Histopathological Subtypes Research Articles

Dual-energy CT for predicting serosal invasion in gastric cancer and subtype analysis.

To predict the serosal invasion of gastric cancer (GC) using dual-energy CT (DECT)-based parameters and analyze the diagnostic performance according to different subtypes. The patients were divided into the T1-3 group and T4a group. The irregular region of interest (ROI) was manually delineated on the largest cross-section of the lesion. The ROI area, iodine concentration (IC), normalized iodine concentration (nIC), fat fraction, CT value mean, and standard deviation were measured in the late arterial (LAP) and venous phase (VP). The Mann-Whitney U test was used to assess differences between different T-stage groups and histopathological subtypes of GC. A model was established based on DECT parameters, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance. Preliminary analysis showed that there were significant differences in ROI area, IC, nIC and CT value mean in VP and ROI area in LAP between T1-3 and T4a GC (all p < 0.05). The AUC of the comprehensive model composed of ROI and nIC in VP was 0.805. For different subtypes, multiple DECT parameters of poorly cohesive carcinoma (PCC) showed significant differences. ROI area in LAP and VP, IC, nIC, and CT value mean in VP have significant differences in distinguishing between T1-3 and T4a GC. Iodine-related parameters in VP differed significantly between T1-3 and T4a in PCCs, rather than TACs. Considering the heterogeneity of different WHO subtypes, DECT iodine-related parameters in VP are more predictive of the serosal invasion status of GC compared to LAP.

Plasma cell-free DNA chromatin immunoprecipitation profiling depicts phenotypic and clinical heterogeneity in advanced prostate cancer.

Cell phenotype underlies prostate cancer presentation and treatment resistance and can be regulated by epigenomic features. However, the osteotropic tendency of prostate cancer limits access to metastatic tissue, meaning most prior insights into prostate cancer chromatin biology are from preclinical models that do not fully represent disease complexity. Noninvasive chromatin immunoprecipitation of histones in plasma cell-free in humans may enable capture of disparate prostate cancer phenotypes. Here, we analyzed activating promoter- and enhancer-associated H3K4me2 from cfDNA in metastatic prostate cancer enriched for divergent patterns of metastasis and diverse clinical presentation. H3K4me2 density across prostate cancer genes, accessible chromatin, and lineage-defining transcription factor binding sites correlated strongly with circulating tumor DNA (ctDNA) fraction-demonstrating capture of prostate cancer-specific biology and informing the development of a statistical framework to adjust for ctDNA fraction. Chromatin hallmarks mirrored synchronously measured clinico-genomic features: bone versus liver-predominant disease, serum PSA, biopsy-confirmed histopathological subtype, and RB1 deletions convergently indicated phenotype segregation along an axis of differential androgen receptor activity and neuroendocrine identity. Detection of lineage switching after sequential progression on systemic therapy in select patients indicates potential utility for individualized resistance monitoring. Epigenomic footprints of metastasis-induced normal tissue destruction were evident in bulk cfDNA from two patients. Finally, a public epigenomic resource was generated using a distinct chromatin marker that has not been widely investigated in prostate cancer. These results provide insight into the adaptive molecular landscape of aggressive prostate cancer and endorse plasma cfDNA chromatin profiling as a biomarker source and biological discovery tool.

Application of T1-mapping combined with high-spatial-resolution T2-weighted imaging in discriminating mucinous from nonmucinous adenocarcinoma in rectal cancer.

The aim of this study was to evaluate the utility of T1-mapping, high-spatial-resolution T2-weighted imaging (HR-T2WI), and their combined model in distinguishing between adenocarcinoma not otherwise specified (AC) and mucinous adenocarcinoma (MC) in rectal cancer. A total of 55 patients with pathologically confirmed AC and 37 patients with MC were included in the study. Two radiologists independently reviewed the HR-T2WI and provided assessments of histopathological type. Additionally, T1 relaxation times were quantified using whole-tumor volume methods both pre-contrast (T1p) and post-contrast administration (T1e). The absolute reduction in T1 value (T1d) and the percentage reduction (T1d%) were calculated. Receiver operating characteristic curve analysis was performed to evaluate diagnostic efficacy. HR-T2WI demonstrated a sensitivity, specificity, and accuracy of 81.08%, 94.55%, and 89.13%, respectively, in distinguishing rectal MC. T1p, T1e, and T1d values were significantly higher in the MC group compared to the AC group (P < 0.001, = 0.019, and < 0.001, respectively), while there was no statistically significant difference in T1d% between the two groups. Among these quantitative parameters, T1p showed the highest diagnostic efficiency for identifying MC, with a sensitivity of 59.46%, specificity of 92.73%, and moderate diagnostic accuracy (AUC = 0.819). Combining HR-T2WI with T1p (sensitivity = 86.49%, specificity = 92.73, AUC = 0.927) yielded superior performance over single parameters in distinguishing histopathological subtypes. T1p is effective in discriminating between AC and MC in rectal cancer. Importantly, the combined model incorporating HR-T2WI and T1p demonstrated enhanced capability in distinguishing histopathological subtypes of rectal cancer, which benefits individualized treatment.

The value of non-enhanced CT 3D visualization in differentiating stage Ⅰ invasive lung adenocarcinoma between LPA and non-LPA

ObjectiveThis study aims to analyze the quantitative parameters and morphological indices of three-dimensional (3D) visualization to differentiate lepidic predominant adenocarcinoma (LPA) from non-LPA subtypes, which include acinar predominant adenocarcinoma (APA), papillary predominant adenocarcinoma (PPA), micropapillary predominant adenocarcinoma (MPA), and solid predominant adenocarcinoma (SPA). MethodsA group of 178 individuals diagnosed with lung adenocarcinoma were chosen and categorized into two groups: the LPA group and the non-LPA group, according to their pathological results. Quantitative parameters and morphological indexes such as 3D volume, solid proportion, and vascular cluster sign were obtained using 3D visualization and reconstruction techniques. ResultsSignificant differences were observed in the vascular cluster sign, spiculation, shape, air bronchogram, bubble-like lucency, margin, pleural indentation, lobulation, maximum tumor diameter, 3D mean CT value, 3D volume, 3D mass, 3D density, and solid proportion between two groups (P<0.05). The optimal cut-off values for diagnosing non-LPA were a 3D mean CT value of -445.45 HU, a 3D density of 0.56mg·mm-3, and a solid proportion reaching 27.95%. Multivariate logistic regression analysis revealed that 3D mean CT value, lobulation, and margin characteristics independently predicted stageⅠinvasive lung adenocarcinoma. The combination of three indicators significantly improved prediction accuracy (AUC=0.881). ConclusionThe utilization of 3D visualization technology in a systematic approach enables the acquisition of 3D quantitative parameters and morphological indicators of thin-slice CT lesions. These efforts significantly contribute to the identification of histopathological subtypes for stageⅠinvasive lung adenocarcinoma. When integrated with pertinent clinical data, this offers essential guidance for developing various surgical techniques and treatment plans.

Radiology–pathology correlation of hormonal subtypes of breast cancer based on mammography, ultrasound, and PET imaging

BackgroundBreast cancer is one of the most common cancers among the female population globally and a major cause of death due to cancers among women. It has been classified into histopathological, hormonal, and molecular subtypes based on hormone receptor status. Their management involves a multidisciplinary approach depending on these subtypes, TNM staging, tumour size, and site. The purpose of this study was to assess the correlation between ultrasound and mammography characteristics and the maximum standardized uptake value on PET with hormonal subtypes of breast cancer.MethodsIt was a retrospective study from a single-centre data available for 8 months. In this study, 5 hormonal subtypes were considered; Luminal A, Luminal B, Luminal HER2-positive subtype, HER2-enriched subtype, and triple-negative subtype. The morphology of the lesions analysed on mammography and sonography and the SUV max value on PET were considered for analyses. The prediction performance of these features for the hormonal subtypes of breast cancers was then analysed.ResultsLuminal A and B subtypes of breast cancer had indistinct margins with posterior acoustic shadowing on ultrasound. Triple-negative subtypes were well-circumscribed lesions with posterior acoustic enhancement on ultrasound. HER2-positive lesions characteristically had pleomorphic microcalcifications with mixed posterior acoustic features on mammography. On PET, HER2-enriched cases had the highest SUV, and the Luminal A subtype had the lowest SUV.ConclusionAccording to our observations, there are certain typical morphological imaging characteristics for each hormonal subtype of breast cancer. These imaging modalities may help radiologists and clinicians in stratifying their patients for prognostication and better management.

Relationship of Neoadjuvant Chemotherapy Efficacy with Histopathologic Molecular Subtypes in Breast Cancer Patients

Relationship of Neoadjuvant Chemotherapy Efficacy with Histopathologic Molecular Subtypes in Breast Cancer Patients

Case series of pure mucinous breast carcinoma: A rare histopathological subtype

Pure mucinous breast carcinoma (PMBC) is even rarer and accounts for about 2% of all primary breast carcinoma. It is composed entirely of tumour cells with abundant extracellular mucin and without admixing of infiltrating ductal carcinoma. We studied a total of ten cases of Pure Mucinous Breast Carcinoma. Here we describes each case of demographic features and histopathological features of PMBC. The results of immunohistochemistry of Estrogen receptor (ER), Progesterone receptor (PR), Human epidermal growth factor receptor 2(HER-2neu) were also noted in this case series. All the cases were female and above 50 years of age. Out of 10 cases, 6 cases have the tumour’s location on the left side of the breast and 4 cases have the tumour’s location on the right side of the breast. All the cases belong to the lower grading and staging of the tumour. Only one case had positive lymph node status.Hormone receptor status of all the cases has ER &amp; PR positive expression, HER-2neu negative expression and low Ki 67 labelling index. To conclude, PMBC was associated with lower-grade tumours, lower-stage, infrequent lymph node metastasis and luminal type A hormonal receptor status. These favourable findings suggest that PMBC has a better prognosis and may give a better response to hormonal therapy.

NIMG-01. RADIOMIC DATA ANALYSIS WITH ENSEMBLE MACHINE LEARNING TECHNIQUES PREDICT GRADE, HISTOPATHOLOGIC SUBTYPE, AND 1P/19Q CO-DELETION STATUS IN PATIENTS WITH LOW-GRADE GLIOMAS

Abstract Low-grade gliomas (LGGs) are a diverse group of primary brain tumors characterized by their variable prognosis and treatment response. Traditionally, the management of LGGs has relied on histopathological analysis, which sometimes offers limited insight into tumor behavior and treatment outcomes. Recent advances in radiomics have enabled the extraction of detailed quantitative features from routine imaging, providing a non-invasive method to assess tumor characteristics. These radiomic features can capture underlying tumor heterogeneity more comprehensively than conventional methods. Integrating radiomic data with ensemble machine learning techniques offers a promising approach to enhance the prediction of tumor grade, histopathologic subtype, and genetic alterations such as 1p/19q co-deletion status in LGGs, potentially leading to more tailored therapeutic strategies. We combined radiomic-genomic data from 159 magnetic resonance imaging (MRI) scans from the updated LGG-1p19qDeletion dataset (Erickson 2020) and 114 MRI scans from the ReMIND dataset (Juvekar 2024). Expert radiologists performed segmentations. A total of 2446 extracted radiomic features were initially extracted. Feature selection was performed using wrapper- and filter-based techniques with cross-validation. Prediction models were built using machine learning techniques, including random forest and extreme gradient boosting. Using Random Forest, we achieved high accuracy in predicting histopathologic subtype (88.14%, AUC 96.68%) with precision of 87.86% and Dice score of 87.88%. For grade prediction (accuracy 76.19%, AUC 91.84%), precision was 73.91%, and the Dice score was 77.27%. For 1p/19q co-deletion status (accuracy 75.61%, AUC 82.74%), precision was 77.78%, and the Dice score was 73.68%. Our study establishes a robust radiomic workflow to predict tumor grade, histopathologic subtype, and 1p/19q co-deletion status in low-grade gliomas, enhancing diagnostic accuracy and treatment personalization. This methodology can be applied clinically to improve the stratification of treatment plans for low-grade gliomas, potentially leading to effective, personalized therapy options. Using multicentric data potentially improved external validity, something which past research lacked. Future research should focus on validating and deploying this model using observational multicentric study designs.

Frequent Occurrence of High-Risk Basal Cell Carcinoma in Xeroderma Pigmentosum: A Histopathological Insight From an Indian Cohort.

Xeroderma pigmentosum (XP) is a genodermatosis, characterized both by premature aging and significantly increased risk of non-melanoma and melanoma skin cancers at an early age. However, limited literature is available on the common histopathological subtypes of basal cell carcinoma (BCC) in these patients. In this ambispective case series, we recruited patients of XP who had either a currently present skin tumor or previously excised one, provided their histopathological sections were available. Cytogenetic analysis was performed in all the patients. The histopathological findings were recorded by two trained dermatopathologists. Of 22 recruited patients with XP, 12 patients had 41 BCCs, and 23 (56.09%) of them showed a high-risk histopathological subtype. Basosquamous carcinoma (10, 24.39%) was the most frequent high-risk tumor followed by infiltrative variant (7, 17.07%). Mixed-histopathological subtypes were noted in six (14.63%) cases, and all of them had a high-risk component. The low-risk subtypes included nodular (n = 17, 41.46%) and superficial BCC (1, 2.43%). Though a deep dermal involvement was seen in 27 (65.85%) lesions, none showed a perineural invasion or necrosis. Three (7.31%) lesions showed ulceration, while 10 (24.39%) showed presence of pigmentation. A frequent occurrence of high-risk basal cell carcinoma was noted in patients with XP-mandating creation of appropriate treatment and follow-up strategies in these patients.

Surrogate immunohistochemistry markers in adult gliomas – Experience in a tertiary care hospital

Objectives: The recent World Health Organization classification has recommended the usage of surrogate immunohistochemical markers for molecular classification of gliomas. However, only a few studies have attempted to study the expression of the entire panel of markers. The current study was undertaken to study the association of recognized surrogate immunohistochemical markers (isocitrate dehydrogenase 1 [IDH-1], alpha-thalassemia mental retardation X-linked [ATRX] and p53) in different histological lineages and grades of adult gliomas. Materials and Methods: This study was conducted on 118 cases of adult gliomas diagnosed on histopathology over a 2-year duration in a tertiary care hospital. The expression of surrogate immunohistochemistry markers (IDH-1, ATRX, and p53) in these cases was studied. Statistical analysis: Descriptive statistical analysis with the Statistical Package for the Social Science system version 17.0. Results: The frequency of IDH-1 positivity was significantly higher in oligodendrogliomas (OG: 76.5%; oligoastrocytoma: 100%) versus astrocytoma (AS) (grades 2 and 3: 48.1%). It was also significantly higher in diffuse gliomas (grades 2 and 3) versus glioblastomas (64% vs. 16.9%). Among IDH-mutant diffuse gliomas, ATRX loss was significantly higher in AS versus OGs (84.6% vs. 7.7%). P53 overexpression correlated significantly with histological subtype (AS 2,3: 55.6% vs. OG: 5.9%). Conclusions: The surrogate immunohistochemical panel of IDH-1, ATRX, and p53 showed significant association with distinct histopathological subtypes and is helpful in molecular stratification. Cut-offs of ≥ 10% nuclear positivity for p53 and 50% loss of nuclear ATRX expression showed a good correlation.

Prognostic Significance of Microvessel Density and Hypoxic Markers in Canine Osteosarcoma: Insights into Angiogenesis and Tumor Aggressiveness.

Canine osteosarcoma (OSA) is an aggressive and highly malignant tumor of bone with a poor prognosis and it mirrors the disease in humans. Angiogenesis, the formation of new blood vessels, is driven by hypoxia-induced factors such as HIF-1α and VEGF, both of which play a crucial role in tumor growth and metastasis. However, the role of angiogenesis in OSA remains a topic of ongoing debate. This study aimed to investigate the relationship between angiogenesis, measured by intratumoral microvessel density (MVD), hypoxic markers, and clinical outcomes in 28 dogs diagnosed with appendicular OSA. Clinicopathological data such as age, breed distribution, tumor localization, histopathological subtypes, and metastatic behavior were consistent with reported epidemiologic characteristics of canine OSA, though no significant correlation was found among these variables. The results indicated a significant association between higher MVD and high-grade OSA (p = 0.029), suggesting that increased tumor vascularization is linked to more aggressive tumor behavior. Additionally, elevated VEGF expression was strongly correlated with disease-free interval DFI), with a p-value of 0.045. Although HIF-1α positivity showed a trend towards poorer survival, the results did not reach statistical significance (p = 0.07). These findings highlight the potential role of VEGF as a valuable prognostic marker in canine OSA, which could have potentially important implications for therapeutic targeting and clinical management of the disease. This study advances the understanding of angiogenesis in canine OSA, while emphasizing the need for continued research into the complex mechanisms regulating the interplay between hypoxia, angiogenesis and tumor progression.

CFI-ViT: A coarse-to-fine inference based vision transformer for gastric cancer subtype detection using pathological images

Accurate detection of histopathological cancer subtypes is crucial for personalized treatment. Currently, deep learning methods based on histopathology images have become an effective solution to this problem. However, existing deep learning methods for histopathology image classification often suffer from high computational complexity, not considering the variability of different regions, and failing to synchronize the focus on local–global information effectively. To address these issues, we propose a coarse-to-fine inference based vision transformer (ViT) network (CFI-ViT) for pathological image detection of gastric cancer subtypes. CFI-ViT combines global attention and discriminative and differentiable modules to achieve two-stage inference. In the coarse inference stage, a ViT model with relative position embedding is employed to extract global information from the input images. If the critical information is not sufficiently identified, the differentiable module is adopted to extract local image regions with discrimination for fine-grained screening in the fine inference stage. The effectiveness and superiority of the proposed CFI-ViT method have been validated through three pathological image datasets of gastric cancer, including one private dataset clinically collected from Yunnan Cancer Hospital in China and two publicly available datasets, i.e., HE-GHI-DS and TCGA-STAD. The experimental results demonstrate that CFI-ViT achieves superior recognition accuracy and generalization performance compared to traditional methods, while using only 80 % of the computational resources required by the ViT model.

Changes in Staging and Management of Non-Small Cell Lung Cancer (NSCLC) Patients Following the Implementation of Low-Dose Chest Computed Tomography (LDCT) Screening at Kaohsiung Medical University Hospital.

Low-dose computed tomography (LDCT) has been widely adopted for lung cancer screening due to its proven ability to reduce lung cancer mortality, especially among high-risk populations. This retrospective study aims to evaluate the impact of LDCT screening on non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, following the introduction of LDCT in 2013. The study examines the correlation between LDCT screening volume and changes in the distribution of NSCLC stages, particularly early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, it explores the differences in histopathological subtypes, focusing on adenocarcinoma and squamous cell carcinoma, and assesses the impact of early detection on five-year survival rates. The results show a significant increase in early-stage NSCLC diagnoses, particularly in adenocarcinoma cases, where early-stage diagnoses rose from 10.4% in 2010 to 38.7% in 2019. However, the number of stage IV cases remained stable, indicating that LDCT may not substantially reduce late-stage diagnoses. Pearson's correlation analysis demonstrated a strong positive correlation between LDCT screening and early-stage NSCLC detection, particularly for adenocarcinoma (p < 0.001), though the early detection of squamous cell carcinoma and small cell carcinoma remained limited. The study concludes that LDCT screening plays a crucial role in improving early NSCLC detection and five-year survival rates. Future research should focus on optimizing screening strategies to capture more at-risk populations and enhance the detection of harder-to-diagnose subtypes like squamous cell carcinoma.

Impact of COVID-19 Pandemic on Delay of Melanoma Diagnosis: A Systematic Review and Meta-Analysis.

Several studies have described how the restrictive measures due to COVID-19 have delayed melanoma diagnoses, resulting in an increased rate of more severe cases. Summarizing the sparse results in this context might help to understand the real impact of the COVID-19 pandemic on melanoma. We conducted a systematic review and meta-analysis to investigate how the clinical and prognostic factors of new melanoma diagnoses changed after COVID-19. A literature search in MEDLINE, EMBASE, and Scopus was conducted in September 2023. We included studies published in peer-reviewed journals reporting histopathological data on new diagnoses of cutaneous melanoma in adult patients during and/or after the lockdown compared to those diagnosed before the COVID-19 pandemic. A meta-analysis was conducted utilizing a random effects model. The between-study heterogeneity was assessed via Higgins's I2 statistic. Publication bias was assessed using the Begg and Egger test. This study adhered to the updated PRISMA guidelines. The primary outcome was a comparison of melanoma thickness between the pre-COVID-19 and post-lockdown periods. The secondary outcomes were evaluations of the histopathological subtype, stage, and presence of ulceration and mitosis in melanomas diagnosed in these two pandemic phases. The study included 45 articles. We found a significantly higher proportion of all factors indicating worse prognosis in the post-lockdown period compared to the pre-COVID-19 phase, including high thickness (SOR = 1.14, 95%CI 1.08-1.20 for 1-2 mm; SOR = 1.62, 95%CI 1.08-2.40, for >2 mm), the presence of ulcerations (SOR = 1.35, 95%CI 1.18-1.54), nodular subtype (SOR = 1.19, 95%CI 1.07-1.32), the presence of mitosis (SOR = 1.57, 95% CI 1.17-2.11), and stage III (SOR = 1.39, 95%CI 1.19-1.52) and IV (SOR = 1.44, 95%CI 1.26-1.63). Limitations include the limited studies' geographical distribution and moderate heterogeneity affecting meta-analysis estimates. Our meta-analysis provided evidence of more advanced melanomas diagnosed in the post-COVID-19 pandemic period, emphasizing the importance of creating and updating pandemic preparedness plans to limit the impact of any future events on oncological care.

Prognostic implications across histological subtypes of head and neck squamous cell carcinoma: An update

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide, arising from the mucosal epithelium of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, and sinuses. In addition to the conventional morphologic pattern characterized by the degree of cellular atypia and squamous differentiation, HNSCC is classified into eight histopathologic subtypes: basaloid, spindle cell, adenosquamous, cuniculatum, verrucous, lymphoepithelial, papillary, and acantholytic. MethodsThis review provides a comprehensive review of the literature on the prognostic implications of the histological subtypes of HNSCC. ResultsAlthough there is extensive literature on HNSCC, few studies specifically focus on the treatment and prognosis of its histopathologic subtypes. Among these subtypes, verrucous squamous cell carcinoma and carcinoma cuniculatum generally have a favorable prognosis, while others, such as basaloid and spindle cell squamous cell carcinoma, tend to follow a more aggressive clinical course. ConclusionIn this review, we delve into the histopathological subtypes of HNSCC and explore their clinicopathological, molecular, and prognostic findings. Further molecular investigations aimed at identifying targeted therapies for these subtypes are necessary. Moreover, it is crucial to recognize the emerging histopathological variants documented in the literature, considering the ongoing limitations in prognostic assessment.

Evaluation of Cyclin D1 protein and its association with the clinicopathological characteristics and prognosis of lung cancer: A retrospective study from Southern Kerala, India.

Cyclin D1 is a protein that can enhance the proliferation of cancer cells and has been detected in various malignancies, including lung cancer. However, routine examinations for Cyclin D1 in lung cancer cases have not been conducted in Kerala. This study sought to evaluate the links between cyclin D1 expression, clinicopathological characteristics, and 2-year survival rates in lung cancer. This retrospective cohort study used medical records and paraffin blocks of lung cancer patients at the Regional Cancer Centre in Kerala, India, between 2015 and 2018. The data were collected from 61 subjects, comprising of lung adenocarcinoma (18%), lung squamous cell carcinoma (27.9%), non-small-cell lung carcinoma (18%), poorly differentiated carcinoma (19.7%), and negative for malignant cells (16.4%). Data analysis was conducted using SPSS. The study revealed that 31.10% of the lung cancer patients exhibited overexpression of cyclin D1. A significant correlation was observed between cyclin D1 expression and histopathological results (P = 0.002), indicating that the level of cyclin D1 might be linked to specific histopathological subtypes of lung cancer. Despite this significant finding, cyclin D1 expression did not show any association with the clinical stage of the cancer or other clinical characteristics of the patients. Furthermore, when examining the 2-year survival rates of the patients, the study found no significant difference between those who had overexpression of cyclin D1 and those who did not (P = 0.145). Cyclin D1 expression was associated with histology type of lung cancer with no significant association to prognosis.

Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors

The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms. We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts). The ICI benefit group was enriched for propionate (P=0.01) and butyrate/isobutyrate (P=0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P<0.001, butyrate/isobutyrate P=0.002). The acetyl-CoA pathway (P=0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P=0.07), which was validated in the Routy cohort (P=0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P=0.03), propionic acid (P=0.09), and butyric acid (P=0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P<0.05). Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088). This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).

Potential of PSMA for breast cancer in nuclear medicine: digital quantitative immunohistochemical analysis and implications for a theranostic approach

BackgroundFurther research is still needed to fully understand the potential of prostate-specific membrane antigen (PSMA) in breast cancer (BC) and to develop and optimize targeted therapies and imaging modalities. The objective of this study was to present a comprehensive analysis of immunohistochemistry data on PSMA staining in BC and to discuss its potential value in a theranostic approach.MethodsFifty-eight male and female patients were randomly selected from a retrospective database of patients who underwent surgery for breast cancer between January 2012 and December 2017 and for whom a specimen is available in our tumour library. Immunodetection of PSMA and CD31 was performed on serial slides. The digitized slides were reviewed and analysed by an experienced pathologist. Additionally, the corresponding TIFF images were processed to calculate the percentage of positive neovessels.ResultsEighteen patients (31.6%) had no expression, 29 (50.9%) had PSMA neovascular expression scored as “1”, and 10 (17.5%) had neovascular expression scored as “2”. Digital immunohistochemistry analysis for this last specific group of patients showed a median proportion of positive neovessels equal to 5% (range: 3–19). A multivariable logistic regression demonstrated that the odds of PSMA positivity were 4.55 times higher in non-luminal tumours and decreased by a factor of 0.12 in lobular subtypes. There was no association between sex or the presence of a germline BRCA1/2 mutation and PSMA expression in tumours.ConclusionsOur study highlights generally low neovascular expression of PSMA in specific histopathological subtypes of breast cancer, which will likely hamper the development of an adequate theranostic strategy.Trial registrationThe procedure has been retrospectively registered to the French National Institute for Health Data (N° F20220615153900).

Surgical and oncological outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma : Aretrospective single center experience.

Peritoneal mesothelioma (PM) is arare disease with various histopathological subtypes. For malignant peritoneal mesothelioma and borderline subgroups locoregional therapy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been implemented. The aim of our study was to retrospectively present the outcome after CRS and HIPEC for patients with different subtypes of peritoneal mesothelioma. In total 15patients received CRS and HIPEC due to peritoneal mesothelioma at our tertiary referral hospital between 2013 and 2022. Surgical and oncologic outcomes of 14 of those patients were retrospectively evaluated as one patient was lost to follow-up. The cohort consisted of 9patients with diffuse malignant peritoneal mesothelioma (64.3%), 3patients with multicystic peritoneal mesothelioma (21.4%) and 2patients with well-differentiated peritoneal mesothelioma (14.3%). Complete cytoreduction was possible in 85.7% (n = 12). The major complication rate was 28.6% (n = 4) and the reoperation rate was 14.3% (n = 2). Median follow-up was 55months (standard error, SE 15.0%, 95% confidence interval, CI 25.6-84.4 months). Over this time period 64.3% (n = 9) had no evidence of disease, 21.4% (n = 3) were alive with disease and 14.3% (n = 2) died of peritoneal mesothelioma. The median recurrence-free survival of patients was 13months (SE13.0%, 95% CI 0.0-32.2 months). None of the patients with multicystic peritoneal mesothelioma had evidence of disease at the time of last follow-up. Patients with peritoneal mesothelioma should receive locoregional treatment as good oncological results can be achieved with reasonable postoperative morbidity. Thus, awareness is necessary for this rare but potentially aggressive disease to offer the best medical care.

MENINGIOMA SIZE IS POSITIVELY CORRELATED WITH TUMOR WHO GRADE

Abstract AIMS It is well established that the surgical outcome is poorer in larger meningiomas. Vascular/ neural encasement and bone/dural/vascular invasion complicate surgical resection. Nevertheless, it is also likely that meningiomas will become biologically more aggressive with increasing size and tumor cell burden. To prove this hypothesis we studied radiological features of 316 meningiomas and correlated these features with tumor WHO-grade. METHOD 316 meningioma patients who were operated on and who received pathological diagnoses at one single institution were analyzed. Pathological grading was revised by one single neuropathologist according to WHO 2021 criteria. 123 high-grade (WHO grade 2 and 3) patients were initially selected and later substituted with a further 193 age and anatomical-location-matched individuals. Preoperative MRI studies were analyzed for size, hyperostosis, intratumoral calcification, mass effect, peritumoral edema, shape (globular/en-plaque), lobulation, cystic component, intratumoral heterogeneity, dural tail, and necrosis/hemorrhage. Univariate analysis as well as logistic regression were performed. RESULTS High-grade meningiomas were significantly more common to have lobulation (p: 7.111 x 10-8), necrosis/hemorrhage (p: 1.176 x 10-6), peritumoral edema (p: 3.421 x 10-6), intratumoral heterogeneity (p: 1.201 x 10-5), mass effect (p: 0.0002408), and cystic component (p: 0.003519) compared to WHO grade 1 meningiomas. Logistic regression indicated that tumor volume was an independent and significant parameter. High-grade tumors were significantly larger (40.83 cm3 vs 22.18 cm3, p: 3.518 x 10-6). Skull base meningiomas were of significantly lower grade (p: 0.001318). Mean volume was significantly higher in high-grade meningiomas. Mean tumor volume varied significantly among histopathological subtypes but was highest in anaplastic and atypical subtypes. Tumor volume was strongly correlated with mitosis (p: 2.353 x 10-6), hypercellularity (p: 1.22 x 10-4), spontaneous necrosis (p: 3.273 x 10-4), brain invasion (p: 0.02491), macronucleus (p: 0.05327), small cell (p: 0.09425), and ki-67 levels (p: 2x10-16). CONCLUSION Tumor size is strongly correlated with WHO grade in meningiomas.