Modern Pathology最新文献

{"title":"Early Genetic Divergence of High-Grade Carcinomas Originating from Low-Grade Serous Ovarian Neoplasms","authors":"M. Herman Chui ,&nbsp;Qianqian Song ,&nbsp;Jiarun Zhu ,&nbsp;Yuchen Jiao ,&nbsp;Brant Wang ,&nbsp;Yeh Wang ,&nbsp;Tian-Li Wang ,&nbsp;Russell Vang ,&nbsp;Ie-Ming Shih","doi":"10.1016/j.modpat.2024.100629","DOIUrl":"10.1016/j.modpat.2024.100629","url":null,"abstract":"<div><div>The current paradigm implicates a fallopian tube precursor as the origin of most ovarian high-grade serous carcinomas (HGSCs). However, a rare subset of HGSCs develop via a distinct pathway from low-grade serous ovarian neoplasms (namely, serous borderline tumors and low-grade serous carcinoma). This alternate pathway for the development of HGSC and other poorly differentiated carcinomas of the ovary is not well understood. To elucidate the molecular pathogenesis and evolutionary trajectory of histologic transformation of low-grade serous neoplasms, we performed whole exome sequencing on microdissected low-grade and higher-grade components from 7 cases of serous borderline tumor or low-grade serous carcinoma associated with a synchronous or metachronous indeterminate/high-grade carcinoma. In most cases, there were relatively few somatic mutations shared between matched low-grade and higher-grade tumors compared with private mutations specific to each component (ie, phylogenetic trees with short trunks and long branches). Truncal mutations, present across all tumor samples from a given patient, included known drivers of low-grade serous neoplasms: <em>KRAS</em> (G12D, n = 4), <em>BRAF</em> (G469A, n = 1), <em>NF2</em> (n = 1), and <em>USP9X</em> (n = 1). Transformation to HGSC was associated with a <em>TP53</em> mutation with bi-allelic inactivation in 3 cases, all with severe nuclear atypia, and associated with genome-wide copy number alterations and allelic imbalances. <em>TP53</em>-wildtype tumors comprised a morphologic spectrum, which included indeterminate-grade serous carcinomas with moderate nuclear atypia and high mitotic activity, although lacking extensive chromosomal instability (n = 2) and poorly differentiated carcinomas (n = 2, including a high-grade Mullerian carcinoma and an undifferentiated carcinoma with sarcomatoid features). In summary, synchronous and metachronous low-grade serous neoplasms and higher-grade carcinomas are clonally related. Early genetic divergence, most evident in cases with <em>TP53</em> mutations, suggests that high-grade transformation may be a relatively early molecular event.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100629"},"PeriodicalIF":7.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"POU4F3 Is a Sensitive and Specific Marker of Merkel Cell Carcinoma","authors":"Paweł Karpinski ,&nbsp;Javier E. Mendez-Pena ,&nbsp;Cheng-Lin Wu ,&nbsp;Ali Akalin ,&nbsp;Kristine M. Cornejo ,&nbsp;Yin P. Hung ,&nbsp;Mai P. Hoang","doi":"10.1016/j.modpat.2024.100627","DOIUrl":"10.1016/j.modpat.2024.100627","url":null,"abstract":"<div><div>Although of therapeutic importance, a single sensitive and specific immunostain to distinguish Merkel cell carcinoma (MCC) from mimics is not currently available. In addition, single tumor cells are difficult to detect in sentinel lymph node biopsy. Leveraging publicly available data sets of 9264 solid tumors and &gt;600,000 single-cell transcriptomes, we identified <em>POU4F3</em> to be a specific marker of MCC. Analyses of Pan-Cancer RNA bulk sequencing data of 24 tumor types from Tumor Cancer Genomic Atlas data sets as well as non-Tumor Cancer Genomic Atlas small cell lung carcinoma and MCC data sets confirmed <em>POU4F3</em> specificity for MCC. Single-cell RNA-sequencing analyses also confirmed the lack of <em>POU4F3</em> expression in lung small cell carcinoma as well as a variety of normal tissues. Nuclear POU4F3 immunohistochemical expression was noted in 98.7% of 153 MCCs and in only 1.7% of mimics (3 of 180 cases, including 95 small cell carcinomas, of which 55 were from lungs and the remainder from other sites). Three POU4F3-positive non-MCC cases were from lungs (2 cases) and vagina (1 case). All 153 tested MCC cases were negative for ASCL1, a key transcriptional regulator highly expressed in small cell lung carcinoma. NeuroD1 was seen in a subset of MCC cases (20.9%, 32/153). POU4F3 immunostain was performed on 29 sentinel lymph nodes, and strong POU4F3 nuclear expression facilitated the ease of metastasis detection, even single tumor cells. Our study built on prior works shows that POU4F3 is a sensitive and specific clinical marker of MCC.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100627"},"PeriodicalIF":7.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Genomic Study of Conventional and Undifferentiated Melanoma","authors":"Grant M. Fischer,&nbsp;Navin R. Mahadevan,&nbsp;Jason L. Hornick,&nbsp;Christopher D.M. Fletcher,&nbsp;Eleanor Russell-Goldman","doi":"10.1016/j.modpat.2024.100626","DOIUrl":"10.1016/j.modpat.2024.100626","url":null,"abstract":"<div><div>Undifferentiated melanoma, defined as melanoma that has lost all usual phenotypic and immunohistochemical characteristics of conventional melanoma, can pose significant diagnostic challenges. Molecular studies have advanced our understanding of undifferentiated melanoma by demonstrating that a subset of these tumors harbors known melanoma driver alterations in genes such as <em>BRAF</em>, <em>NRAS</em>, and <em>NF1</em>. However, there is a paucity of data describing genetic alterations that may distinguish undifferentiated melanoma from conventional melanoma. In this study, we directly compared the genomic profiles of undifferentiated melanoma to a cohort of conventional melanomas, including 14 undifferentiated melanoma cases (comprised of 2 primary cases, 2 cutaneous recurrences, and 10 metastases) and a cohort of 127 conventional melanomas including primary, recurrent, and metastatic cases. Targeted sequencing of 447 cancer-associated genes was performed, including identification of mutations and copy number alterations. <em>NRAS</em> was the most frequent melanoma driver in undifferentiated melanoma (8/14 cases, 57%), although notably, only 1 undifferentiated melanoma harbored an <em>NRAS</em> Q61R mutation. Compared with the conventional melanoma cohort, undifferentiated melanoma demonstrated statistically significant enrichment of pathogenic activating <em>RAC1</em> mutations (6/14 total cases, 43%), including P29S (4/6 cases), P29L (1/6 cases), and D11E (1/6 cases). In addition to providing insight into the molecular pathogenesis of undifferentiated melanoma, these findings also suggest that RAS Q61R immunohistochemistry may have limited utility for its diagnosis. The presence of recurrent <em>RAC1</em> mutations in undifferentiated melanoma is also notable as these alterations may contribute to mitogen-activated protein kinase pathway–targeted therapy resistance. Furthermore, the <em>RAC1</em> alterations identified in this cohort have been shown to drive a melanocytic to mesenchymal switch in melanocytes, offering a possible explanation for the undifferentiated phenotype of these melanomas.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100626"},"PeriodicalIF":7.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Profiling of Salivary Gland Tumors Supports and Expands Conventional Classification","authors":"Philipp Jurmeister ,&nbsp;Maximilian Leitheiser ,&nbsp;Alexander Arnold ,&nbsp;Emma Payá Capilla ,&nbsp;Liliana H. Mochmann ,&nbsp;Yauheniya Zhdanovic ,&nbsp;Konstanze Schleich ,&nbsp;Nina Jung ,&nbsp;Edgar Calderon Chimal ,&nbsp;Andreas Jung ,&nbsp;Jörg Kumbrink ,&nbsp;Patrick Harter ,&nbsp;Niklas Prenißl ,&nbsp;Sefer Elezkurtaj ,&nbsp;Luka Brcic ,&nbsp;Nikolaus Deigendesch ,&nbsp;Stephan Frank ,&nbsp;Jürgen Hench ,&nbsp;Sebastian Försch ,&nbsp;Gerben Breimer ,&nbsp;Stephan Ihrler","doi":"10.1016/j.modpat.2024.100625","DOIUrl":"10.1016/j.modpat.2024.100625","url":null,"abstract":"<div><div>Tumors of the major and minor salivary glands histologically encompass a diverse and partly overlapping spectrum of frequent diagnostically challenging neoplasms. Despite recent advances in molecular testing and the identification of tumor-specific mutations or gene fusions, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that achieved a mean balanced accuracy of 0.991. Of note, we showed that cribriform adenocarcinoma is epigenetically distinct from classical polymorphous adenocarcinoma, which could support risk stratification of these tumors. Myoepithelioma and pleomorphic adenoma form a uniform epigenetic class, supporting the theory of a single entity with a broad but continuous morphologic spectrum. Furthermore, we identified a histomorphologically heterogeneous but epigenetically distinct class that could represent a novel tumor entity. In conclusion, our study provides a comprehensive resource of the DNA methylation landscape of salivary gland tumors. Our data provide novel insight into disputed entities and show the potential of DNA methylation to identify new tumor classes. Furthermore, in future, our machine learning classifier could support the histopathologic diagnosis of salivary gland tumors.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100625"},"PeriodicalIF":7.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Cancer-Immune Phenotypes Predict Shorter Recurrence-Free Survival in the No Specific Molecular Profile Molecular Subtype of Endometrial Carcinoma","authors":"Dario de Biase ,&nbsp;Jacopo Lenzi ,&nbsp;Claudio Ceccarelli ,&nbsp;Thais Maloberti ,&nbsp;Marco Grillini ,&nbsp;Camelia Alexandra Coadǎ ,&nbsp;Claudio Zamagni ,&nbsp;Pierandrea De Iaco ,&nbsp;Anna Myriam Perrone ,&nbsp;Donatella Santini ,&nbsp;Martin Köbel ,&nbsp;Cheng-Han Lee ,&nbsp;Giovanni Tallini ,&nbsp;Antonio De Leo","doi":"10.1016/j.modpat.2024.100624","DOIUrl":"10.1016/j.modpat.2024.100624","url":null,"abstract":"<div><div>Compartmentation of the immune response into 3 main spatial cancer-immune phenotypes (SCIs) – inflamed, excluded, and desert – has been proposed as the main predictor of response to immune checkpoint inhibitors in solid tumors. The objective of the study was to define and characterize the SCI in a consecutive series of 213 endometrial carcinomas (ECs) by correlating it with molecular subtypes, clinicopathologic features, and prognosis. Immunohistochemistry (IHC) and next-generation sequencing were used to assign surrogate molecular EC subtypes: <em>POLE</em> mutant (<em>POLE</em>), mismatch repair deficient (MMRd), <em>TP53</em> mutant (p53abn), and no specific molecular profile (NSMP). Immune cell markers (CD20, CD3, CD8, CD68, PD-L1) were assessed by IHC on whole sections and quantified by digital image analysis to define the 3 SCIs. ECs were stratified into 4 molecular subtypes: 17 (8.0%) <em>POLE</em>, 68 (31.9%) MMRd, 42 (19.7%) p53abn, and 86 (40.4%) NSMP. SCI determination showed 105 (49.3%) inflamed, 62 (29.1%) desert, and 46 (25.6%) excluded tumors. The inflamed phenotype was more prevalent in MMRd (64.7%) and <em>POLE</em> (76.5%) subtypes compared with NSMP (45.3%) and p53abn (21.4%). SCI revealed a strong correlation with disease-free survival in NSMP tumors: inflamed 96.2%, desert 83.2%, and excluded 40.5%. The SCI prognostic impact was also maintained in NSMP cases treated with adjuvant therapy resulting in a significant difference in recurrence between the inflamed and excluded phenotypes. To simplify SCI determination, a subset of immune cell markers was selected as appropriate to define the 3 SCI patterns: high intraepithelial CD8 for the inflamed phenotype; CD68, CD20, and PD-L1 to discriminate between desert and excluded tumors. The integration of SCI into molecular classification could be a promising opportunity to improve the prognostic risk stratification of patients and may guide the therapeutic approach, particularly in the NSMP subtype. Thus, the different patterns of immune response are a new prognostic parameter in the NSMP subtype.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100624"},"PeriodicalIF":7.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic and Molecular Characterization of IDH-Mutant Prostatic Adenocarcinoma","authors":"Benzion Samueli,&nbsp;Hikmat Al-Ahmadie,&nbsp;Ying-Bei Chen,&nbsp;Anuradha Gopalan,&nbsp;Judy Sarungbam,&nbsp;Satish K. Tickoo,&nbsp;Victor E. Reuter,&nbsp;Samson W. Fine,&nbsp;Jie-Fu Chen","doi":"10.1016/j.modpat.2024.100616","DOIUrl":"10.1016/j.modpat.2024.100616","url":null,"abstract":"<div><div>Gain-of-function isocitrate dehydrogenase (<em>IDH</em>) mutations are pathogenically significant in many tumor types and are actionable in cholangiocarcinoma, low-grade glioma, and acute myeloid leukemia. Rare <em>IDH</em> mutations have been described in prostatic adenocarcinoma (PCa). Recent publications have suggested that psammomatous calcifications in PCa are associated with <em>IDH1</em> mutations. In this retrospective study, we queried our institutional clinical sequencing database (cohort 1), and previously published PCa data sets in cBioPortal (cohort 2). Samples were stratified based on oncogenic hotspot <em>IDH</em> mutations at <em>IDH1</em> R132 and <em>IDH2</em> R140/R172, and other nonhotspot <em>IDH</em> mutations. Seventeen (0.4%) cases were identified from 4033 PCa cases in cohort 1 harboring mutually exclusive oncogenic hotspot <em>IDH1</em> (N = 15, 1 of which was subclonal) or <em>IDH2</em> (N = 2) mutations, and 20 (0.5%) cases had nonhotspot <em>IDH1</em>/<em>2</em> mutations. A histologic review of 13 cases with <em>IDH1</em> hotspot mutations and available material showed grade group 3 or higher disease. Immunohistochemistry was performed on cases with <em>IDH1</em> hotspot mutations when possible and showed AR, PSA, PSMA, and NKX3.1 positive in all the 4 cases stained. In cohort 2, 9 cases (0.3%) harboring <em>IDH1</em> hotspot mutations were identified from 2749 patients, and 9 cases carried nonhotspot <em>IDH1/2</em> mutations. The combined cohorts of 23 PCa cases with clonal <em>IDH1</em> hotspot mutations had no ETS fusions, <em>SPOP</em> hotspot mutations, and somatic or germline alterations in <em>BRCA1/2, ATM, RB1,</em> or <em>AR</em>; 19 cases with successful microsatellite instability testing were all microsatellite stable. Conversely, among 29 cases with nonhotspot <em>IDH</em> mutations, there were 4 with <em>TMPRSS2::ERG</em> fusions, 6 with <em>SPOP</em> hotspot mutations, and 10 with <em>AR</em> amplifications/hotspot mutations; 8 were microsatellite instability high. Notably, two cases with <em>IDH1</em> hotspot mutations had psammomatous calcifications. Our findings provide evidence that <em>IDH1</em> hotspot mutations serve as driver alterations in this rare yet distinct molecular subset of PCa. Further studies are warranted to correlate response to androgen deprivation and IDH inhibitors.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 1","pages":"Article 100616"},"PeriodicalIF":7.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes—Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes (MDS [icMDS])","authors":"Fnu Aakash ,&nbsp;Savanah D. Gisriel ,&nbsp;Amer M. Zeidan ,&nbsp;John M. Bennett ,&nbsp;Rafael Bejar ,&nbsp;Jan Philipp Bewersdorf ,&nbsp;Uma M. Borate ,&nbsp;Jacqueline Boultwood ,&nbsp;Andrew M. Brunner ,&nbsp;Rena Buckstein ,&nbsp;Hetty E. Carraway ,&nbsp;Jane E. Churpek ,&nbsp;Naval G. Daver ,&nbsp;Amy E. DeZern ,&nbsp;Fabio Efficace ,&nbsp;Pierre Fenaux ,&nbsp;Maria E. Figueroa ,&nbsp;Guillermo Garcia-Manero ,&nbsp;Steven D. Gore ,&nbsp;Peter L. Greenberg ,&nbsp;Sanam Loghavi","doi":"10.1016/j.modpat.2024.100615","DOIUrl":"10.1016/j.modpat.2024.100615","url":null,"abstract":"<div><div>Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of biologically distinct entities characterized by variable degrees of ineffective hematopoiesis. Recently, 2 classification systems (the 5th edition of the World Health Organization Classification of Haematolymphoid tTumours and the International Consensus Classification) further subcharacterized MDS into morphologically and genetically defined groups. Accurate diagnosis and subclassification of MDS require a multistep systemic approach. The International Consortium for MDS (icMDS) summarizes a contemporary, practical, and multimodal approach to MDS diagnosis and classification.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100615"},"PeriodicalIF":7.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Sequencing May Call CEP170::RAD51B Fusion Because of Alignment Artifacts","authors":"Cheng Lei ,&nbsp;Peng Zhou ,&nbsp;Yi Sun ,&nbsp;Qingchun Liang","doi":"10.1016/j.modpat.2024.100597","DOIUrl":"10.1016/j.modpat.2024.100597","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 10","pages":"Article 100597"},"PeriodicalIF":7.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Aspects of Artificial Intelligence and Machine Learning","authors":"Liron Pantanowitz ,&nbsp;Matthew Hanna ,&nbsp;Joshua Pantanowitz ,&nbsp;Joe Lennerz ,&nbsp;Walter H. Henricks ,&nbsp;Peter Shen ,&nbsp;Bruce Quinn ,&nbsp;Shannon Bennet ,&nbsp;Hooman H. Rashidi","doi":"10.1016/j.modpat.2024.100609","DOIUrl":"10.1016/j.modpat.2024.100609","url":null,"abstract":"<div><div>In the realm of health care, numerous generative and nongenerative artificial intelligence and machine learning (AI-ML) tools have been developed and deployed. Simultaneously, manufacturers of medical devices are leveraging AI-ML. However, the adoption of AI in health care raises several concerns, including safety, security, ethical biases, accountability, trust, economic impact, and environmental effects. Effective regulation can mitigate some of these risks, promote fairness, establish standards, and advocate for more sustainable AI practices. Regulating AI tools not only ensures their safe and effective adoption but also fosters public trust. It is important that regulations remain flexible to accommodate rapid advances in this field to support innovation and also not to add additional burden to some of our preexisting and well-established frameworks. This study covers regional and global regulatory aspects of AI-ML including data privacy, software as a medical device, agency approval and clearance pathways, reimbursement, and laboratory-developed tests.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100609"},"PeriodicalIF":7.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence—A Retrospective Study in a Longitudinal Cohort","authors":"Yen Chen Kevin Ko ,&nbsp;Kelly Yi Ping Liu ,&nbsp;Esther Chen ,&nbsp;Sarah Yuqi Zhu ,&nbsp;Catherine F. Poh","doi":"10.1016/j.modpat.2024.100613","DOIUrl":"10.1016/j.modpat.2024.100613","url":null,"abstract":"<div><div>Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ). Tissue microarrays were constructed from the most representative area of the pathology. Three consecutive sections were sectioned and stained for hematoxylin and eosin, p53 immunohistochemistry, and p16 immunohistochemistry. The staining results were reviewed by 2 pathologists (Y.C.K.K., C.F.P.) blinded to clinical outcome. Samples were categorized into p53 abnormal OED (n = 46), p53 conventional OED (n = 118), and p53 human papillomavirus (HPV) OED (HPV associated) (n = 12) using a previously published pattern-based approach. All cases of p53 HPV OED (HPV associated) were identified in HGLs. In contrast, cases of p53 abnormal OED were observed in mild OED (9.5%), moderate OED (23%), and severe OED/carcinoma in situ (51%). None of the 27 reactive or nondysplastic lesions showed abnormal p53 staining patterns. Among the 135 low-grade lesions, 23 cases (17.0%; 2 mild OEDs and 21 moderate OEDs) progressed to HGL or squamous cell carcinoma, with 11 cases showing progression within the first 3 years. Remarkably, 82% (9/11) of these faster progressors showed abnormal p53 patterns. Survival analysis revealed that p53 abnormal OED had significantly poorer progression-free probability (<em>P</em> &lt; .0001) with hazard ratio of 11.24 (95% CI, 4.26-29.66) compared with p53 conventional OED. Furthermore, p53 abnormal OED had poorer local recurrence–free survival compared with p53 wild-type OED (<em>P</em> = .03). The study supports that OED with p53 abnormal pattern is at high risk for progression and recurrence independent of the dysplasia grade.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100613"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}