Human pathology最新文献

{"title":"TSC gene-associated lesions of the lung.","authors":"Fatime Szalai, Ildiko Krencz, Charles D Burger, Anna Kornafeld, Andras Khoor","doi":"10.1016/j.humpath.2026.106173","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106173","url":null,"abstract":"<p><p>Pathogenetic alterations of tumor suppressor genes TSC1 and TSC2 are responsible for the development of tuberous sclerosis complex (TSC) and various sporadic diseases, including sporadic lymphangioleiomyomatosis (LAM). TSC can be inherited and non-inherited and is characterized by indolent tumor formation in multiple organs. The most important pulmonary manifestation of TSC is LAM. It affects the majority of female and a small subset of male patients, heavily impacting their quality of life and survival. It is a cystic lung disease, which is now considered a PEComa-type neoplasm. In addition to the TSC-associated form (TSC-LAM), LAM can also occur sporadically (S-LAM), almost exclusively in women. Both forms present with proliferation of immature smooth muscle cells, resulting in cystic destruction of the pulmonary parenchyma and emergence of respiratory symptoms, including dyspnea and pneumothorax. Currently, sirolimus is the only FDA-approved treatment option for LAM patients; however, a subgroup of patients either do not respond or tolerate therapy. Recently published data has shed light on the heterogeneity of LAM and the importance of the tumor microenvironment, which may serve as new aspects for future research. Other TSC gene-associated lesions of the lung include multifocal micronodular pneumocyte hyperplasia (MMPH) and non-LAM PEComa (clear cell sugar tumor). While MMPH may not be progressive or require clinical treatment, it might require differentiation from atypical adenomatous hyperplasia or lepidic adenocarcinoma of the lung.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106173"},"PeriodicalIF":2.6,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of NPM1 immunohistochemistry with mutation subtypes, clinicopathologic variables and molecular testing in AML with NPM1 mutation","authors":"Sharon Koorse Germans ,&nbsp;Olga K. Weinberg ,&nbsp;Weina Chen ,&nbsp;Miguel Cantu ,&nbsp;Mingyi Chen ,&nbsp;Dwight Oliver ,&nbsp;Prasad Koduru ,&nbsp;Lindsay Bigham","doi":"10.1016/j.humpath.2026.106073","DOIUrl":"10.1016/j.humpath.2026.106073","url":null,"abstract":"<div><h3>Background</h3><div>Nucleophosmin 1 <em>(NPM1</em>) mutations define a major molecular subtype of acute myeloid leukemia (AML). Although RT-PCR and next-generation sequencing (NGS) remain the gold standard for diagnosis and minimal/measurable residual disease (MRD) assessment, NPM1 mutant-specific immunohistochemistry (NPM1m IHC) using monoclonal antibodies presents a rapid and cost-effective alternative. Correlation between NPM1m IHC patterns and specific NPM1 mutation subtypes remain underexplored.</div></div><div><h3>Objectives</h3><div>Evaluate the diagnostic utility of NPM1m IHC in AML with <em>NPM1</em> mutation and to assess its correlation with mutation subtypes, morphologic features, cytogenetic profiles, co-mutations, and clinical outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort of 36 AML cases with confirmed <em>NPM1</em> mutations (2018-2024) were analyzed for clinicopathologic variables, cytogenetics, PCR/NGS data, and NPM1m IHC results with subgroup analysis between Type A (n = 28) and non-Type A (n = 8) mutations.</div></div><div><h3>Results</h3><div>NPM1m IHC positivity was observed in all insertional <em>NPM1</em> mutation subtypes with two distinct staining patterns: homogeneous and two-toned, with two-toned pattern more frequent in Type A mutations. Non-Type A mutations were more often associated with complex karyotypes and showed a trend toward less frequent <em>FLT3</em> co-mutations. Monocytic differentiation and cup-like nuclear morphology were assessed in both subgroups. No significant difference in survival or remission rates was observed between groups, although Type A mutations exhibited higher rates of dysplasia (p = 0.03).</div></div><div><h3>Conclusion</h3><div>NPM1m IHC is a sensitive and timely surrogate marker for insertional <em>NPM1</em> mutations, correlating well with molecular results and useful in both immediate diagnosis and MRD evaluation. This study reveals subtype-specific morphologic and cytogenetic associations and highlights the need for further investigation into non-insertional <em>NPM1</em> mutations and their detection challenges.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106073"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostatic adenocarcinoma identified on transurethral resection of bladder tumor: A clinicopathologic series of a diagnostically relevant potential pitfall","authors":"Douglas Jian-Xian Wu,&nbsp;Richard Pacheco,&nbsp;Emily Chan,&nbsp;Alarice Cheng-Yi Lowe,&nbsp;Ankur R. Sangoi","doi":"10.1016/j.humpath.2026.106059","DOIUrl":"10.1016/j.humpath.2026.106059","url":null,"abstract":"<div><div>Over the past 2 decades, we have increasingly encountered prostatic adenocarcinoma (PCA) presenting as urinary bladder tumors in routine practice as well as among consultation/medicolegal cases. Given the ramifications of a potential misdiagnosis of PCA as urothelial carcinoma (UC), herein we explore clinicopathologic features among a large cohort of PCA identified on transurethral bladder tumor resection (TURBT). A retrospective re-review identified 54 TURBTs containing PCA from a single tertiary care academic hospital (2003–2025). Of the 27 patients with prior PCA history, urologists were concerned for PCA in 86 %, but history/suspicion was only conveyed in 32 % of accompanying specimen requisition sheets. For patients without PCA history, urologists were occasionally (29 %) suspicious for PCA, mentioning this possibility on requisition sheets in all (100 %) of cases. Most tumors were from the bladder neck or base (72 %). Pseudopapillary/papillary-like growth pattern was often seen (46 %). The predominant architecture was solid or nested/corded (70 %) followed by glandular (26 %) and acinar (4 %). Nuclei in most cases were uniform/round (89 %) with prominent nucleoli predominant in most cases (56 %) while the cytoplasm was more often “pale/bubbly” (72 %) versus “dense/glassy” (28 %). Pseudopapillary/papillary-like growth compounded with solid to nested architecture within PCA can mimic UC on TURBT specimens, although nuclear features/prominent nucleoli can be a helpful clue. While clinical/cystoscopic findings (e.g. tumor site) may suggest PCA on TURBT, this information does not always accompany the specimen, requiring confirmatory chart review for putative cases as well as judicious use of immunohistochemistry.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106059"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and clinical significance of 1p36 chromosomal aberrations in differentiating hepatocellular carcinoma from other hepatobiliary cancers","authors":"Wantakan Ngamsangiam ,&nbsp;Sutheemon Techa-ay ,&nbsp;Prakasit Sa-ngiamwibool ,&nbsp;Sasithorn Watcharadetwittaya ,&nbsp;Raksawan Deenonpoe ,&nbsp;Anchalee Techasen ,&nbsp;Adjima Luechine ,&nbsp;Watcharin Loilome ,&nbsp;Malinee Thanee","doi":"10.1016/j.humpath.2026.106053","DOIUrl":"10.1016/j.humpath.2026.106053","url":null,"abstract":"<div><div>Differentiating among hepato-pancreato-biliary (HPB) cancers like cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), pancreatic cancer (PC), and gallbladder cancer (GBC) can be challenging. To address this, our study used fluorescence in situ hybridization (FISH) to identify 1p36 chromosomal abnormality patterns in 100 HPB cancer patients. We found consistent 1p36 loss in CCA, IPNB, GBC, and PC, while HCC uniquely exhibited normal, loss, and gain patterns. Notably, this 1p36 gain showed a sensitivity was 45.71 % and specificity was 100 % for differentiating HCC from CCA and other HPB cancers, while 1p36 loss proved highly sensitive (100 %) and specific (85.71 %) for distinguishing CCA from HCC, though its ability to differentiate CCA from others was limited. Beyond diagnosis, a high burden of 1p36 loss was a significant prognostic factor for shorter overall survival in CCA (p = 0.024) and in the combined CCA/IPNB cohort (p = 0.015). More importantly, 1p36 loss also significantly correlated with tumor differentiation in CCA (p &lt; 0.05). These results suggest that assessment of 1p36 status by FISH may serve as a complementary molecular approach to conventional histopathology and immunohistochemistry, providing additional differential diagnostic HCC from CCA and other diagnostically challenging HPB cancers and serve as promising prognostic biomarkers for CCA and IPNB.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106053"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100 expression and SDHB status define distinct biological subsets of bladder paraganglioma","authors":"Huili Li ,&nbsp;Andres Matoso","doi":"10.1016/j.humpath.2026.106072","DOIUrl":"10.1016/j.humpath.2026.106072","url":null,"abstract":"<div><div>Bladder paraganglioma is an exceptionally rare neuroendocrine tumor with important diagnostic and prognostic implications. We retrospectively analyzed 110 bladder paragangliomas diagnosed between 2000 and 2025 to better characterize clinicopathologic features, immunophenotypic patterns, and clinical outcomes, with particular emphasis on S100, SOX10, and SDHB immunohistochemistry. The cohort showed a slight female predominance (F:M = 1.34) and a mean age at diagnosis of 62.7 years. Most tumors involved the muscularis propria, supporting a bladder wall origin. Among cases with available S100 staining, nearly half (48.5%) demonstrated diffuse, strong S100 expression in both chromaffin and sustentacular cells, an unusual pattern that frequently caused diagnostic confusion and was the reason for consultation. In contrast, SOX10 expression remained restricted to sustentacular cells in all tested tumors, underscoring its reliability as a Schwannian marker. Loss of SDHB expression was identified in 14.5% of tumors and was significantly associated with younger age, male sex, absence of diffuse S100 expression, and metastatic disease. All S100-positive tumors retained SDHB expression. Among patients with available follow-up, 20% developed metastatic disease, with a 5-year metastatic rate of 38.5%; most metastatic tumors showed SDHB loss and were S100-negative. No paraganglioma-related deaths were documented. These findings demonstrate that diffuse S100 positivity in bladder paraganglioma is relatively common and represents a significant diagnostic pitfall. Importantly, S100-positive tumors appear to be associated with intact SDHB expression and a potentially less aggressive phenotype, whereas SDHB loss identifies a higher-risk subset with increased metastatic potential.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106072"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicular lymphoma with signet ring cell morphology: Clinicopathologic analysis of 31 cases","authors":"Xenia Parisi ,&nbsp;L. Jeffrey Medeiros","doi":"10.1016/j.humpath.2026.106071","DOIUrl":"10.1016/j.humpath.2026.106071","url":null,"abstract":"<div><div>We report 31 cases of follicular lymphoma (FL) with signet ring (SR) cells, representing &lt;0.05% of FLs diagnosed at our institution. The cohort includes 16 women and 15 men with a median age of 65 years (range, 26–87). All patients presented with lymphadenopathy. Twenty-three (74%) patients had advanced stage disease and 8 (26%) had localized (stage I or II) disease. Twenty-one (68%) patients underwent excisional biopsy, 8 core needle biopsy and 2 fine needle aspiration. All 29 neoplasms with biopsy specimens had a follicular pattern, at least in part, but 9 had diffuse areas. These neoplasms were grade 1-2 in 19 cases and grade 3A in 10 cases. In addition, 1 patient had FL grade 1-2 in the nasopharynx and FL grade 3A FL in a regional lymph node and 1 patient had FL grade 3A (25% of the specimen) associated with diffuse large B-cell lymphoma. We semi-quantified the percentage of SR cells as follows: 5-10% in 3 cases, 11-25% in 8, 26-50% in 9, 51-75% in 10 and &gt; 75% in 1 neoplasm. Immunophenotypic analysis using immunohistochemistry was performed in all cases and flow cytometry immunophenotypic analysis was performed in 24 cases. All neoplasms were positive for pan-B-cell markers and lacked T-cell antigens. CD10 was positive in 28 of 30 (93%) cases, and BCL2 and BCL6 were positive in all 20 and 18 cases assessed, respectively. <em>IGH::BCL2</em> was detected in all 10 cases tested by fluorescence in situ hybridization. Targeted next-generation sequencing analysis performed successfully on 4 cases identified recurrent mutations in genes often involved in FL, such as <em>KMT2D</em> and <em>TNFRSF14.</em> In conclusion, in this retrospective study we provide the largest case series of FL-SR. We show that SR cells can be numerous in FL, but otherwise these cases resemble classic FL. We also provide results of next generation sequencing data on 4 cases which heretofore has not been reported.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106071"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute leukemia with BCL11B rearrangements: Genetic landscape, BCL11B expression, and therapeutic response","authors":"Guilin Tang ,&nbsp;Sa A. Wang ,&nbsp;Wei Ying Jen ,&nbsp;L. Jeffrey Medeiros ,&nbsp;Wei Wang ,&nbsp;Hong Fang ,&nbsp;Shimin Hu ,&nbsp;Nitin Jain ,&nbsp;Elias Joseph Jabbour ,&nbsp;Ying S. Zou ,&nbsp;Jie Xu","doi":"10.1016/j.humpath.2026.106057","DOIUrl":"10.1016/j.humpath.2026.106057","url":null,"abstract":"<div><div>Rearrangements involving <em>BCL11B</em> have emerged as important structural variants in acute leukemias with T lineage differentiation, yet their prevalence and biological significance remain incompletely defined. Using optical genome mapping (OGM), we identified <em>BCL11B</em> rearrangements in 25 of 2325 hematologic malignancies, restricted to T-lymphoblastic leukemia particularly early T precursor (ETP) subtype, mixed phenotype acute leukemia T/myeloid, and rare acute myeloid leukemia. Breakpoints at 14q32.2 were highly variable and largely cryptic by karyotyping. Twelve putative partner genes were detected, including four previously reported (<em>TLX3, ARID1B, CDK6, and CCDC26</em>) and 8 novel partners (<em>FOXF1, TLX1, NUP98, LMO2, GAPDHP71, GRM4, TNFAIP3</em>, and <em>TRRAP)</em>. Evaluation of BCL11B expression showed that rearrangements involving partners currently considered “<em>BCL11B</em>-activated”, such as <em>ARID1B</em>, <em>CCDC26</em>, and <em>CDK6</em>, did not uniformly associate with <em>BCL11B</em> overexpression. Conversely, cases with <em>TLX3::BCL11B</em>, previously thought to upregulate <em>TLX3</em>, demonstrated strong <em>BCL11B</em> expression (3 of 4 cases). Clinically, newly diagnosed patients, most treated with venetoclax based regimens, achieved high remission rates. Our data delineate the structural diversity of <em>BCL11B</em> rearrangements identified by OGM and show that <em>BCL11B</em> activation cannot be reliably inferred from partner gene identity alone. BCL11B immunohistochemistry as a practical surrogate for assessing <em>BCL11B</em> activation is recommended in routine practice.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106057"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epstein-Barr virus associated gastric carcinoma: A clinicopathologic study with recognition of a distinctive reticular histologic pattern","authors":"Julia Gallardo,&nbsp;Emrah Gumusgoz ,&nbsp;James M. Mitchell,&nbsp;Suntrea Hammer,&nbsp;Zhikai Chi,&nbsp;Purva Gopal,&nbsp;Dipti M. Karamchandani","doi":"10.1016/j.humpath.2026.106054","DOIUrl":"10.1016/j.humpath.2026.106054","url":null,"abstract":"<div><div>Existing data characterize “classic\" Epstein-Barr virus (EBV) positive gastric carcinoma (GC) histologically as GC with lymphoid stroma (or lymphoepithelioma-like or medullary) exhibiting sheets or syncytia of malignant cells with prominent intratumoral lymphocytes. This diagnosis has clinical implications, given the associated frequent programmed death-ligand 1 gene amplification, and clear benefit from immunotherapy. However, there appears to be a paucity of published data regarding characteristic histologic features of EBV-GC. We evaluated 19 EBV-GC specimens (11 biopsies; 8 resections) retrieved from 13 patients and found that a unique reticular pattern was identified in 17 of 19 (89 %) specimens, either as an exclusive pattern in 26 %, or as a mixed pattern in 63 % specimens. Most patients were male (85 %), with an average age of 61.5 years, mostly of Hispanic or Black (77 %) ethnicity, and showed a predilection for proximal stomach (69 %). Associated prominent intratumoral inflammation was seen in cases retrieved from all patients (lymphocytic: 7, mixed: 6). Although a similar lace-like pattern has been implicitly cited in association with early stage EBV-GC, we report a unique reticular pattern with intratumoral inflammation that was seen more commonly than widely known “classic” histology and was even seen in association with advanced pathologic stage. We propose that ancillary EBV testing be performed on all gastric tumors with this distinctive pattern, and with other patterns with prominent (including mixed) intratumoral inflammation, to screen for EBV-GC cases, thus detecting patients who may be eligible for immunotherapy with important therapeutic implications.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106054"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal active colitis: Diagnostic relevance and long-term clinical outcomes","authors":"Aya B. Soubra,&nbsp;Selim M. Nasser","doi":"10.1016/j.humpath.2026.106070","DOIUrl":"10.1016/j.humpath.2026.106070","url":null,"abstract":"<div><h3>Background</h3><div>Focal active colitis (FAC) is a histopathologic finding characterized by focal neutrophilic crypt injury without chronic architectural changes. Its clinical implications, particularly its association with inflammatory bowel disease (IBD), remain debated.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed colorectal biopsies diagnosed as FAC (2005–2024) at a tertiary center in Lebanon. Adult patients (&gt;18 years) with isolated FAC and available clinical follow-up were included. Clinical outcomes, endoscopy, and subsequent diagnoses were analyzed.</div></div><div><h3>Results</h3><div>419 patients had complete follow-up data. Mean age was 52.5 years; 51.5% were female. Abdominal pain was the most common presentation (57.5%). Colonoscopy was normal in 73%. During a mean 26-month follow-up, 9 patients (2.15%) developed IBD (4 Crohn's disease, 3 ulcerative colitis, 2 unclassified). IBS was diagnosed in 33.2%, infectious colitis in 11.2%, drug-induced colitis in 8.6%, diverticular disease in 4.5%, and ischemic colitis in 0.7%. 25.3% had no identifiable etiology with negative follow-up. FAC was incidental in 10.5% and persistent in 3.8%. No histologic features predicted progression to IBD.</div></div><div><h3>Conclusion</h3><div>In this 19-year, 419-patient study, FAC was most often linked to IBS, infection, or drug-induced injury, with only 2.15% progressing to IBD. No predictive histologic features were identified. FAC remains a nonspecific finding; careful follow-up is warranted in symptomatic patients, while incidental cases are usually clinically insignificant.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106070"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation analysis of TP53 missense mutations and p53 protein expression patterns in endometrial carcinoma","authors":"Ying Yang ,&nbsp;Shu Sun ,&nbsp;Yun Xi ,&nbsp;Chenyang Xu ,&nbsp;Rui Zhu ,&nbsp;Wenjuan Yin ,&nbsp;Yanyan Zhan ,&nbsp;Dan Su","doi":"10.1016/j.humpath.2026.106056","DOIUrl":"10.1016/j.humpath.2026.106056","url":null,"abstract":"<div><div>p53 abnormality (p53 abn) subtype is a critical category in endometrial carcinoma (EC) molecular classification, yet clinical diagnosis often relies solely on p53 immunohistochemistry (IHC) staining or <em>TP53</em> gene sequencing. This study aimed to explore the correlation between <em>TP53</em> genotype and p53 protein expression in EC with <em>TP53</em> missense mutations, as well as the clinical and prognostic significance of their discordance. A total of 253 EC specimens from Zhejiang Cancer Hospital (January 2021–November 2023) were retrospectively collected; 103 cases with isolated <em>TP53</em> missense mutations were screened via next-generation sequencing (NGS) and subjected to p53 IHC. Variant interpretation revealed that six mutations in six patients were of uncertain significance. Among the remaining patients, 54 (involving 36 variants) showed concordance between IHC phenotype and genotype: high frequency mutations such as R273H, Y220C, M237I, and V272L all exhibited mutant p53 expression, whereas V31I showed wild-type expression. Another 43 patients (involving 13 variants) displayed discordance between genotype and IHC phenotype. Clinicopathological comparison revealed that the discordant group was younger (&lt;60 years) and dominated by non-aggressive histology (all <em>P</em> &lt; 0.05). The discordant group showed better survival trends than the concordant group, with no statistically significant difference in disease-free survival (DFS) (<em>P</em> = 0.057). In conclusion, p53 expression is heterogeneous in EC with <em>TP53</em> missense mutations; gene-protein discordance correlates with distinct clinicopathological features. Integrating genetic and protein detection results is recommended for risk stratification and individualized treatment.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106056"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}