Modern Pathology最新文献

{"title":"Multicenter Study on Tumor Budding in Lung Squamous Cell Carcinoma: Comparison Between Biopsy and Resection With Interobserver Variability Assessment","authors":"","doi":"10.1016/j.modpat.2024.100571","DOIUrl":"10.1016/j.modpat.2024.100571","url":null,"abstract":"<div><p>Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphologic feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer, and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, n = 136) and Lausanne (2005-2020, n = 113) with available preoperative biopsies was analyzed for TB and additional histomorphologic parameters, such as spread through airspaces and desmoplasia, by 2 expert pathologists (M.M., C.N.). Results were correlated with clinicopathologic parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm²) in 47.6%, intermediate (5-9 buds/0.785 mm²) in 27.4%, and high (≥10 buds/0.785 mm²) in 25% of cases (median bud count, 5; IQR, 0-26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (<em>P</em> = .192) but significantly different from the score obtained in the biopsy (<em>P</em> &lt; .001). Interobserver variability was moderate, regardless of score location (Cohen kappa, 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (<em>P</em> = .002), presence of lymph node (<em>P</em> = .033), and distant metastases (<em>P</em> = .020), without significant correlation with overall survival, tumor size, or pleural invasion. Desmoplasia was significantly associated with higher PTB (<em>P</em> &lt; .001). Spread through airspaces was present in 34% and associated with lower PTB (<em>P</em> &lt; .001). To conclude, despite confirming TB as a reproducible factor in LUSC, we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final TB score of the resected tumor.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001510/pdfft?md5=436d2a133269a6ef5b07a831d4ca6b68&pid=1-s2.0-S0893395224001510-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748579","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":"Genomic Insights Into High-Grade Infarct-Associated Bone Sarcomas","authors":"","doi":"10.1016/j.modpat.2024.100572","DOIUrl":"10.1016/j.modpat.2024.100572","url":null,"abstract":"<div><p>Sarcomas rarely develop in bones previously compromised by infarcts. These infarct-associated sarcomas often present as undifferentiated pleomorphic sarcomas (UPS), and their genetic characteristics are poorly understood. High-grade UPS of bone are typically treated with a combination of surgery and chemotherapy, similar to osteosarcoma. We conducted a detailed clinicopathologic and genomic analysis of 6 cases of intraosseous sarcomas arising from histologically and radiographically confirmed bone infarcts. We analyzed 523 genes for sequence-level mutations using next-generation sequencing with the TruSight Oncology 500 panel and utilized whole-genome single nucleotide polymorphism Microarray (OncoScan CNV) to detect copy number alterations and loss of heterozygosity (LOH). Genomic instability was assessed through homologous recombination deficiency (HRD) metrics, incorporating LOH, telomeric allelic imbalance, and large-scale state transitions. Fluorescence in situ hybridization and immunohistochemistry validated the findings. The cohort included 3 men and 3 women, with a median age of 70 years, and tumors located in the femur and tibia. Five of the 6 patients developed distant metastases. Treatment involved surgery and chemotherapy or immune checkpoint inhibitors. Genomic analysis revealed significant complexity and high HRD scores, ranging from 32 to 57 (with a cutoff of 32). Chromosome 12 alterations, including segmental amplification or chromothripsis, were observed in 4 cases. Notably, <em>MDM2</em> amplification, confirmed by fluorescence in situ hybridization, was detected in 2 cases. Homozygous deletion of <em>CDKN2A/B</em> was observed in all six cases. Tumor mutational burden levels ranged from 2.4 to 7.9 mutations per megabase. Notable pathogenic mutations included <em>H3-3A</em> mutations (p.G35R and p.G35W), and mutations in <em>HRAS</em>, <em>DNMT3A</em>, <em>NF2</em>, <em>PIK3CA</em>, <em>POLE</em>, and <em>TP53</em>, each in one case. These results suggest that high-grade infarct-associated sarcomas of bone, whereas sharing high levels of structural variations with osteosarcoma, may exhibit potentially less frequent <em>TP53</em> mutations and more common <em>CDKN2A/B</em> deletions. This points to the possibility that the mutation spectrum and disrupted pathways could be distinct from conventional osteosarcoma.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734641","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":"Neuronal Distribution in Colorectal Cancer: Associations With Clinicopathological Parameters and Survival","authors":"","doi":"10.1016/j.modpat.2024.100565","DOIUrl":"10.1016/j.modpat.2024.100565","url":null,"abstract":"<div><p>Over the past years, insights in the cancer neuroscience field increased rapidly, and a potential role for neurons in colorectal carcinogenesis has been recognized. However, knowledge on the neuronal distribution, subtypes, origin, and associations with clinicopathological characteristics in human studies is sparse. In this study, colorectal tumor tissues from the Netherlands Cohort Study on diet and cancer (n = 490) and an in-cohort validation population (n = 529) were immunohistochemically stained for the pan-neuronal markers neurofilament (NF) and protein gene product 9.5 (PGP9.5) to study the association between neuronal marker expression and clinicopathological characteristics. In addition, tumor and healthy colon tissues were stained for neuronal subtype markers, and their immunoreactivity in colorectal cancer (CRC) stroma was analyzed. NF-positive and PGP9.5-positive nerve fibers were found within the tumor stroma and mostly characterized by the neuronal subtype markers vasoactive intestinal peptide and neuronal nitric oxide synthase, suggesting that inhibitory neurons are the most prominent neuronal subtype in CRC. NF and PGP9.5 protein expression were not consistently associated with tumor stage, sublocation, differentiation grade, and median survival. NF immunoreactivity was associated with a worse CRC-specific survival in the study cohort (<em>P</em> = .025) independent of other prognostic factors (hazard ratio, 2.31; 95% CI, 1.33-4.03; <em>P</em> = .003), but these results were not observed in the in-cohort validation group. PGP9.5, in contrast, was associated with a worse CRC-specific survival in the in-cohort validation (<em>P</em> = .046) but not in the study population. This effect disappeared in multivariate analyses (hazard ratio, 0.81; 95% CI, 0.50-1.32; <em>P</em> = .393), indicating that this effect was dependent on other prognostic factors. This study demonstrates that the tumor stroma of CRC patients mainly harbors inhibitory neurons and that NF as a single marker is significantly associated with a poorer CRC-specific survival in the study cohort but necessitates future validation.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001455/pdfft?md5=ebbd21aa57ae2463e20bbd9b1b376da7&pid=1-s2.0-S0893395224001455-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723943","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":"Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma","authors":"","doi":"10.1016/j.modpat.2024.100568","DOIUrl":"10.1016/j.modpat.2024.100568","url":null,"abstract":"<div><p>This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-NEC (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N = 32) or NEC (N = 23) were analyzed using digital spatial profiling (GeoMx DSP, NanoString Technologies). Representative regions of interest were selected from the adenocarcinoma (ADC) portion (ADC-MANEC) and the NEC portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All regions of interest were separated into epithelial components and stromal components using the masking procedure in the GeoMx platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including <em>PEG10</em>, <em>MAP1B</em>, <em>STMN3</em>, and <em>AKT3</em>) and stromal (<em>FN1</em>, <em>COL1A1</em>, <em>SPARC</em>, and <em>BGN</em>) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, whereas fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histologic component of MANEC according to its tumor vs stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation data set for future studies.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727505","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":"Enhancing Prostate Cancer Diagnosis: Artificial intelligence-Driven Virtual Biopsy for Optimal Magnetic Resonance Imaging-Targeted Biopsy Approach and Gleason Grading Strategy","authors":"","doi":"10.1016/j.modpat.2024.100564","DOIUrl":"10.1016/j.modpat.2024.100564","url":null,"abstract":"<div><p>An optimal approach to magnetic resonance imaging fusion targeted prostate biopsy (PBx) remains unclear (number of cores, intercore distance, Gleason grading [GG] principle). The aim of this study was to develop a precise pixel-wise segmentation diagnostic artificial intelligence (AI) algorithm for tumor detection and GG as well as an algorithm for virtual prostate biopsy that are used together to systematically investigate and find an optimal approach to targeted PBx. Pixel-wise AI algorithms for tumor detection and GG were developed using a high-quality, manually annotated data set (slides n = 442) after fast-track annotation transfer into segmentation style. To this end, a virtual biopsy algorithm was developed that can perform random biopsies from tumor regions in whole-mount whole-slide images with predefined parameters. A cohort of 115 radical prostatectomy (RP) patient cases with clinically significant, magnetic resonance imaging-visible tumors (n = 121) was used for systematic studies of the optimal biopsy approach. Three expert genitourinary (GU) pathologists (Y.T., A.P., A.Q.) participated in the validation. The tumor detection algorithm (aware version sensitivity/specificity 0.99/0.90, balanced version 0.97/0.97) and GG algorithm (quadratic kappa range vs pathologists 0.77-0.78) perform on par with expert GU pathologists. In total, 65,340 virtual biopsies were performed to study different biopsy approaches with the following results: (1) 4 biopsy cores is the optimal number for a targeted PBx, (2) cumulative GG strategy is superior to using maximal Gleason score for single cores, (3) controlling for minimal intercore distance does not improve the predictive accuracy for the RP Gleason score, (4) using tertiary Gleason pattern principle (for AI tool) in cumulative GG strategy might allow better predictions of final RP Gleason score. The AI algorithm (based on cumulative GG strategy) predicted the RP Gleason score of the tumor better than 2 of the 3 expert GU pathologists. In this study, using an original approach of virtual prostate biopsy on the real cohort of patient cases, we find the optimal approach to the biopsy procedure and the subsequent GG of a targeted PBx. We publicly release 2 large data sets with associated expert pathologists’ GG and our virtual biopsy algorithm.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001443/pdfft?md5=0f4b4a77b04b588b9e6833ca66915ca0&pid=1-s2.0-S0893395224001443-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727506","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":"Analysis of the Application of Professional Society Screening Guidelines for Colorectal Polyposis Syndromes at a Single Institution","authors":"","doi":"10.1016/j.modpat.2024.100567","DOIUrl":"10.1016/j.modpat.2024.100567","url":null,"abstract":"<div><p>Several professional society guidelines suggest germline genetic testing for colorectal polyposis syndromes in patients with ≥10 lifetime adenomatous polyps. This study evaluated the factors associated with genetic testing decisions and outcomes when germline testing was recommended per guidelines. Surgical archives revealed 145 patients with a recommendation for germline genetic polyposis testing based on guidelines. Demographic data and medical history were collected to examine their association with testing decisions and results. Germline genetic testing was ordered in 90 out of 145 patients and was ordered in younger patients with more lifetime adenomas. Pathogenic alterations were detected in 12 out of 53 patients who completed testing. Younger ages and higher numbers of lifetime adenomas were not associated with the detection of germline genetic alterations. In fact, patients with a pathogenic germline alteration had higher median ages and fewer lifetime adenomas than those without an alteration. Half of the 12 patients with a pathogenic germline mutation were not White non-Hispanic, although White non-Hispanic patients comprised 75.5% of those tested. This study supports the 10 adenomatous polyp threshold for recommending germline genetic polyposis testing, as an alteration was detected in a sizable proportion (&gt;20%) of patients tested. Although a younger age and a higher number of lifetime adenomas were associated with an increased likelihood of ordered tests, no evidence was found to support these additional factors in testing decisions.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723939","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":"Evaluation of Artificial Intelligence-Based Gleason Grading Algorithms “in the Wild”","authors":"","doi":"10.1016/j.modpat.2024.100563","DOIUrl":"10.1016/j.modpat.2024.100563","url":null,"abstract":"<div><p>The biopsy Gleason score is an important prognostic marker for prostate cancer patients. It is, however, subject to substantial variability among pathologists. Artificial intelligence (AI)–based algorithms employing deep learning have shown their ability to match pathologists’ performance in assigning Gleason scores, with the potential to enhance pathologists’ grading accuracy. The performance of Gleason AI algorithms in research is mostly reported on common benchmark data sets or within public challenges. In contrast, many commercial algorithms are evaluated in clinical studies, for which data are not publicly released. As commercial AI vendors typically do not publish performance on public benchmarks, comparison between research and commercial AI is difficult. The aims of this study are to evaluate and compare the performance of top-ranked public and commercial algorithms using real-world data. We curated a diverse data set of whole-slide prostate biopsy images through crowdsourcing containing images with a range of Gleason scores and from diverse sources. Predictions were obtained from 5 top-ranked public algorithms from the Prostate cANcer graDe Assessment (PANDA) challenge and 2 commercial Gleason grading algorithms. Additionally, 10 pathologists (A.C., C.R., J.v.I., K.R.M.L., P.R., P.G.S., R.G., S.F.K.J., T.v.d.K., X.F.) evaluated the data set in a reader study. Overall, the pairwise quadratic weighted kappa among pathologists ranged from 0.777 to 0.916. Both public and commercial algorithms showed high agreement with pathologists, with quadratic kappa ranging from 0.617 to 0.900. Commercial algorithms performed on par or outperformed top public algorithms.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001431/pdfft?md5=a7bc615d50d52e0c3a0d705eed9aa9d5&pid=1-s2.0-S0893395224001431-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723942","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":"Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease–Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms","authors":"","doi":"10.1016/j.modpat.2024.100566","DOIUrl":"10.1016/j.modpat.2024.100566","url":null,"abstract":"<div><p>The pathogenesis of neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) in the gastrointestinal tract remains poorly understood. This study aims to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared with a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation. Both groups exhibited a male predominance and similar age distribution. The NEC/MiNEN group was more likely to have a higher percentage of Crohn disease (9/18 vs 1/12; <em>P</em> = .024), occur in the rectum (9/18 vs 3/12) and small intestine (4/18 vs 0/12) (<em>P</em> &lt; .01), be diagnosed on resection without a preceding biopsy (6/18 vs 0/12; <em>P</em> = .057), and have unidentifiable precursor lesions (10/18 vs 1/12; <em>P</em> = .018) than the control group. Synchronous carcinoma, advanced tumor stage (pT3 and pT4), and lymph node metastasis occurred at similar rates; however, the NEC/MiNEN group had a higher incidence of angiovascular invasion (14/18 vs 4/12; <em>P</em> = .024), distant metastasis (8/18 vs 1/12; <em>P</em> = .049), mortality (8/18 vs 2/12; <em>P</em> = .058), and worse survival (Kaplan–Meier; <em>P</em> = .023) than the control group. All tested cases were mismatch repair proficient. A Ki-67 proliferation index ranged from 25% to 100%. Next-generation sequencing in 11 NEC/MiNEN cases revealed low tumor mutational burdens but complex genetic abnormalities commonly involving <em>TP53</em> (9/11; 82%), <em>FBXW7</em> (4/11; 36%), and <em>APC</em> (3/11; 27%) genes, with the other genetic alterations randomly occurring in 1 or 2 cases. The neuroendocrine component, which shared similar molecular alterations as the nonneuroendocrine component, was subcategorized into intermediate (G3a) and high grade (G3b); the higher grade correlated with more genetic alterations. In conclusion, IBD-associated NEC/MiNEN shows diverse histologic features, variable precursor lesions, intricate genetic abnormalities, and aggressive biologic behavior. The classification and grading of gastrointestinal NEC/MiNEN may be refined for better clinical management.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723940","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":"E-Cadherin Mutational Landscape and Outcomes in Breast Invasive Lobular Carcinoma","authors":"","doi":"10.1016/j.modpat.2024.100570","DOIUrl":"10.1016/j.modpat.2024.100570","url":null,"abstract":"<div><p>Invasive lobular carcinomas (ILC) are characterized by the loss of E-cadherin expression and <em>CDH1</em> gene inactivation. Diagnostic reproducibility for this tumor type is currently suboptimal and could be improved by a better understanding of its histomolecular and clinical heterogeneity. We have analyzed the relationship between the presence, type, or position of <em>CDH1</em> mutations, E-cadherin expression, and clinicopathological features (including outcome) in a retrospective series of 251 primary ILC with a long follow-up (median: 9.5 years). The mutational status of E-cadherin gene (<em>CDH1</em>) was determined by RNA sequencing from frozen tumor samples. E-cadherin immunohistochemistry (IHC) was performed with antibodies directed against the intracellular domain (clone 4A2C7) and the extracellular domain (clone NCH38). IHC expression of p120 and β-catenin was also assessed in E-cadherin diffusely positive cases. Three major patterns of E-cadherin membrane expression were identified by IHC, with good agreement between the 2 clones (overall concordance: 83.8%, Kappa 0.67): null/focal expression (≤10%) (72.8% of cases for 4A2C7 and 83.8% for NCH38), heterogeneous expression (11%-89%) (19.2% of cases for 4A2C7 and 6.9% for NCH38), and diffuse expression (≥90%) (8% of cases for 4A2C7 and 9.3% for NCH38). E-cadherin membranous expression, when present, was abnormal (incomplete labeling and/or reduced intensity). ILC with diffuse E-cadherin expression showed abnormal β-catenin or p120-catenin staining in 21% of cases. Interestingly, these cases with diffusely expressed E-cadherin had a <em>CDH1</em> mutation rate as high as the E-cadherin null/focal cases (∼70%) but were enriched in nontruncating mutations. Regarding <em>CDH1</em> mutation location, intracytoplasmic domain mutations correlated with a divergent E-cadherin IHC phenotype between the 2 antibodies (4A2C7 ≤ 10%/NCH38 ≥ 10%). Clinico-pathological correlation analyses found that stromal amount (inversely correlated with tumor cellularity) and tumor-infiltrating lymphocytes were less abundant in ILC with E-cadherin null/focal cases. In addition, <em>CDH1</em> truncating mutations were associated with radiohistologic size discordance and were identified in multivariate survival analysis as an independent poor prognosis factor in terms of metastasis risk and breast cancer-related mortality. Overall, our study highlights the importance of the precise mutational status of <em>CDH1</em> in the clinical, radiological, histologic, and phenotypic expression of lobular carcinomas. These findings should be taken into account in future attempts to improve diagnostic criteria or methods for ILC, as well as for clinicobiological studies dedicated to this tumor type.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001509/pdfft?md5=68672c12c76099957e130ddaff06c0a1&pid=1-s2.0-S0893395224001509-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723941","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":"Novel Artificial Intelligence Combining Convolutional Neural Network and Support Vector Machine to Predict Colorectal Cancer Prognosis and Mutational Signatures From Hematoxylin and Eosin Images","authors":"","doi":"10.1016/j.modpat.2024.100562","DOIUrl":"10.1016/j.modpat.2024.100562","url":null,"abstract":"<div><p>Reducing recurrence following radical resection of colon cancer without overtreatment or undertreatment remains a challenge. Postoperative adjuvant chemotherapy (Adj) is currently administered based solely on pathologic TNM stage. However, prognosis can vary significantly among patients with the same disease stage. Therefore, novel classification systems in addition to the TNM are necessary to inform decision-making regarding postoperative treatment strategies, especially stage II and III disease, and minimize overtreatment and undertreatment with Adj. We developed a prognostic prediction system for colorectal cancer using a combined convolutional neural network and support vector machine approach to extract features from hematoxylin and eosin staining images. We combined the TNM and our artificial intelligence (AI)–based classification system into a modified TNM-AI classification system with high discriminative power for recurrence-free survival. Furthermore, the cancer cell population recognized by this system as low risk of recurrence exhibited the mutational signature SBS87 as a genetic phenotype. The novel AI-based classification system developed here is expected to play an important role in prognostic prediction and personalized treatment selection in oncology.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089339522400142X/pdfft?md5=011a6be48e3b6400ca253fe1b212ac73&pid=1-s2.0-S089339522400142X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633939","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}