Applied immunohistochemistry & molecular morphology : AIMM最新文献

{"title":"Integrating Clinical and Molecular Insights: CTPS1 as a Key Biomarker of Tumor Progression and Prognosis in Colorectal Adenocarcinoma.","authors":"Dina Moustafa Thabit, Rofida Khalifa, Dalia M Thabet","doi":"10.1097/PAI.0000000000001315","DOIUrl":"10.1097/PAI.0000000000001315","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of global cancer-related mortality. Cytidine triphosphate synthase 1 (CTPS1) is an essential enzyme for DNA synthesis and cell cycle progression. While CTPS1 has been implicated in the pathogenesis of various malignancies, its clinical significance in colorectal adenocarcinoma remains poorly defined. This study aimed to investigate the immunohistochemical (IHC) expression of CTPS1 in colorectal adenocarcinoma and evaluate its association with clinicopathological features and survival outcomes. CTPS1 expression was assessed via IHC in 168 colorectal adenocarcinoma specimens and 142 matched adjacent non-neoplastic tissues. Statistical associations with clinicopathological parameters were analyzed using χ2 or Fisher exact tests. Progression-free survival (PFS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and compared via the log-rank test. Multivariate Cox proportional hazards regression was employed to identify independent prognostic factors. CTPS1 expression was significantly upregulated in tumour tissues compared with adjacent normal mucosa (P<0.001). High CTPS1 expression was observed in 55.4% of tumor samples and significantly correlated with advanced T stage, TNM stage, and modified Dukes staging, as well as nodal involvement, distant metastasis, tumor recurrence, and elevated serum CEA levels. Furthermore, elevated CTPS1 was associated with aggressive histologic features, including higher grade, tumor budding, poorly differentiated clusters (PDCs), and tumor deposits. Both PFS and DFS were significantly shorter in patients with high CTPS1 expression (P<0.001). Multivariate analysis confirmed that high CTPS1 expression, along with nodal status and tumor recurrence, was an independent prognostic factor for both PFS and DFS. Therefore, CTPS1 is a robust independent prognostic indicator and a marker of aggressive progression in colorectal adenocarcinoma. These findings suggest that CTPS1 is a promising biomarker for risk stratification and may guide clinical decision-making in the management of CRC.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":"34 3","pages":"195-208"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849075","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":"A Tissue Processing Technique for Improving Slide Preparation Quality of ESD Specimens.","authors":"Shanshan Huang, Xiaodan Fu, Yu Zhang, Ping Wu, Yupeng Chen, Mi Wang, Huinan Lu, Sheng Zhang, Guoping Li","doi":"10.1097/PAI.0000000000001323","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001323","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of endoscopic submucosal dissection (ESD) procedures and subsequent treatment is predominantly reliant on precise pathologic evaluation, intricately linked to specimen sampling and paraffin sectioning. Despite established guidelines in China for ESD specimen processing, the postsampling process remains intricate and error-prone. This study investigates the impact of various placement and labeling methods following ESD sampling on the quality of paraffin slides and the precision of pathologic diagnoses, with the ultimate goal of identifying the most effective approach.</p><p><strong>Methods: </strong>We selected 45 ESD specimens and used 3 distinct postsampling placement and labeling methods: the conventional method, the sponge sandwich placement method, and the sponge interstitial vertical embedding method. Routine HE, IHC, and specific staining were performed to evaluate the effect.</p><p><strong>Results: </strong>Our findings demonstrated that both the sponge sandwich placement and sponge interstitial vertical embedding methods resulted in superior HE preparation quality compared with the conventional method, with no discernible difference in HE preparation quality between the sponge sandwich and sponge interstitial vertical embedding methods. It was also verified by IHC and special staining. Nevertheless, the sponge sandwich placement method resulted in irregular marking of the dehydration box, making it challenging for technicians to determine the embedding direction of the specimens without a bulge or without remembering the embedding phenomenon. In contrast, the sponge interstitial vertical placement and labeling embedding method obviates the need to recognize the embedding direction of the specimen and tissues to be embedded; embedding is guided solely by the morphology and direction of the doctor-placed sponge.</p><p><strong>Conclusions: </strong>Based on our laboratory experience, we advocate for the sponge interstitial vertical embedding method.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795035","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":"Solving the Puzzle of Hans' Algorithm (HA) Methodological Shortcomings: Canadian Harmonization of Hans' Algorithm for Diffuse Large B-Cell Lymphoma (DLBCL) and Development of Fit-for-Purpose Modified Hans' Algorithm (mHA).","authors":"Emina Torlakovic, Ariz Akhter, Allam Shawwa, Antonio Maietta, Brian Olsen, Catherine A Ross, Carol Cheung, H Rommel R Seno, Jean Deschênes, Pedro Farinha, Philip Berardi, Monalisa Sur, Muhamad Sadek Almiski, Rasha A ElGamal, Adnan Mansoor","doi":"10.1097/PAI.0000000000001324","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001324","url":null,"abstract":"<p><p>Hans' algorithm (HA) is the most frequently used surrogate biomarker scheme for subtyping Diffuse large B-cell lymphoma (DLBCL) by the cell-of-origin (COO) into GCB and non-GCB subtypes. The originally published positive and negative predictive value (PPV and NPV) against gene expression profiling (GEP) subtypes were less than perfect and were not fully reproducible in published literature. Furthermore, little is known about how the HA performs in clinical practice. The Canadian Association of Pathologists National Standard Committee for High Complexity Testing (CAP-ACP NSCHCT) initiated a Canada-wide project to assess the current diagnostic accuracy of the HA in clinical practice, harmonize the analytical phase of the IHC assays used for HA, and to optimize its overall diagnostic sensitivity and specificity against GEP subtypes. We divided a DLBCL cohort (n=96), where COO was defined by GEP (Lymph2CX, NanoString technologies) into training (TC, N=45) and validation cohort (VC, N=51) and tissue microarray (TMA)-TC and TMA-VC were constructed. Selected major Canadian laboratories applied their routine CD10, Bcl-6, and MUM1 IHC protocols and sent stained slides to the reference laboratory for review. The IHC protocols from laboratories were designated as \"weak\" (1/10), \"moderate\" (4/10), and \"strong\" (5/10) based on their overall analytical sensitivity. The results of the central review HA readouts were compared with GEP results. Furthermore, in TC, the original HA readout was modified to adjust the cutoff to overall IHC protocol sensitivity. The new readout criteria were also assessed in the VC set. The original HA readout showed good results against GEP for low sensitivity protocol only. For all other laboratories that had IHC protocols with moderate and high analytical sensitivity, a readout was adjusted to higher IHC protocol analytical sensitivity using a cutoff of >30% of >2+ staining intensity. This modification yielded significantly improved diagnostic accuracy against GEP even without any changes to the IHC protocols and was widely applicable to the range of analytical sensitivities of IHC protocols, which are currently in use. IHC biomarkers for HA can be highly accurate and harmonized across different laboratories for clinical application if the following criteria are met: (i) testing laboratories use standardized reference materials to set up and monitor analytical sensitivity, and (ii) the pathologist's readout and cutoff are adjusted to the overall IHC protocol analytical sensitivity.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731209","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":"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}

{"title":"ISIMM Page.","authors":"","doi":"10.1097/PAI.0000000000001320","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001320","url":null,"abstract":"","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":"34 2","pages":"1"},"PeriodicalIF":1.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358372","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":"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}

{"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}

{"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}

{"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}