expression as a predictor of recurrence ( P =0.035). In conclusion, cyclin D1 overexpression provides insights into tumor progression and prognosis in PTs. Notably, positive cyclin D1 expression in metastatic malignant PT could be a diagnostic challenge, if not carefully considered within clinical context. Furthermore, the significant difference in cyclin D1 expression between malignant PT and triple-negative metaplastic spindle cell carcinoma highlights its potential utility in distinguishing between them.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"69-76"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109524","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}
Glória Maria de França, Cláudia Nunes de Oliveira, Roseana de Almeida Freitas, Pedro Paulo de Andrade Santos, Hébel Cavalcanti Galvão
{"title":"Interrelationship Between SHH and TGF-beta in the Formation of Odontomas.","authors":"Glória Maria de França, Cláudia Nunes de Oliveira, Roseana de Almeida Freitas, Pedro Paulo de Andrade Santos, Hébel Cavalcanti Galvão","doi":"10.1097/PAI.0000000000001300","DOIUrl":"10.1097/PAI.0000000000001300","url":null,"abstract":"<p><p>The SHH signaling regulates cell proliferation in the ectomesenchyme, thus controlling tooth morphogenesis, while TGF-ß and bone morphogenetic proteins (BMPs) have been associated with reactionary and reparative dentinogenesis. The aim of this study was to investigate the role of signaling proteins in odontogenesis and odontoma formation. In this retrospective cross-sectional study, we analyzed the immunohistochemical expression of TGF-ß, BMP4, and SHH pathway proteins in 23 compound odontomas, 21 complex odontomas, and 17 tooth germs. The results demonstrated immunoexpression of BMP4, especially in the ectomesenchyme of complex odontomas (median=33.7; P <0.001). SHH was more immunoexpressed in the epithelium of tooth germs ( P <0.001) and in the ectomesenchyme of complex odontomas ( P =0.029). Similarly, TGF-ß exhibited higher immunoexpression in the epithelium of tooth germs ( P <0.001) and in the ectomesenchyme of complex odontomas ( P =0.002). SHH was more immunoexpressed in the ectomesenchyme of odontomas and in the inner enamel epithelium of tooth germs. Furthermore, SHH and BMP4 were significantly correlated. In developing teeth, the highest concentrations of these proteins were found in the odontogenic epithelium during the bud and cap stages. Differential expression occurred mainly in the ectomesenchyme of tumors, indicating that this component is indeed more proliferative.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"77-85"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954913","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":"A Practical Approach to the Diagnosis of Liver Metastases from Cancer of Unknown Primary: Application of Immunohistochemistry and an Update.","authors":"Ali Koyuncuer, Tolga Canbak, Aylin Acar","doi":"10.1097/PAI.0000000000001295","DOIUrl":"10.1097/PAI.0000000000001295","url":null,"abstract":"<p><p>Cancers of unknown primary (CUP) are tumors whose site of origin remains undetectable despite thorough clinical, radiologic, and histopathologic evaluations. They make up about 2% to 3% of all epithelial tumors and generally have a poor prognosis. Immunohistochemical (IHC) markers complement epidemiological and histomorphologic approaches to determine tumor type, subtype, and primary site, influencing patient prognosis, outcome, and treatment. This retrospective observational study examined patients who underwent liver biopsies for hepatic metastasis between January 2022 and January 2024. Data on age, gender, liver segment localization, tumor number and size, histomorphology, and IHC work-up were analyzed. The average age of metastatic patients was 62±12 years, with 85.5% aged 50 or older. Males slightly outnumbered females (51.1% vs. 49.9%). On average, there were 1.8 metastatic foci per case. The most common metastasizing tumors included colorectal (30.5%), pancreaticobiliary (29%), breast (8.4%), lung (6.9%), and lymphomas (4.6%). Histomorphologically, 66.4% were adenocarcinomas, followed by poorly differentiated tumors (9.2%) and neuroendocrine neoplasms (8.4%). At the time of biopsy, 33.6% had initial CUP (i-CUP), 22.9% had their primary site detected by IHC, and 10.7% had true CUP (t-CUP). On average, 9.4 IHC markers were used per case, rising to 13.8 in t-CUP cases. Significant correlations were found between histomorphologic patterns, primary site detection, and IHC marker usage ( P =0.01 and 0.02). IHC continues to enhance the diagnosis and treatment of metastatic liver tumors with its use of tumor-specific or organ-specific antibodies, including newly developed transcription factors, aiding pathologists in personalized medicine.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"49-68"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592743","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}
Shivangni Rajoria, Priya Kumar, Anshuman Kumar, Hema M Aiyer, Garima Rawat, Aadithya B Urs
{"title":"Immunohistochemical Analysis of STAT3 and ITGB6 in Oral Squamous Cell Carcinoma: Prognostic Relevance for Lymph Node Metastasis and Overall Survival.","authors":"Shivangni Rajoria, Priya Kumar, Anshuman Kumar, Hema M Aiyer, Garima Rawat, Aadithya B Urs","doi":"10.1097/PAI.0000000000001309","DOIUrl":"10.1097/PAI.0000000000001309","url":null,"abstract":"<p><strong>Background: </strong>Signal transducer and activator of transcription 3 (STAT3), a transcription factor and Integrin αvβ6 (ITGB6), a transmembrane protein are upregulated in a wide array of cancers. Oral squamous cell carcinoma (OSCC) has an invasive potential and a tendency to metastasize chiefly to cervical lymph nodes ultimately affecting the survival rate. This study endeavours to determine the role and correlation of STAT3 and ITGB6 in OSCC with and without lymph node metastasis and their association with overall survival.</p><p><strong>Material and methods: </strong>A total of 100 cases of OSCC were included, comprising 50 cases with lymph node metastasis (nodal group) and 50 without nodal metastasis (non-nodal group). All cases were assessed histologically for prognostic scoring and were immunohistochemically stained using STAT3 and ITGB6 markers. Clinicopathological parameters with STAT3 and ITGB6 immunoexpressions along with overall survival with a mean follow-up period of 48 months were assessed as Immunoreactive score (IRS).</p><p><strong>Results: </strong>Significantly stronger expression (IRS 2) of STAT3 and ITGB6 was observed in OSCC cases with lymph node metastasis. The nodal group with stronger STAT3 and ITGB6 expressions showed lower survival although no statistically significant differences were found. These markers showed prognostic significance independently, but no significant correlation was observed between the 2.</p><p><strong>Conclusion: </strong>On the basis of our findings, STAT3 and ITGB6 were statistically associated with lymph node metastasis. Thus, we hypothesised that their increased expression can lead to the migration of cancer cells, resulting in lymph node metastasis and affecting overall survival. Further understanding of the signalling pathways mediating STAT3 and ITGB6 may help identify valid therapeutic targets for OSCC patients.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"86-94"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088689","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}
Azfar Neyaz, Nuha Shaker, M-Nasan Abdul Baki, Hamdi Surakji, Rayan Rammal, Mariel Bedell, Ihsan Baroudi, Akila Mansour, Andrew M Bellizzi, Ibrahim Abukhiran
{"title":"Prognostic Significance of Abnormal MTAP and p16 Expression in Gastrointestinal Stromal Tumors (GISTs).","authors":"Azfar Neyaz, Nuha Shaker, M-Nasan Abdul Baki, Hamdi Surakji, Rayan Rammal, Mariel Bedell, Ihsan Baroudi, Akila Mansour, Andrew M Bellizzi, Ibrahim Abukhiran","doi":"10.1097/PAI.0000000000001299","DOIUrl":"10.1097/PAI.0000000000001299","url":null,"abstract":"<p><p>Molecular alterations in the CDKN2A gene have been identified as a poor prognostic marker in a small subset of gastrointestinal stromal tumors (GISTs). Investigations into the potential utility of p16 protein loss by immunohistochemistry (IHC) as a surrogate marker of CDKN2A deletion have revealed contradictory findings in various cancers. Recently, high concordance of MTAP and CDKN2A codeletion has been identified, suggesting the potential use of MTAP as a surrogate marker for CDKN2A deletion in various other tumor types. Our objective was to investigate the prognostic significance of MTAP and p16 expression in GISTs, with the aim of shedding light on its potential in refining risk stratification and optimizing patient management. We assembled our institutional cohort of 225 surgically resected GISTs. MTAP and p16 immunohistochemical stains were performed on the tissue microarrays, and we recorded the cytoplasmic expression (for MTAP) or cytoplasmic/nuclear (for p16) as negative (loss), weak to moderate/heterogenous (wild type), or strong diffuse (overexpression). We found MTAP loss in 11 (5%) cases and overexpression in 40 (18%), while p16 overexpression was found in 5 (2%) cases and loss in 45 (21%). Overexpression as well as loss of MTAP and p16 expression correlated with the presence of epithelioid histology (either pure or mixed with a spindle cell component), higher grade and pT-stage, necrosis, higher NCCN risk groups, and widespread disease at presentation. Overexpression as well as loss of MTAP and p16 expression predicts shortened progression-free survival and is associated with various known poor prognostic clinicopathologic parameters.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"119-128"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115342","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}
Sebastian Fernandez-Pol, Kelly Young, Ivy Mangonon, Ellen Gomulia, Yasodha Natkunam, Megan L Troxell
{"title":"Immunohistochemistry New Instrument Validations: Why Your Validation Plan Matters.","authors":"Sebastian Fernandez-Pol, Kelly Young, Ivy Mangonon, Ellen Gomulia, Yasodha Natkunam, Megan L Troxell","doi":"10.1097/PAI.0000000000001306","DOIUrl":"10.1097/PAI.0000000000001306","url":null,"abstract":"<p><p>Validation in immunohistochemistry is a well-established and regulated process when it pertains to assays. However, little guidance currently exists on how to best validate automated instrumentation, including validation of a completely new platform or validation of a new instrument of the same make and model. Here, we share insights gained from our laboratory's recent instrument validations, identifying key challenges such as variability in stain intensity related to tissue location on slides and the prevalence of \"cold zones\" affecting stain interpretation. Through these scenarios, we emphasize the importance of a robust validation plan that incorporates diverse assay-tissue combinations, strategic tissue placement, and the evaluation of larger tissue sections. In addition, we advocate for vendors to enhance their instrument testing protocols to proactively identify subtle performance issues. We propose a framework for more effective validation strategies, including emerging quantitative technologies in this field.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"129-132"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168771","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}
Dennis P O'Malley, Skyler Stephan, Andrew M Bellizzi
{"title":"CD71 Expression in Hodgkin Cells.","authors":"Dennis P O'Malley, Skyler Stephan, Andrew M Bellizzi","doi":"10.1097/PAI.0000000000001294","DOIUrl":"10.1097/PAI.0000000000001294","url":null,"abstract":"","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"133"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598477","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}
Sanjana S James, Hari S Malla, Vishnupriya Gopalakrishnan, Mukund N Sable, Arunkumar Sekar, Sumit Bansal, Saroj K Das Majumder, Suvendu Purkait
{"title":"Peroxisome Proliferator-Activated Receptor (PPAR) Expression Correlates With Tumor Grade and Prognostic Outcome in Meningiomas.","authors":"Sanjana S James, Hari S Malla, Vishnupriya Gopalakrishnan, Mukund N Sable, Arunkumar Sekar, Sumit Bansal, Saroj K Das Majumder, Suvendu Purkait","doi":"10.1097/PAI.0000000000001301","DOIUrl":"10.1097/PAI.0000000000001301","url":null,"abstract":"<p><p>The present study assessed the expression of different isoforms of PPAR, an important regulator of cell metabolism and proliferation, in meningiomas and correlated it with different clinicopathological variables and clinical outcomes. A total of 238 meningiomas were studied, including grade 1 (n=133), grade 2 (n=66), grade 3 (n=2), and brain-invasive otherwise benign meningiomas (BIOB) (n=37). The expression of PPAR-γ, phosphorylated PPAR-γ, and PPAR-β was assessed by immunohistochemistry. A semiquantitative grading was used to classify the cases into high and low expression. High nuclear and cytoplasmic immunoreactivity of PPAR-γ was significantly more frequent in grade 2 meningiomas than in grade 1 or BIOB ( P =0.023, 0.006 for nuclear expression, and 0.001, 0.004 for cytoplasmic expression, respectively). It was also associated with higher proliferative activity and p53 positivity ( P =0.002 and 0.001, respectively). Phosphorylated PPAR-γ and PPAR-β expression did not show any association with grade. PPAR-γ immunoreactivity, extent of resection, and histologic grade were associated with overall survival (OS) [ P =0.031 (nuclear)/0.005 (cytoplasmic), 0.002, and <0.001, respectively]. Interestingly, BIOB cases had OS similar to grade 2 tumors, significantly shorter than that of their grade 1 counterparts. Further, high PPAR-γ expression was associated with better outcomes with no death in patients who received adjuvant radiotherapy. The present study, for the first time, highlights that PPAR expression is implicated in the pathobiology of meningiomas and has prognostic implications, especially in cases receiving radiotherapy. Considering the availability of PPAR modulatory drugs, it may be an important therapeutic target. In addition, the meticulous examination of the brain invasion still holds significant promise for prognostication.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":"34 2","pages":"108-118"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358328","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}