Ki67 Index Correlates with Tumoral Volumetry and 5-ALA Residual Fluorescence in Glioblastoma.

BACKGROUND: Malignant gliomas are the most prevalent primary malignant cerebral tumors. Preoperative imaging plays an important role, and the prognosis is closely related to surgical resection and histomolecular aspects. Our goal was to correlate Ki67 indexes with tumoral volumetry in semiautomatic segmentation on preoperative magnetic resonance images and residual fluorescence in a 5-ALA-assisted resection cohort. METHODS: We included eighty-six IDH-wildtype glioblastoma patients with complete preoperative imaging submitted to 5-ALA assisted resections. Clinical, surgical, and histomolecular findings were also obtained. Preoperative magnetic resonance studies were preprocessed and segmented semiautomatically on VISVA for whole tumor (WT) on 3D FLAIR, enhancing tumor (ET), and necrotic core (NC) on 3D post-gadolinium T1. We performed a linear regression analysis for Ki67 and a multivariate analysis for surgical outcomes. RESULTS: Higher Ki-67 indexes correlated positively with higher WT (p = 0.048) ET (p = 0.002). Lower Ki67 correlated with 5-ALA free margins (p = 0.045). WT and ET volumes correlated with the extent of resection (EOR; p = 0.002 and 0.002, respectively). Eloquence did not impact EOR (p = 0.14). CONCLUSIONS: There is a correlation between Ki67, the metabolically active tumoral volumes (WT and ET), and 5-ALA residual fluorescence. Methodological inconsistencies are probably responsible for contradictory literature findings, and further prospective studies are needed to validate and reproduce these findings.

Revolutionizing breast cancer Ki-67 diagnosis: ultrasound radiomics and fully connected neural networks (FCNN) combination method.

PURPOSE: This study aims to assess the diagnostic value of ultrasound habitat sub-region radiomics feature parameters using a fully connected neural networks (FCNN) combination method L2,1-norm in relation to breast cancer Ki-67 status. METHODS: Ultrasound images from 528 cases of female breast cancer at the Affiliated Hospital of Xiangnan University and 232 cases of female breast cancer at the Affiliated Rehabilitation Hospital of Xiangnan University were selected for this study. We utilized deep learning methods to automatically outline the gross tumor volume and perform habitat clustering. Subsequently, habitat sub-regions were extracted to identify radiomics features and underwent feature engineering using the L1,2-norm. A prediction model for the Ki-67 status of breast cancer patients was then developed using a FCNN. The model's performance was evaluated using accuracy, area under the curve (AUC), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), Recall, and F1. In addition, calibration curves and clinical decision curves were plotted for the test set to visually assess the predictive accuracy and clinical benefit of the models. RESULT: Based on the feature engineering using the L1,2-norm, a total of 9 core features were identified. The predictive model, constructed by the FCNN model based on these 9 features, achieved the following scores: ACC 0.856, AUC 0.915, Spe 0.843, PPV 0.920, NPV 0.747, Recall 0.974, and F1 0.890. Furthermore, calibration curves and clinical decision curves of the validation set demonstrated a high level of confidence in the model's performance and its clinical benefit. CONCLUSION: Habitat clustering of ultrasound images of breast cancer is effectively supported by the combined implementation of the L1,2-norm and FCNN algorithms, allowing for the accurate classification of the Ki-67 status in breast cancer patients.

Taurine Improved Autism-Like Behaviours and Defective Neurogenesis of the Hippocampus in BTBR Mice through the PTEN/mTOR/AKT Signalling Pathway.

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.

Noninvasive assessment of Ki-67 labeling index in glioma patients based on multi-parameters derived from advanced MR imaging.

Purpose: To investigate the predictive value of multi-parameters derived from advanced MR imaging for Ki-67 labeling index (LI) in glioma patients. Materials and Methods: One hundred and nine patients with histologically confirmed gliomas were evaluated retrospectively. These patients underwent advanced MR imaging, including dynamic susceptibility-weighted contrast enhanced MR imaging (DSC), MR spectroscopy imaging (MRS), diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI), before treatment. Twenty-one parameters were extracted, including the maximum, minimum and mean values of relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transit time (rMTT), relative apparent diffusion coefficient (rADC), relative fractional anisotropy (rFA) and relative mean diffusivity (rMD) respectively, and ration of choline (Cho)/creatine (Cr), Cho/N-acetylaspartate (NAA) and NAA/Cr. Stepwise multivariate regression was performed to build multivariate models to predict Ki-67 LI. Pearson correlation analysis was used to investigate the correlation between imaging parameters and the grade of glioma. One-way analysis of variance (ANOVA) was used to explore the differences of the imaging parameters among the gliomas of grade II, III, and IV. Results: The multivariate regression showed that the model of five parameters, including rCBVmax (RC=0.282), rCBFmax (RC=0.151), rADCmin (RC= -0.14), rFAmax (RC=0.325) and Cho/Cr ratio (RC=0.157) predicted the Ki-67 LI with a root mean square (RMS) error of 0. 0679 (R2 = 0.8025).The regression check of this model showed that there were no multicollinearity problem (variance inflation factor: rCBVmax, 3.22; rCBFmax, 3.14; rADCmin, 1.96; rFAmax, 2.51; Cho/Cr ratio, 1.64), and the functional form of this model was appropriate (F test: p=0.682). The results of Pearson correlation analysis showed that the rCBVmax, rCBFmax, rFAmax, the ratio of Cho/Cr and Cho/NAA were positively correlated with Ki-67 LI and the grade of glioma, while the rADCmin and rMDmin were negatively correlated with Ki-67 LI and the grade of glioma. Conclusion: Combining multiple parameters derived from DSC, DTI, DWI and MRS can precisely predict the Ki-67 LI in glioma patients.

Prognostic predictive value of Ki-67 in stage I-II triple-negative breast cancer.

Aim: Our research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67. Materials & methods: We retrospectively enrolled 1146 patients diagnosed with stage I-II triple-negative breast cancer. Disease-free and overall survival were analyzed using the Kaplan-Meier method and the Cox regression model. Results: We classified Ki-67 >45% as the high group (n = 716). A Ki-67 level of >45% was associated with poorer disease-free survival (p = 0.039) and overall survival (p = 0.029). Lymph node stage, neoadjuvant chemotherapy, and radiotherapy were independent predictive variables of prognosis. Conclusion: Triple-negative breast cancer may be further subcategorized according to the Ki-67 level. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis of early triple-negative breast cancer.

This study aimed to find the best value of Ki-67, which is a marker used in breast cancer. At last, according to the Ki-67 level over 45%, triple-negative breast cancer may be divided into two groups. Based on the level of Ki-67, treatment decisions may be better. However, we still need more studies to confirm this.

Triple-negative breast cancer may be further subcategorized according to the Ki-67 level >45%, which is associated with a poorer prognosis. Treatment decisions based on the level of Ki-67 may be more favorable to the prognosis of patients.

A novel strategy for predicting the efficacy of temozolomide treatment for metastatic pheochromocytomas/paragangliomas.

BACKGROUND: There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which MPP patients may benefit from TMZ treatment. METHODS: This was a prospective study. MPP patients were enrolled. Patients were treated with TMZ until disease progression or intolerable toxicities. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints included biochemical response rate progression-free survival (PFS) and safety. We compared the difference between effective and ineffective groups, to explore which patients are more suitable for TMZ treatment. RESULTS: 62 patients with MPP were enrolled and tumor response were evaluated in 54 patients. The DCR was 83% (35/42), and the ORR was 24% (10/41) among the progressive patients. PFS was 25.2 ± 3.1 months. The most common adverse event was nausea (41/55). We found that 92.9% (13/14) of patients with MGMT methylation greater than 7% respond to treatment. For the patients with MGMT methylation less than 7%, Ki-67 index could be used to guide the use of TMZ in these patients. Among the patients with Ki-67 index less than 5%, 66% (8/12) patients showed respond to treatment, and only 33% (4/12) patients with Ki-67 index more than 5% showed respond to TMZ. CONCLUSIONS: This study indicated that TMZ is a potential choice for the treatment of MPP with the high ability on disease control and well tolerability. We recommended to MGMT methylation analysis test and Ki-67 index to guide TMZ application.

The value of the malignant subregion-based texture analysis in predicting the Ki-67 status in breast cancer.

Objective: To evaluate the value of the malignant subregion-based texture analysis in predicting Ki-67 status in breast cancer. Materials and methods: The dynamic contrast-enhanced magnetic resonance imaging data of 119 histopathologically confirmed breast cancer patients (81 patients with high Ki-67 expression status) from January 2018 to February 2023 in our hospital were retrospectively collected. According to the enhancement curve of each voxel within the tumor, three subregions were divided: washout subregion, plateau subregion, and persistent subregion. The washout subregion and the plateau subregion were merged as the malignant subregion. The texture features of the malignant subregion were extracted using Pyradiomics software for texture analysis. The differences in texture features were compared between the low and high Ki-67 expression cohorts and then the receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of texture features on Ki-67 expression. Finally, a support vector machine (SVM) classifier was constructed based on differential features to predict the expression level of Ki-67, the performance of the classifier was evaluated using ROC analysis and confirmed using 10-fold cross-validation. Results: Through comparative analysis, 51 features exhibited significant differences between the low and high Ki-67 expression cohorts. Following feature reduction, 5 features were selected to build the SVM classifier, which achieved an area under the ROC curve (AUC) of 0.77 (0.68-0.87) for predicting the Ki-67 expression status. The accuracy, sensitivity, and specificity were 0.76, 0.80, and 0.68, respectively. The average AUC from the 10-fold cross-validation was 0.72 ± 0.14. Conclusion: The texture features of the malignant subregion in breast cancer were potential biomarkers for predicting Ki-67 expression level in breast cancer, which might be used to precisely diagnose and guide the treatment of breast cancer.

Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Nomogram for the preoperative prediction of Ki-67 expression and prognosis in stage IA lung adenocarcinoma based on clinical and multi-slice spiral computed tomography features.

OBJECTIVE: This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram's predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. RESULTS: In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. CONCLUSION: The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.

The REMAR (Rhein-Main-Registry) real-world study: prospective evaluation of the 21-gene breast recurrence score® assay in addition to Ki-67 for adjuvant treatment decisions in early-stage breast cancer.

PURPOSE: Ki-67 is recommended by international/national guidelines for risk stratification in early breast cancer (EBC), particularly for defining "intermediate risk," despite inter-laboratory/inter-observer variability and cutoff uncertainty. We investigated Ki-67 (> 10%- < 40%, determined locally) as a prognostic marker for intermediate/high risk in EBC, pN0-1 patients. METHODS: This prospective, non-interventional, real-world study included females ≥ 18 years, with pN0/pN1mi/pN1, HR+ , HER2-negative EBC, and locally determined Ki-67 ranging 10%-40%. The primary outcome was changes in treatment recommendations after disclosing the Oncotype DX Breast Recurrence Score®(RS) assay result. RESULTS: The analysis included 567 patients (median age, 57 [range, 29-83] years; 70%/1%/29%/ with pN0/pN1mi/pN1 disease; 81% and 19% with RS results 0-25 and 26-100, respectively). The correlations between local and central Ki-67, local Ki-67, and the RS, and central Ki-67 and the RS results were weak (r = 0.35, r = 0.3, and r = 0.46, respectively), and discrepancies were noted in both directions (e.g., local Ki-67 was lower or higher than central Ki-67). After disclosing the RS, treatment recommendations changed for 190 patients (34%). Changes were observed in pN0 and pN1mi/pN1 patients and in patients with centrally determined Ki-67 ≤ 10% and > 10%. Treatment changes were aligned with RS results (adding chemotherapy for patients with higher RS results, omitting it for lower RS results), and their net result was 8% reduction in adjuvant chemotherapy use (from 32% pre-RS results to 24% post-RS results). CONCLUSION: The Oncotype DX® assay is a tool for individualizing treatments that adds to classic treatment decision factors. The RS result and Ki-67 are not interchangeable, and Ki-67, as well as nodal status, should not be used as gatekeepers for testing eligibility, to avoid under and overtreatment.

Image Analysis Using the Fluorescence Imaging of Nuclear Staining (FINS) Algorithm.

Finding appropriate image analysis techniques for a particular purpose can be difficult. In the context of the analysis of immunocytochemistry images, where the key information lies in the number of nuclei containing co-localised fluorescent signals from a marker of interest, researchers often opt to use manual counting techniques because of the paucity of available tools. Here, we present the development and validation of the Fluorescence Imaging of Nuclear Staining (FINS) algorithm for the quantification of fluorescent signals from immunocytochemically stained cells. The FINS algorithm is based on a variational segmentation of the nuclear stain channel and an iterative thresholding procedure to count co-localised fluorescent signals from nuclear proteins in other channels. We present experimental results comparing the FINS algorithm to the manual counts of seven researchers across a dataset of three human primary cell types which are immunocytochemically stained for a nuclear marker (DAPI), a biomarker of cellular proliferation (Ki67), and a biomarker of DNA damage (γH2AX). The quantitative performance of the algorithm is analysed in terms of consistency with the manual count data and acquisition time. The FINS algorithm produces data consistent with that achieved by manual counting but improves the process by reducing subjectivity and time. The algorithm is simple to use, based on software that is omnipresent in academia, and allows data review with its simple, intuitive user interface. We hope that, as the FINS tool is open-source and is custom-built for this specific application, it will streamline the analysis of immunocytochemical images.

Comparative Study of Ki-67 Labeling Index Quantification by Eye-rolling, Manual Count, and Digital Image Analysis; An Approach with Caution.

Background and Objective: An accurate Ki-67 labeling index assessment is critical for managing a few tumors, like breast carcinomas and neuroendocrine tumors. We aimed to determine the degree of agreement between digital image analysis (DIA) and eye-rolling assessment (EE) and DIA and manual count (MC) for Ki-67 LI scoring. Methods: A total of 120 cases (both tru-cut biopsies and resected specimens) were selected during the study period from the institutional database, wherein the Ki-67 labeling index was performed. The selected cases were divided into two groups, i.e., breast neoplasms and other neoplasms. The correlation between DIA and EE and DIA and MC for Ki-67 LI scoring was calculated in both groups. Results: A total of 113 cases were analyzed for Ki-67 LI by three different methods (EE, MC, and DIA); 7 cases were rejected due to poor image quality. Ki-67 LI scoring by DIA and EE was highly correlated in both study groups with a Spearman's rank correlation coefficient of 0.809 (P=0.01) and 0.904 (P=0.01), respectively. Correlation between DIA and MC methods was also found to be almost perfect in both study groups with a Spearman's rank correlation coefficient of 0.974 (P=0.01) and 0.955 (P=0.01), respectively. Conclusion: ImmunoRatio is a free web-based digital image analysis application that can be used for Ki-67 LI assessment with considerable reliability and reproducibility. Yet, it carries a few limitations and demands a careful approach and final confirmation by an expert.

Effective Ki-67 Reduction by Pre-Surgery Short-Term Administration of Letrozole in (Hormone-Positive) Breast Cancer.

Background & Objective: Antigen Ki-67 (histone-based nuclear protein) is a static marker of tumor cell proliferation and growth and is commonly measured to indicate the effect of treatment in breast cancer patients. This single-arm trial study aimed to evaluate the effect of short-term endocrine therapy (letrozole) on Ki-67 levels in menopausal women with early hormone-positive breast cancer who were referred to two university hospitals. Methods: Patients with a pre-treatment Ki67 of 5% or less were excluded from the study. Participants (n=25) received oral letrozole (2.5 mg daily) seven days before surgery. Ki-67% on both biopsies and the surgical specimens were measured and compared. Results and Conclusion: The mean age of patients was 62±9.4 (48-83 years). Our result indicated that pre-surgery consumption of letrozole for hormone-positive breast cancer can significantly decrease the of Ki-67 labeling index (23.24±9.74 vs. 16.92±9.55, P=0.001 by paired t-test), with no drug-related adverse events.

Nottingham prognostic x (NPx): a risk stratification tool in ER-positive HER2-negative breast cancer: a validation study.

AIMS: In this study, we validate the use of Nottingham Prognostic x (NPx), consisting of tumour size, tumour grade, progesterone receptor (PR) and Ki67 in luminal BC. MATERIALS AND METHODS: Two large cohorts of luminal early-stage BC (n = 2864) were included. PR and Ki67 expression were assessed using full-face resection samples using immunohistochemistry. NPx was calculated and correlated with clinical variables and outcome, together with Oncotype DX recurrence score (RS), that is frequently used as a risk stratifier in luminal BC. RESULTS: In the whole cohort, 38% of patients were classified as high risk using NPx which showed significant association with parameters characteristics of aggressive tumour behaviour and shorter survival (P < 0.0001). NPx classified the moderate Nottingham Prognostic Index (NPI) risk group (n = 1812) into two distinct prognostic subgroups. Of the 82% low-risk group, only 3.8% developed events. Contrasting this, 14% of the high-risk patients developed events during follow-up. A strong association was observed between NPx and Oncotype Dx RS (P < 0.0001), where 66% of patients with intermediate risk RS who had subsequent distant metastases also had a high-risk NPx. CONCLUSION: NPx is a reliable prognostic index in patients with luminal early-stage BC, and in selected patients may be used to guide adjuvant chemotherapy recommendations.

Effect of fenugreek oil on healing of experimentally induced buccal mucosal ulcer by immunohistochemical evaluation of Ki-67 expression.

Wound healing involves multiple populations of cells, the extracellular matrix, and soluble mediators' actions like growth factors and cytokines. Wound care was the target of many research, utilizing new therapy techniques and the progression of acute and chronic wound treatments with techniques involving plants to improve healing and decrease the side effects of drugs. When fenugreek is applied to an ulcer, its anti-inflammatory components are released, reducing unnecessary inflammation and accelerating the healing process. Healing is controlled by growth factors that naturally activate and boost the proliferation of cells, such as Ki-67, which is associated with the growth fraction and represents the cell's ability to proliferate. The current study aims to assess the expression of Ki-67 in rat mucosal ulcers treated with fenugreek leave oil. Twenty-four male Wistar albino rats of 350-450 gm weight were used. The rats were grouped as follows; normal group (normal tissue without ulcer induction), control group (tissue with surgical ulcer induction on the right side), and study group (ulcer treated with fenugreek leave oil on the left side), and had been sacrificed at 3- and 7-day healing durations. Thereafter, the tissue specimens were used for immunohistochemical analysis of Ki-67. The obtained outcomes showed that expression of Ki-67 increased in groups where ulcers were induced, with significant differences between control and study groups on the 3rd day. It was concluded that the application of fenugreek oil had an accelerating effect on the healing process of mucosal ulcers, as indicated by the elevated expression level of Ki-67.

Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.

Qualitative and quantitative MRI analysis of alveolar soft part sarcoma: correlation with histological grade and Ki-67 expression.

OBJECTIVE: To investigate the correlation between MRI findings and histological features for preoperative prediction of histological grading and Ki-67 expression level in alveolar soft part sarcoma (ASPS). METHODS: A retrospective analysis was conducted on 63 ASPS patients (Jan 2017-May 2023). All patients underwent 3.0-T MRI examinations, including conventional sequences, dynamic contrast-enhanced scans with time-intensity curve analysis, and diffusion-weighted imaging with apparent diffusion coefficient (ADC) measurements. Patients were divided into low-grade (histological Grade I) and high-grade (histological Grade II/III) groups based on pathology. Immunohistochemistry was used to assess Ki-67 expression levels in ASPS. Statistical analysis included chi-square tests, Wilcoxon rank-sum test, binary logistic regression analysis, Spearman correlation analysis, and receiver operating characteristic curve analysis of various observational data. RESULTS: There were 29 low-grade and 34 high-grade patients (26 males and 37 females) and a wide age range (5-68 years). Distant metastasis, tumor enhancement characteristics, and ADC values were independent predictors of high-grade ASPS. High-grade ASPS had lower ADC values (p = 0.002), with an area under the curve (AUC), sensitivity, and specificity of 0.723, 79.4%, and 58.6%, respectively, for high-grade prediction. There was a negative correlation between ADC values and Ki-67 expression (r = -0.526; p < 0.001). When the cut-off value of ADC was 0.997 × 10-3 mm²/s, the AUC, sensitivity, and specificity for predicting high Ki-67 expression were 0.805, 65.6%, and 83.9%, respectively. CONCLUSION: Qualitative and quantitative MRI parameters are valuable for predicting histological grading and Ki-67 expression levels in ASPS. CRITICAL RELEVANCE STATEMENT: This study will help provide a more nuanced understanding of ASPS and guide personalized treatment strategies. KEY POINTS: There is limited research on assessing ASPS prognosis through MRI. Metastasis, enhancement, and ADC correlated with histological grade; ADC related to Ki-67 expression. MRI provides clinicians with valuable information on ASPS grading and proliferation activity.

CENPF May Act as a Novel Marker and Highlight the Influence of Pericyte in Infantile Hemangioma.

Infantile hemangioma (IH), a benign microvascular tumor, is marked by early and extensive proliferation of immature hemangioma endothelial cells (Hem-ECs) that naturally regress through differentiation into fibroblasts or adipocytes. However, a challenge persists, as the unique biological behavior of IH remains elusive, despite its general sensitivity to propranolol treatment. Recent evidence suggests that abnormal volume proliferation in IH is primarily attributed to the accumulation of hemangioma pericytes (Hem-Pericytes), in addition to Hem-ECs. Centromere protein F (CENPF) is involved in regulating mitotic processes and has been associated with malignant tumor cell proliferation. It is a key player in maintaining genomic stability during cell division. Our findings revealed specific expression of CENPF in Hem-Pericytes, with a proliferation index (PI) approximately half that of Ki67 (3.28 vs 6.97%) during the proliferative phase of IH. This index decreased rapidly in the involuting phase (P < .05), suggesting that the contribution of pericytes to IH development was comparable to that of Hem-ECs. Tumor expansion and shrinkage may be due to the proliferation, reduction, and differentiation of Hem-Pericytes. In conclusion, we speculate CENPF as a novel marker for clinical pathological diagnosis and a potential therapeutic target, fostering advancements in drug development.

Low FDG uptake in lung metastasis despite high FDG uptake in a primary adenoid cystic carcinoma of a sublingual gland.

Adenoid cystic carcinoma is a rare malignant tumor that primarily occurs in the salivary glands. There are few reports of sublingual gland adenoid cystic carcinoma with lung metastases on which 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed. We report the case of a 57-year-old Japanese woman with an adenoid cystic carcinoma of the sublingual gland with lung metastases in whom the FDG uptake of the lung metastasis was low despite high FDG uptake in the primary lesion. The pathological examination revealed that solid components were more visible and the Ki-67 index was more positive in the primary lesion compared to the metastatic lesion. We speculate that differences in tumor growth ability might have resulted in the differences in FDG uptake. This case demonstrates that significant differences might occur in the FDG uptake between primary and metastatic tumors.

Stem Cell Markers in Neoplasms and their Relationship with Progression-free and Overall Survival in Patients with Recurrence.

BACKGROUND: Gliomas account for 30% of primary brain tumors in adults, and despite the scientific progress in the field, recurrence is prevalent. Glioma Stem Cells (GSCs) can generate tumor cells in vivo and in vitro and they are associated with treatment resistance, tumor progression, and recurrence. Furthermore, the expression of SOX transcription factors (SOX1, SOX2, SOX9) in these cells is responsible for maintaining an oncogenic genotype and is associated with an aggressive tumor phenotype. The relationship between SOX transcription factors and their prognostic role in recurrent gliomas has not been described in detail. Therefore, we set out to describe the relationship between SOX expression and Progression-free Survival (PFS) and Overall Survival (OS) in patients with recurrent gliomas. METHODS: In this observational study, we have retrospectively analyzed 69 patients, of which 20 met the inclusion criteria. The clinical, radiological, and histopathological findings have been described, and survival analysis has been performed according to SOX expression for PFS and OS. RESULTS: We found SOX1, SOX2, and SOX9 to show a non-statistically significant trend with increasing histopathological grade, co-expressed with Ki67, a cell proliferation factor. CONCLUSION: There has been found an inversely proportional correlation between the degree of immunopositivity of SOX1 and OS. A higher SOX1 immunopositivity could predict a worse clinical prognosis. There has also been found an interaction between a pluripotent genotype (GSC) and cell proliferation.