Histological Grade In Patients Research Articles

Pan-Cancer Analysis Identifies BCLAF1 as a Potential Biomarker for Renal Cell Carcinoma.

B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) is a versatile protein involved in the regulation of gene transcription and post-transcriptional processing. Although BCLAF1 exerts a broad tumor suppressor effect or tumor promoter effect in many cancer types, the specific roles concerning its expression levels, and its impact on tumorigenesis in Renal cell carcinoma (RCC) remain unclear. Here, we utilized the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) datasets alongside R software and online tools to unravel the specific roles of BCLAF1 in 33 cancer types, including its expression levels, tumor immune and molecular subtypes, and its correlation with prognosis, diagnosis, DNA methylation, and immune microenvironment. Additionally, we carried out cell biology experiments to independently investigate the expression of BCLAF1 in RCC and its effects on tumor progression. BCLAF1 was differentially expressed in tumor tissues compared to normal tissues across various cancer types and was also differentially expressed in different immune and molecular subtypes. In RCC, patients with high BCLAF1 expression had a better prognosis and BCLAF1 was tightly correlated with the stage, gender, and histological grade of patients. Furthermore, BCLAF1 had higher DNA methylation levels and higher immune infiltration levels in tumor tissues. Additionally, cell functional experiments confirmed the low expression of BCLAF1 in RCC and that BCLAF1 significantly inhibited the proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest in RCC cells in vitro. Our study under-scored the potential of BCLAF1 as an important actor in tumorigenesis, especially concerning RCC where it may serve as an effective prognostic marker.

Exploration of the relationship between tumor-infiltrating lymphocyte score and histological grade in breast cancer

BackgroundThe histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients.MethodsIn this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs.ResultsStatistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648–3.941; P < 0.0001), but TILs-WG is not an independent predictive factor for grade (P > 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3.ConclusionOur results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients.

Oxidative Stress Induced by Chemotherapy: Evaluation of Glutathione and Its Related Antioxidant Enzyme Dynamics in Patients with Colorectal Cancer.

One of the mechanisms of chemotherapy is to increase the oxidative stress of cancer cells, leading to their apoptosis. Glutathione (GSH) and its related antioxidant enzymes might be stimulated to cope with increased oxidative stress during chemotherapy. Here, we studied the fluctuation in oxidative stress and GSH-related antioxidant capacities before tumor resection, after tumor resection, and after resection either with or without chemotherapy in patients with colorectal cancer (CRC). This was a cross-sectional and follow-up design. We followed patients before having tumor resection (pre-resection), one month after tumor resection (post-resection), and after the first scheduled chemotherapy (post-chemo). If patients were required to receive chemotherapy after tumor resection, they were assigned to the chemotherapy group. Eligible patients were scheduled to undergo six to twelve cycles of chemotherapy at 2-week intervals and received single, double, or triple chemotherapeutic drugs as required. Those patients who did not require chemotherapy were assigned to the non-chemotherapy group. Indicators of oxidative stress and GSH-related antioxidant capacities were determined at the above three time points. We found in 48 patients of the chemotherapy group and in 43 patients of the non-chemotherapy group different fluctuations in levels of oxidative stress indicators and GSH-related antioxidant capacities starting from pre-resection, post-resection through the post-chemo period. Both groups showed significantly or slightly increased levels of advanced oxidation protein products (AOPP), GSH, and its related enzymes in tumor tissues compared to adjacent normal tissues. Patients in the chemotherapy group had significantly lower plasma levels of GSH and glutathione disulfide (GSSG), but had significantly higher plasma glutathione peroxidase and glutathione reductase activities than patients in the non-chemotherapy group post-chemo. Plasma levels of malondialdehyde and AOPP were positively or negatively associated with GSH and GSSG levels post-chemo after adjustment for age, sex, and histological grading in patients receiving chemotherapy. These significant associations were, however, not seen in patients without chemotherapy. Patients with CRC may require higher GSH demands to cope with a greater oxidative stress resulting from chemotherapy.

PiRNA-14633 underexpression as an independent prognostic marker in non-small cell lung cancer.

e21223 Background: To determine the expression and function of piRNA-14633 in non-small cell lung cancer (NSCLC) samples were taken from cancer lesions (n = 30) and adjacent normal tissue (n = 30) in NSCLC patients. Methods: piRNA-14633 expression was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effect of piRNA-14633 overexpression was examined in vitro utilizing a human NSCLC cell line H1650 stably transfected with a recombinant lentivirus and compared to empty vector-transfected controls. piRNA-14633 overexpression was verified by RT-PCR. The expression of proteins involved in cell cycle regulation (CDK4) and apoptosis (Bcl-6) and cell migration (MMP-9) in cells was analyzed by Western blot. The effect of piRNA-14633 overexpression on cell viability and proliferation was assessed by an MTT assay cells. Flow cytometric analyses were used to evaluate the effect of piRNA-14633 expression on cell cycle distribution and apoptosis. The migration and invasion potential of piRNA-14633 cells was examined by plating cells in Matrigel-coated chambers. Results: The level of piRNA-14633 expression was found to be significantly lower in NSCLC tissue than normal tissues (P &lt; 0.05). Decreased expression of piRNA-14633 was significantly correlated with lymph node metastasis, clinical stage, and histological grade of patients with NSCLC (P &lt; 0.05). Meanwhile, loss of piRNA-14633 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P &lt; 0.05). The result of biological function shown that H1650 cell-transfected piRNA-14633 had a lower survival fraction, higher percentage of the G0/G1 phases, higher cell apoptosis, significant decrease in migration and invasion, and lower CDK4, Bcl-6, and MMP-9 expression compared with H1650 cell without piRNA-14633 (P &lt; 0.05). Conclusions: Reduced piRNA-14633 expression is associated with increased disease severity, suggesting it is a negative regulator of NSCLC and can serve as a prognostic indicator.

Association of PIWI-interacting RNA-23210 with tumor metastasis in esophageal squamous cell carcinoma.

e16060 Background: his study aimed to analyze the expression, clinical significance of PIWI-interacting RNA-23210 (piRNA-23210) in esophageal squamous cell carcinoma (ESCC) and the biological effect in its cell line by piRNA-23210 overexpression. Methods: Quantitative real-time RT-PCR (qRT-PCR) was used to analyze piRNA-23210 expression in 60 cases of ESCC and 60 cases of normal tissues to study the relationship between piRNA-23210 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress piRNA-23210 and then infect ESCC TE-1 cell line. qRT-PCR was used to detect the level of piRNA-23210. 3-[4,5-dimethylthiazol -2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis, cell cycle, and migration and invasion assays were also conducted as to the influence of the upregulated expression of piRNA-23210 that might be found on TE-1 cells biological effect. Results: The level of piRNA-23210 expression was found to be significantly lower in ESCC tissue than normal tissues (P &lt; 0.05). Decreased expression of piRNA-23210 was significantly correlated with lymph node metastasis, clinic stage, and histological grade of patients with ESCC (P &lt; 0.05). Meanwhile, loss of piRNA-23210 expression correlated significantly with poor overall survival time by Kaplan–Meier analysis (P &lt; 0.05). The result of biological function show that TE-1 cell transfected piRNA-23210 had a lower survival fraction; higher percentage of the G0/G1 phases; higher cell apoptosis; significant decrease in migration and invasion; and lower cyclin D1, Bcl-2, and MMP-7 protein expression compared with TE-1 cell untransfected piRNA-23210 (P &lt; 0.05). Conclusions: piRNA-23210 expression decreased in ESCC and correlated significantly with lymph node metastasis, clinical stage, poor overall survival, cell proliferation, cell cycles, cell apoptosis and migration and invasion in ESCC cell by regulating cyclinD1, Bcl-2, and MMP-7 expression, suggesting that piRNA-23210 may play important roles as a negative regulator to ESCC cell.

GATA-3 expression in breast cancer is related to intratumoral M2 macrophage infiltration and tumor differentiation.

Accumulating evidence indicates that tumor-associated macrophages promote tumor progression and that high macrophage infiltration is correlated with advanced tumor stages and poor prognosis in breast cancer. GATA binding protein 3 (GATA-3) is a differentiation marker related to differentiated states in breast cancer. In this study, we explore how the extent of MI relates to GATA-3 expression, hormonal status, and the differentiation grade of breast cancer. To examine breast cancer in early development, we selected 83 patients that were treated with radical breast-conserving surgery (R0), without lymph node metastases (N0) or distant metastases (M0), with and without postoperative radiotherapy. Immunostaining of M2-macrophage-specific antigen CD163 was used to detect tumor-associated macrophages, and macrophage infiltration was estimated semi-quantitatively into no/low, moderate, and high infiltration. The macrophage infiltration was compared to GATA-3, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression in cancer cells. GATA-3 expression is associated with ER and PR expression but inversely correlated to macrophage infiltration and Nottingham histologic grade. High macrophage infiltration in advanced tumor grade was associated with low GATA-3 expression. The disease-free survival is inversely related to Nottingham histologic grade in patients having tumors with no/low macrophage infiltration, a difference that is not found in patients with moderate/high macrophage infiltration. These findings indicate that macrophage infiltration might impact the differentiation, malignant behavior, and prognosis of breast cancer, regardless of the morphological and hormonal states of the cancer cells in the primary tumor.

Different prognostic role of EGFR mutation according to theIASLC histological grade in patients with resected early-stage lung adenocarcinoma.

The prognostic role of EGFR mutations remains controversial. We aimed to evaluate the prognostic role of EGFR mutation in consideration of the IASLC histological grade in patients with resected early-stage lung adenocarcinoma. A total of 3297 patients with stages I-IIA resected lung adenocarcinoma who had had EGFR mutation tests between January 2014 and December 2019 at the Samsung Medical Center, Seoul, Korea were included. Recurrence-free survival (RFS) was compared by EGFR mutation status (EGFR-M+ versus EGFR-WT) and IASLC histological grade (G1, G2 and G3). Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% confidence intervals (CIs). Compared to the EGFR-WT group, the EGFR-M+ group had a significantly lower proportion of G3 tumour (16 versus 33%, P < 0.001). During a median follow-up of 41.4 months, 376 patients experienced recurrence. After adjusting for histological grade, the aHR for recurrence comparing the EGFR-M+ to the EGFR-WT was 1.30 (95% CI=1.04-1.62, P=0.022). The EGFR-M+ group had a significantly lower 5-year RFS than the EGFR-WT group among G3 patients (58.4 versus 71.5%, P< 0.001), but not among G1 and G2 patients. EGFR mutation status was associated with a risk of recurrence after consideration of the IASLC histological grading, especially in G3 tumours. The results of this study would be useful for developing a new staging system and identifying a subset of patients who may benefit from adjuvant targeted therapy.

Systematic radiomics analysis based on multiparameter MRI to preoperatively predict the expression of Ki67 and histological grade in patients with bladder cancer.

Bladder cancer is among the most prevalent urothelial malignancies. Radiomics-based preoperative prediction of Ki67 and histological grade will facilitate clinical decision-making. This retrospective study recruited 283 bladder cancer patients between 2012 and 2021. Multiparameter MRI sequences included: T1WI, T2WI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging. The radiomics features of intratumoral and peritumoral regions were extracted simultaneously. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithms were employed to select the features. Six machine learning-based classifiers were adopted to construct the radiomics models, and the best was chosen for the model construction. The mRMR and LASSO algorithms were more suitable for Ki67 and histological grade, respectively. Additionally, Ki67 had a higher proportion of intratumoral features, while peritumoral features accounted for a greater proportion of the histological grade. Random forests performed the best in predicting both pathological outcomes. Consequently, the multiparameter MRI (MP-MRI) models achieved area under the curve (AUC) values of 0.977 and 0.852 for Ki67 in training and test sets, respectively, and 0.972 and 0.710 for the histological grade. Radiomics holds the potential to predict multiple pathological outcomes of bladder cancer preoperatively and are expected to provide clinical decision-making guidance. Furthermore, our work inspired the process of radiomics research. This study demonstrated that different feature selection techniques, segmentation regions, classifiers, and MRI sequences will affect the performance of the model. We systematically demonstrated that radiomics can predict histological grade and Ki67.

Development and Validation of an MRI Radiomics-Based Signature to Predict Histological Grade in Patients with Invasive Breast Cancer.

BackgroundHistological grade is an important factor in the overall prognosis of patients with invasive breast cancer. Therefore, the non-invasive assessment of histological grade in breast cancer patients is an increasing concern for clinicians. We aimed to establish an MRI-based radiomics model for preoperative prediction of invasive breast cancer histological grade.MethodsWe enrolled 901 patients with invasive breast cancer and pre-operative MRI. Patients were randomly divided into the training cohort (n=630) and validation cohort (n=271) with a ratio of 7:3. A radiomics signature was constructed by extracting radiomics features from MRI images and was developed according to multivariate logistic regression analysis. The diagnostic performance of the radiomics model was assessed using receiver operating characteristic (ROC) curve analysis.ResultsOf the 901 patients, 618 (68.6%) were histological grade 1 or 2 while 283 (31.4%) were histological grade 3. The area under the ROC curve (AUC) of the radiomics model for the prediction of the histological grade was 0.761 (95% CI 0.728–0.794) in the training cohort and 0.722 (95% CI 0.664–0.777) in the validation cohort. The decision curve analysis (DCA) demonstrated the radiomics model’s clinical application value.ConclusionThis is a preliminary study suggesting that the development of an MRI-based radiomics model can predict the histological grade of invasive breast cancer.

HAEMATOLOGICAL PARAMETERS AND THEIR SIGNIFICANCE IN PREDICTING SEVERITY IN TERMS OF TUMOR GRADE IN PATIENTS WITH ORAL SQUAMOUS CELL CARCINOMA

Objective: The objective of our study was to determine the most reliable haematological parameters for assessing the tumor severity with respect to histological grade in patients with Oral Squamous Cell Carcinoma. Material and Methods: This retrospective cross-sectional study was conducted at Pathology Department, Pakistan Institute of Medical Sciences, Islamabad from January to December 2019. Fifty-eight patients of Oral Squamous Cell Carcinoma were selected by consecutive non-probability sampling. Preoperative hemogram values including total leukocyte count, red cell count, hematocrit, hemoglobin, red cell indices, platelet count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were recorded and was studied how these parameters differed among the histological grades of tumor. Stratification of patients was done based on gender and histological grade of tumor. Independent-sample t-test for gender and ANOVA-test for histological grade was applied to assess differences in haematological parameter measurements between the groups. P&lt; 0.05 was considered significant. Results: Anemia was observed as a common finding in our patients seen in 24% cases. Mean platelet count was within normal range. We observed that the haematological parameters i.e. total leukocyte count, absolute neutrophil count, absolute lymphocyte count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio varied significantly with the advancing grades of the tumor from well-differentiated to poorly-differentiated keratinizing oral squamous cell carcinoma. Conclusion: The pre-surgical haematological profile holds many prognostic indicators, useful in predicting tumor severity in terms of histological differentiation of tumor. Key Words: Oral squamous cell carcinoma, Prognosis, Histology

The utility of diffusion-weighted T2 mapping for the prediction of histological tumor grade in patients with head and neck squamous cell carcinoma.

BackgroundIn head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor histological grade in patients with head and neck squamous cell carcinoma (SCC).MethodsThe cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI).ResultsADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of DW-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82.ConclusionsDW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.

Neutrophil To Lymphocyte Ratio As A Predictor Of Severity In Colorectal Adenocarcinoma.

Colorectal cancers are slowly developing cancers of which more than 95% are adenocarcinomas, beginning in the mucus-producing glands lining the colon and rectum. In Pakistan, colorectal carcinoma is ranked as the seventh most common malignancy in men and the ninth most common in women with a male to female ratio of 9 to 1. This study aimed at investigating Neutrophil to Lymphocyte Ratio (NLR) as a potential marker for predicting severity of disease in terms of tumour histological grade in patients with pre-operative colorectal adenocarcinoma. Retrospective cross-sectional study design was adopted and this study was conducted at the Department of Pathology, Pakistan Institute of Medical Sciences Islamabad. Sixty patients of all age-groups and both genders, diagnosed as colorectal adenocarcinoma on histopathological examination of resected specimens, were selected by consecutive non-probability sampling. Separately, 60 healthy subjects, age and sex-matched, were selected as control. Results revealed that the most common age group was 41-60 years showing 29 cases (48%) followed by the age group 61-80 years with 17 cases (28%). The most common site was the rectum having 24 cases (40%) followed by the right hemicolon with 13 cases (21.7%). The mean of neutrophil to lymphocyte ratio rose in direct proportion to the grade of colorectal carcinoma, showing a mean value of 4.5 in well differentiated low grade carcinoma, 5.0 in moderately differentiated and 6.0 in high grade poorly differentiated carcinoma. All patients had higher total leukocyte count, higher absolute neutrophil count, higher total neutrophil percentage and higher NLR as compared to their normal healthy counterparts. It is concluded that the NLR is directly proportional to tumour grade so it can be used preoperatively to assess whether the tumour is advanced so that it can be dealt with accordingly. This ratio can also be used as an independent screening marker for colorectal carcinoma since it shows very low levels in normal colonic epithelium.

Study on immunoexpression of beta catenin and Ki 67 in oral squamous cell carcinomas

Cancer is a global health problem. It is the third most common cause of death.1 Among the malignant lesions of the oral cavity squamous cell carcinoma represents the most common cancer. It comprises about 90% of oral cancers.2 To elucidate the expression of immunohistochemical localization of β-catenin, To evaluate proliferative index (ki 67) in oral squamous cell cancers. To stusdy the correlation between β-catenin expression, ki 67 expression and tumor differentiation. Comparative case control study. The study was done in Department of Pathology and E.N.T in a tertiary care hospital. 1 year. patients with signs and symptoms of oral squamous cell carcinoma and investigated in a tertiary care hospital setting. A total of 104 (84 Cases and 20 Controls) were included in the study. Biopsy specimens received to pathology department where gross examination of the specimens was done. Aberrant expression of β-catenin in different histological grades is statistically significant. The p-value is .001361. Aberrant expression of β-catenin increased with increase in histological grade. It can be concluded that β-catenin is a significant factor in predicting the histological grade in patients with SCC.

A Novel Clinically Prognostic Stratification Based on Prognostic Nutritional Index Status and Histological Grade in Patients With Gallbladder Cancer After Radical Surgery.

PurposeGallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a 5-year survival rate of 5%. The prognostic models to predict the prognosis of patients with GBC remain controversial. Therefore, to construct a prognosis prediction of GBC, a retrospective cohort study was carried out to investigate the prognostic nutritional index and histological grade in the long-term outcome of patients with GBC after radical surgery (RS).MethodsA retrospective study of a total of 198 patients with GBC who underwent surgical treatment were enrolled. The hematological indicators, imageological data, and perioperative clinical data were acquired for statistical analysis and poor prognosis model construction.ResultsPrognostic nutrition index (PNI) < 45.88, maximum tumor diameter (MTD) > 2.24 cm, and jaundice (JD) were all associated with a poor prognosis in multivariate logistic regression analysis. The prognosis prediction model was based on the three risk factors, which indicated a superior predictive ability in the primary cohort [area under the curve (AUC) = 0.951] and validation cohort (AUC = 0.888). In multivariate Cox regression analysis, poorly differentiation (PD) was associated with poor 3-year survival. In addition, Kaplan–Meier (KM) survival analysis suggested that GBC patients with high-risk scores and PD had a better prognosis after RS (p < 0.05), but there was no significant difference in prognosis for patients with non-poorly differentiation (NPD) or low-risk scores after RS (p > 0.05).ConclusionOur prediction model for GBC patients with prognosis evaluation is accurate and effective. For patients with PD and high-risk scores, RS is highly recommended; a simple cholecystectomy can also be considered for acceptance for patients with NPD or low-risk score. The significant findings provide a new therapeutic strategy for the clinical treatment of GBC.

Diffusion Weighted Imaging in the Assessment of Tumor Grade in Endometrial Cancer Based on Intravoxel Incoherent Motion MRI.

The aim of this study is to investigate the possibility of predicting histological grade in patients with endometrial cancer on the basis of intravoxel incoherent motion (IVIM)-related histogram analysis parameters. This prospective study included 52 women with endometrial cancer (EC) who underwent MR imaging as initial staging in our hospital, allocated into low-grade (G1 and G2) and high-grade (G3) tumors according to the pathology reports. Regions of interest (ROIs) were drawn on the diffusion weighted images and apparent diffusion coefficient (ADC), true diffusivity (D), and perfusion fraction (f) using diffusion models were computed. Mean, median, skewness, kurtosis, and interquartile range (IQR) were calculated from the whole-tumor histogram. The IQR of the diffusion coefficient (D) was significantly lower in the low-grade tumors from that of the high-grade group with an adjusted p-value of less than 5% (0.048). The ROC curve analysis results of the statistically significant IQR of the D yielded an accuracy, sensitivity, and specificity of 74.5%, 70.1%, and 76.5% respectively, for discriminating low from high-grade tumors, with an optimal cutoff of 0.206 (×10−3 mm2/s) and an AUC of 75.4% (95% CI: 62.1 to 88.8). The IVIM modeling coupled with histogram analysis techniques is promising for preoperative differentiation between low- and high-grade EC tumors.

Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast.

Solid papillary carcinoma (SPC) is a rare but distinct clinicopathological feature of breast cancer characterised by frequent neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a useful neuroendocrine marker for various neuroendocrine tumours. α-thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) are useful prognostic markers for patients with pancreatic neuroendocrine tumours. However, to the best of our knowledge, few studies have addressed INSM1 expression in SPCs. Although ATRX, DAXX and δ-like canonical notch ligand 3 (DLL3) are frequently expressed in neuroendocrine lung carcinomas, there are no reports on their expression in SPCs. Therefore, the present study aimed to analyse the expression profiles of INSM1, ATRX, DAXX and DLL3 in the largest series of patients with SPC that has been, to the best of our knowledge, studied until now. Immunohistochemical analyses were performed to determine chromogranin A, synaptophysin, INSM1, ATRX, DAXX and DLL3 expression in 39 specimens surgically resected from patients with SPC (18 SPC in situ and 21 SPC invasive). The associations between the expression of these markers and the clinicopathological factors were investigated. Chromogranin A, synaptophysin and INSM1 were expressed in 64.1, 100 and 92.3% of the patients, respectively. Both ATRX and DAXX expression was observed in 28.2% of the patients. No patient expressed DLL3. Lack of INSM1 or chromogranin A expression was significantly associated with advanced pathological stages in patients with SPC (P=0.033) and in patients with invasive SPC (P=0.012), showing a tendency for a high Ki-67 labelling index (LI) and advanced histological grade in patients with invasive SPC. Loss of ATRX or DAXX expression was significantly associated with lymphatic invasion, but not with histological grade, Ki-67 LI or presence of invasive tumours. Thus, INSM1 was demonstrated to be a useful diagnostic marker for SPCs. Overall, detecting the lack of INSM1 or chromogranin A expression may be useful for analysing the characteristics of tumour cells in SPCs.

Elaboration of Multiparametric MRI-Based Radiomics Signature for the Preoperative Quantitative Identification of the Histological Grade in Patients With Non-Small-Cell Lung Cancer.

The histological grading plays an essential role in the treatment decision of lung cancer. Detected tumors are usually biopsied to confirm histologic grade. How to use MRI extracted radiomics features for accurately grading lung cancer is still challenging. To examine the diagnostic utility of multiparametric MRI radiomics and clinical factors for grading non-small-cell lung cancer (NSCLC). Retrospective. A total of 148 patients (25.7% female) with postoperative pathologically confirmed NSCLC and divided into the training cohort (N=110) and the validation cohort (N=38). A 1.5 T; single-shot turbo spin-echo (TSE), T2-weighted imaging (T2WI), and integrated shimming-echo planar imaging (ISHIM-EPI) diffusion-weighted imaging (DWI). A total of 2775 radiomics features were extracted from carcinomatous regions of interest on T2WI, DWI, and the apparent diffusion coefficient (ADC) maps. The five optimal features were selected by using the Student' s t-test, the least absolute shrinkage and selection operator (LASSO) and stepwise regression. The Radscore combined with clinical factors, which selected by univariate and multivariate analyses, to develop a radiomics-clinical nomogram. Its performance was evaluated in the training cohort and the validation cohort. The potential clinical usefulness was analyzed by the receiver operating characteristic curve (ROC), area under the curve (AUC), and the Hosmer-Lemeshow test. Student's t-test, univariate analyses, multivariate analyses, LASSO, ROC, AUC, and the Hosmer-Lemeshow test. P < 0.05 was considered statistically significant. Favorable discrimination performance was obtained for five optimal features (out of the 2775 features), using the training cohorts (AUC 0.761) and validation cohorts (AUC 0.753). In addition, the radiomics-clinical nomogram significantly improved the ability to identify histological grades in the training cohort (AUC 0.814) and the validation cohort (AUC 0.767). The radiomics-clinical nomogram based on multiparametric MRI might have the potential to distinguish the histological grade of NSCLC. 3 TECHNICAL EFFICACY: Stage 2.

Different Prognostic Role of EGFR Mutation According to the IASLC Histologic Grade in Patients with Resected Early-Stage Lung Adenocarcinoma

Different Prognostic Role of EGFR Mutation According to the IASLC Histologic Grade in Patients with Resected Early-Stage Lung Adenocarcinoma

Machine learning with multiparametric breast MRI for prediction of Ki-67 and histologic grade in early-stage luminal breast cancer.

To investigate whether machine learning-based prediction models using 3-T multiparametric MRI (mpMRI) can predict Ki-67 and histologic grade in stage I-II luminal cancer. Between 2013 and 2019, consecutive women with luminal cancers who underwent preoperative MRI with diffusion-weighted imaging (DWI) and surgery were included. For prediction models, morphology, kinetic features using computer-aided diagnosis (CAD), and apparent diffusion coefficient (ADC) at DWI were evaluated by two radiologists. Logistic regression analysis was used to identify mpMRI features for predicting Ki-67 and grade. Diagnostic performance was assessed using eight machine learning algorithms incorporating mpMRI features and compared using the DeLong method. Of 300 women, 203 (67.7%) had low Ki-67 and 97 (32.3%) had high Ki-67; 242 (80.7%) had low grade and 58 (19.3%) had high grade. In multivariate analysis, independent predictors for higher Ki-67 were washout component > 13.5% (odds ratio [OR] = 4.16; p < 0.001) and intratumoral high SI on T2-weighted image (OR = 1.89; p = 0.022). Those for higher grade were washout component > 15.5% (OR = 7.22; p < 0.001), rim enhancement (OR = 2.59; p = 0.022), and ADC value < 0.945 × 10-3 mm2/s (OR = 2.47; p = 0.015). Among eight models using these predictors, six models showed the equivalent performance for Ki-67 (area under the receiver operating characteristic curve [AUC]: 0.70) and Naive Bayes classifier showed the highest performance for grade (AUC: 0.79). A prediction model incorporating mpMRI features shows good diagnostic performance for predicting Ki-67 and histologic grade in patients with luminal breast cancers. • Among multiparametric MRI features, kinetic feature of washout component >13.5% and intratumoral high signal intensity on T2-weighted image were associated with higher Ki-67. • Washout component >15.5%, rim enhancement, and mean apparent diffusion coefficient value < 0.945 × 10-3 mm2/s were associated with higher histologic grade. • Machine learning-based prediction models incorporating multiparametric MRI features showed good diagnostic performance for Ki-67 and histologic grade in luminal breast cancers.

2-[18F]FDG PET/CT as a Predictor of Microvascular Invasion and High Histological Grade in Patients with Hepatocellular Carcinoma.

Simple SummaryIn recent years, functional imaging techniques have been increasingly studied to preoperatively identify the aggressive features in hepatocellular carcinoma (HCC). PET/CT with 2-deoxy-2-[18F]fluoro-d-glucose (FDG) is not routinely used for the diagnosis and staging of an HCC due to its low uptake of this radiopharmaceutical especially in well-differentiated lesions. However, FDG uptake in an HCC seems to relate to biological aggressiveness, being able to predict certain factors such as microvascular invasion. The present work aimed to assess the prognostic value of performing a baseline PET/CT with FDG in patients with an HCC who were subsequently treated with a tumor resection, trying to identify which metabolic parameters may predict the presence of histological factors of a poor prognosis. In our series, an increased SULpeak of the ratio tumor/liver 60 min after an FDG injection (TLRpeak60) seems a promising parameter to predict histological factors of a poor prognosis that could aid decision-making in this group of patients.Hepatocellular carcinoma (HCC) generally presents a low avidity for 2-deoxy-2-[18F]fluoro-d-glucose (FDG) in PET/CT although an increased FDG uptake seems to relate to more aggressive biological factors. To define the prognostic value of PET/CT with FDG in patients with an HCC scheduled for a tumor resection, forty-one patients were prospectively studied. The histological factors of a poor prognosis were determined and FDG uptake in the HCC lesions was analyzed semi-quantitatively (lean body mass-corrected standardized uptake value (SUL) and tumor-to-liver ratio (TLR) at different time points). The PET metabolic parameters were related to the histological characteristics of the resected tumors and to the evolution of patients. Microvascular invasion (MVI) and a poor grade of differentiation were significantly related to a worse prognosis. The SULpeak of the lesion 60 min post-FDG injection was the best parameter to predict MVI while the SULpeak of the TLR at 60 min was better for a poor differentiation. Moreover, the latter parameter was also the best preoperative variable available to predict any of these two histological factors. Patients with an increased TLRpeak60 presented a significantly higher incidence of poor prognostic factors than the rest (75% vs. 28.6%, p = 0.005) and a significantly higher incidence of recurrence at 12 months (38% vs. 0%, p = 0.014). Therefore, a semi-quantitative analysis of certain metabolic parameters on PET/CT can help identify, preoperatively, patients with histological factors of a poor prognosis, allowing an adjustment of the therapeutic strategy for those patients with a higher risk of an early recurrence.