Grade Of Carcinoma Research Articles

Development and validation of intravoxel incoherent motion diffusion weighted imaging-based model for preoperative distinguishing nuclear grade and survival of clear cell renal cell carcinoma complicated with venous tumor thrombus

ObjectiveTo assess the utility of multiparametric MRI and clinical indicators in distinguishing nuclear grade and survival of clear cell renal cell carcinoma (ccRCC) complicated with venous tumor thrombus (VTT).Materials and methodsThis study included 105 and 27 patients in the training and test sets, respectively. Preoperative MRI, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), was performed. Renal lesions were evaluated for IVIM-DWI metrics and conventional MRI features. All the patients had postoperative histologically proven ccRCC and VTT. An expert uropathologist reviewed all specimens to confirm the nuclear grade of the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) of the tumor. Univariate and multivariable logistic regression analyses were used to select the preoperative imaging features and clinical indicators. The predictive ability of the logistic regression model was assessed using receiver operating characteristic (ROC) analysis. Survival curves were plotted using the Kaplan–Meier method.ResultsHigh WHO/ISUP nuclear grade was confirmed in 69 of 105 patients (65.7%) in the training set and 19 of 27 patients (70.4%) in the test set, respectively (P = 0.647). Dp_ROI_Low, tumor size, serum albumin, platelet count, and lymphocyte count were independently related to high WHO/ISUP nuclear grade in the training set. The model identified high WHO/ISUP nuclear grade well, with an AUC of 0.817 (95% confidence interval [CI]: 0.735–0.899), a sensitivity of 70.0%, and a specificity of 77.8% in the training set. In the independent test set, the model demonstrated an AUC of 0.766 (95% CI, 0.567–0.966), a sensitivity of 79.0%, and a specificity of 75.0%. Kaplan–Meier analysis showed that the predicted high WHO/ISUP nuclear grade group had poorer progression-free survival than the low WHO/ISUP nuclear grade group in both the training and test sets (P = 0.001 and P = 0.021).ConclusionsIVIM-DWI-derived parameters and clinical indicators can be used to differentiate nuclear grades and predict progression-free survival of ccRCC and VTT.

Development and validation of a radiomics-based nomogram for predicting pathological grade of upper urinary tract urothelial carcinoma

BackgroundUpper urinary tract urothelial carcinoma (UTUC) is a rare and highly aggressive malignancy characterized by poor prognosis, making the accurate identification of high-grade (HG) UTUC essential for subsequent treatment strategies. This study aims to develop and validate a nomogram model using computed tomography urography (CTU) images to predict HG UTUC.MethodsA retrospective cohort study was conducted to include patients with UTUC who underwent radical nephroureterectomy and received a CTU examination prior to surgery. In the CTU images, tumor lesions located in the renal calyces, renal pelvis and ureter were segmented, and radiomics features from the unenhanced, medullary, and excretory phases were extracted. The maximum relevance minimum redundancy algorithm, least absolute shrinkage and selection operator, and various machine learning (ML) algorithms—including random forest, support vector machine, and eXtreme gradient boosting—were employed to select radiomics features and calculate radiomics scores. Logistic regression (LR) analysis was performed to identify the independent influencing factors of clinical baseline characteristics. Multiple datasets of radiomics features were constructed by integrating single-phase radiomics features with the most significant independent factor. Both LR and ML algorithms were utilized to develop predictive models. The area under the receiver operating characteristic curve (AUC values), accuracy, sensitivity, and specificity were assessed for model performance evaluation. Decision curve analysis was conducted to evaluate the clinical net benefits.ResultsA total of 167 patients were enrolled in this study. Among them, 56 were diagnosed with low-grade UTUC (including papillary urothelial neoplasms with low malignant potential and low-grade urothelial carcinoma) as confirmed by postoperative pathological examination results, and 111 were of HG. These patients were randomly allocated to the training set and the validation set at a ratio of 7:3. The training set comprised 116 patients with a mean age of 63.5 ± 9.38 years and 38 males. The validation set comprised 51 patients with a mean age of 65.6 ± 11.1 years and 18 males. Hydronephrosis was identified as the most significant independent factor in the clinical baseline features. Models that include mixed-phase development achieve better performance compared to models that rely simply on single-phase development. The nomogram model had excellent predictive ability for HG UTUC, with AUC values of 0.844 and an accuracy of 0.793 in the validation sets. The nomogram model can enhance accuracy by 14.1% (79.3% vs. 65.2%) and sensitivity by 32.8% (93.2% vs. 60.4%) compared to urinary cytology.ConclusionsThis study developed a nomogram model, which significantly improved the diagnostic ability for HG UTUC compared to urinary cytology. Furthermore, the results of the decision curve analysis showed that the model had a net benefit and could provide a non-invasive and potentially diagnostic reference tool for HG UTUC.

Multi-modal clear cell renal cell carcinoma grading with the segment anything model

Multi-modal clear cell renal cell carcinoma grading with the segment anything model

Validation of salivary proteomic biomarkers for early detection of oral cancer in the Egyptian population.

The present study evaluated the sensitivity and specificity of important proteomic salivary biomarkers; IL-6, IL-8, and sCD44 in the early detection of oral cancer, and any possible associations with risk factors of oral cancer in an Egyptian population. The present investigation was conducted on 100 individuals; 25 healthy controls, 25 patients having oral potentially malignant disorders (OPMDs) with dysplasia; 25 patients having OPMDs without dysplasia, and 25 oral cancer patients. Demographic data modified gingival index, oral hygiene level, and salivary levels of the biomarkers were assessed. Salivary levels of IL-6, IL-8, and sCD44 progressively increased with increased disease severity. Salivary IL-8 and IL-6 levels possess a discriminating potential from normal tissue through different degrees of dysplasia to oral cancer, sCD44 levels had a discriminating power between normal and dysplastic tissues with high sensitivity and specificity. A positive correlation was found between the three biomarkers and the grade of oral squamous cell carcinoma (OSCC) and with different risk factors. This is the first study that evaluated multiple salivary proteomic biomarkers in the Egyptian population, and the results validate the ability of IL-6, IL-8, and sCD44 to be used as sensitive diagnostic and prognostic biomarkers for screening and early detection of oral cancer.

Investigation of HOTAIR rs12826786, rs920778 and rs4759314 variants with breast cancer susceptibility and clinicopathological characteristics in a Mexican population

BackgroundBreast cancer (BC) is a multifactorial disease of unknown etiology whose major risk factors are genetic alterations of cell proliferation and migration pathways. HOX transcript antisense RNA gene (HOTAIR) is a long non-coding RNA (lncRNA) related to cell proliferation, progression, invasion, metastasis, and poor survival of multiple cancers, including BC. Controversial results have emerged on the association between breast cancer risk in multiple ethnicities. This study explores the association of rs12826786, rs920778, and rs4759314 variants in the HOTAIR gene in BC patients. MethodsDNA of peripheral blood samples was obtained from 588 women (289 patients and 299 control females). Genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The association was calculated using the odds ratio (OR) test. P-values were adjusted by the Bonferroni test (0.016). ResultsThe rs12826786 (C>T), rs920778 (T>C), and rs4759314 (A>G) variants were associated with BC and with TNM stage, histologic type, and histologic molecular subtype (P=0.001). Likewise, the haplotype C-T-G in the HOTAIR gene (rs12826786-rs920778-rs4759314) was significantly related to BC (OR= 5.44, 95%, CI= 2.22-13.32, P= 0.001). ConclusionThe results suggest that rs12826786, rs920778, and rs4759314 variants in HOTAIR significantly influence breast cancer risk. Micro-abstractHOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA strongly correlated with the tumor grade and prognosis of various carcinomas, including breast cancer (BC). In this study, we analyzed the association of the rs12826786, rs920778, and rs4759314 variants in the HOTAIR gene and observed an increased susceptibility to BC and clinicopathological characteristics in a Mexican population.

Non-radiomics imaging (US-CEUS) features and clinical text features: correlation with microvascular invasion and tumor grading in hepatocellular carcinoma.

To predict microvascular invasion (MVI) status and tumor grading of hepatocellular carcinoma (HCC) by evaluating preoperative non-radiomics ultrasound and contrast-enhanced ultrasound (US-CEUS) features and determine the influences of MVI/tumor grading on the category of CEUS LI-RADS for HCC. A total of 506 HCC patients who underwent preoperative US-CEUS examinations from 8 hospitals between July 2020 and June 2023 were enrolled. According to the MVI status, all the patients were classified, and HCC differentiation was assessed by using Edmondson-Steiner (ES) grading: MVI-negative (M0) and low-grade ES (GI/II) (MN-L, n = 297) and MVI-positive (M1/M2) and/or high-grade ES (GIII/IV) (MP-H, n = 209). Stratified analysis was performed based on fibrosis stage and tumor size. The results proved that MN-L HCC was more frequently classified into the LR-5 category (p = 0.034), while MP-H HCC was more frequently classified into the LR-TIV (p = 0.010). The heterogeneously arterial phase hyperenhancement (APHE) is significantly correlated with MVI(+)/high grade-ES (p = 0.003). Compared with MN-L HCC, the onset of washout was earlier, washout rate was higher, and tumor-invasion border was larger (all p < 0.01) in MP-H HCC. In addition, fibrosis stage and tumor size significantly influenced the onset of washout and washout rate of HCC (all p < 0.01). The tumor-invasion border was only positively correlated with tumor size (p < 0.001) rather than fibrosis stage (p > 0.05). MVI status and tumor grading influence the classification of LR-5 and LR-TIV. Heterogeneous APHE, higher washout rate, earlier onset of washout (≤65s), larger tumor-invasion border (≥3mm) and higher alpha fetoprotein level indicate the presence of MVI and/or high-grade ES.

The value of radiomics based on 2-[18 F]FDG PET/CT in predicting WHO/ISUP grade of clear cell renal cell carcinoma

BackgroundThe aim is to develop and validate radiomics based on 2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) parameters for predicting the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of clear cell renal cell carcinoma (ccRCC).MethodsA total of 209 patients with 214 lesions, who underwent 2-[18F]FDG PET/CT scans between December 2016 to December 2023, were included in our study. All ccRCC lesions were categorized into low grade (WHO/ISUP grade I-II) and high grade (WHO/ISUP grade III-IV). The lesions were allocated into a training group and a testing group in a ratio of 7:3. The radiomics features were extracted by a serious of maximum standardized uptake value (SUVmax) thresholds (0,2.5%,25%,40%) with the utilization of the minimum redundancy and maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithm. The clinical, radiomics and combined models were constructed. The receiver operating characteristic (ROC) curve, decision curve and calibration curves were plotted to assess the predicting performance.ResultsThe area under curve (AUC) of PET-0, PET-2.5%, PET-25%, PET-40% model in the training group were 0.881(95% CI: 0.822–0.940),0.883(95% CI: 0.825–0.942),0.889(95% CI: 0.831–0.946),0.887(95% CI: 0.826–0.948); and 0.878(95% CI: 0.777–0.978),0.876(95% CI: 0.776–0.977),0.871(95% CI: 0.769–0.972),0.882(95% CI: 0.786–0.979) in the testing group. Due to perfect prediction and verification performance, the volume of interest (VOI) from PET images with SUVmax threshold of 40% were selected to construct the radiomics model and combined model. The AUC of the clinical model and radiomics model was 0.859 (sensitivity = 0.846, specificity = 0.747) and 0.909 (sensitivity = 0.808, specificity = 0.751) in the training group, respectively; 0.882 (sensitivity = 0.857, specificity = 0.857) and 0.901 (sensitivity = 0.905, specificity = 0.833) in the testing group, respectively. In combined models, the AUC was 0.916, the sensitivity was 0.923 and the specificity was 0.808 in the training group; the AUC was 0.916, the sensitivity was 0.881 and the specificity was 0.792 in the training group.ConclusionRadiomics based on 2-[18F]FDG PET/CT can be helpful to predict WHO/ISUP grade of ccRCC.

Quantitative proteogenomic characterization in MUC1 and MUC4 in oral squamous cell carcinoma, oral potentially malignant disorders, and normal oral mucosa in carcinogenesis.

Mucins are glycoproteins with a significant molecular weight that have a diverse range of biological functions. MUC1 & MUC4 are transmembrane mucin family members that are expressed in airway epithelial cells and body fluids. It is expressed excessively in numerous carcinomas in addition to their alteredexpression. A thorough review of the literature reveals very limited research about MUC1 & 4 expressionsin oral malignancies and oralpremalignant disorders. The aim of the research is to assess the pattern and quantity of gene expression in MUC1 & MUC4 individually in various grades of oral squamous cell carcinoma (OSCC), oral premalignant disorders (OPMDs)- oral epithelial dysplasia (OED), oral submucous fibrosis (OSF), oral lichen planus (OLP), and compared with normal oral mucosa (NOM). Immunohistochemistry and qRTPCR evaluation of MUC1 & 4 on sixty-three cases of OSCC, OPMD, and NOM was accomplished. The one-way ANOVA test and Chi-square test were done for statistical analysis. The overall immunoexpression of MUC1 & 4 increased significantly from NOM to OPMDs to OSCC. In the subgrades of OSCC and OPMDs, the staining intensity varied. For MUC4, the intensity was strongest in well-differentiated grades and MUC1, exhibiting a higher expression in poorly differentiated grades of OSCC and OPMDs. The study's results indicate that MUC1 & 4 individually are crucial formonitoringOSCC and OPMD pathogenesis as the former gives an idea of highly undifferentiated grades while the latter indicated more differentiated tumors and perhaps a better prognosis. Therefore, the two can be useful tumor markers for determining the severity and eliminating it in its early phases.

Phosphorylated protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression in breast cancer is correlated with malignant proliferation and histological grading.

This study aims to detect the expression of phosphorylated PERK in breast cancer using immunohistochemistry and explore its significance. We examined 134 cases of formalin-fixed and paraffin-embedded breast cancer tissues. It was found that the expression of phosphorylated PERK in ductal carcinoma was higher than that in lobular carcinoma, and the difference between them was statistically significant, suggesting that phosphorylated PERK played different roles in the occurrence and development of different types of breast cancer. Compared with Ki-67-negative breast cancer tissues, phosphorylated PERK has higher expression in Ki-67-positive tissues and is positively correlated with Ki67 expression, indicating that phosphorylated PERK plays an important role in breast cancer's malignant proliferation and progression. We also found a positive correlation between phosphorylated PERK expression and the histological grading of invasive ductal carcinoma, indicating that phosphorylated PERK plays an important role in the differentiation of invasive ductal carcinoma. Our study revealed the differential expression of phosphorylated PERK in subtypes of breast cancer. It contributed to the malignant proliferation of breast cancer and tissue differentiation of invasive ductal carcinoma of the breast.

Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan.

In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification. We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and univariate and multivariate analyses. The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively). Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.

Expression of p53 Protein in Different Grades of Gastric Carcinoma

Background: Mutation in the TP53 suppressor gene and accumulation of p53 protein are the common genetic events in gastric carcinomas. This mutation has been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and suggested to be implicated in the prognosis of gastric carcinoma. Objectives: To assess the immunohistochemical expression of p53 protein in gastric carcinoma and to study the association of p53 protein expression with different histopathological grade of gastric carcinoma. Methods: In this cross-sectional observational study, 60 paraffin blocks of gastric adenocarcinoma were re-evaluated and histopathological grading were assessed. The p53 expression in the tumour cell nucleus of the submitted blocks were assessed by standard immunoperoxidase method. Appropriate positive control was run for each batch of slides. Results: Out of 60 cases, most of them 35 cases were poorly differentiated carcinoma, of which 28(80%) showed high expression and 7(20%) showed low expression of p53 protein. Twenty cases were moderately differentiated carcinoma, of which 12(60%) showed high expression and 8(40%) low expression. Only 5 were well differentiated carcinoma and all of which showed low expression of p53 protein. So, it was seen that with advancing grade of tumor, frequency of high expression of p53 protein was high and yielded statistically significant result (p value = 0.001). Conclusion: There was a significant association between immunohistochemical expression of p53 protein and histopathological grading of gastric adenocarcinoma. These results indicate that immunohistochemical expression of p53 protein is an important prognostic factor of gastric adenocarcinoma, allowing the selection of a group of patients with an extensive therapeutic indication. Mediscope 2024;11(2): 48-51

Grading of clear cell renal cell carcinoma by using monoexponential, biexponential, and stretched exponential diffusion-weighted MR imaging.

To evaluate the diagnostic accuracy of monoexponential, biexponential and stretched-exponential diffusion-weighted imaging (DWI) models in the grading of clear cell renal cell carcinoma (ccRCC). Fifty-one patients with pathologically proven ccRCC underwent DWI with fifteen b factors (0, 10, 30, 50, 70, 100, 150, 200, 300, 400, 600, 800, 1000, 1500, 2000 sec/mm²) on a 3.0T MR scanner. The isotropic apparent diffusion coefficient (ADC), true diffusion coefficient (ADCslow), pseudodiffusion coefficient (ADCfast), and fraction of perfusion (f) were derived from DWI using a biexponential model. The water diffusion heterogeneity index (α) and distributed diffusion coefficient (DDC) were derived from DWI using a stretched-exponential model. All values were calculated for the solid area of tumors and compared between high-grade and low-grade ccRCC. The Mann-Whitney U test and receiver operating characteristic (ROC) analysis were used for statistical analysis. The DeLong test was performed to compare the ROC curves. The mean ADC, DDC, ADCslow and α values were significantly lower in high-grade ccRCC than in low-grade ccRCC (P< 0.01). However, the ADCfast and f were not significantly different between the two groups (P > 0.05). According to the ROC analyses, the AUC for α was 0.941, which was significantly greater than those of the other parameters, with a sensitivity of 100% and a specificity of 84.2%. The DeLong test showed that there were significant differences in the ROCs among ADCfast/ADC, ADCfast/α, f/ADCslow, ADCfast/ADCslow, f/α, DDC/α, and f/ADC. Diffusion-related parameters (ADC, DDC, ADCslow and α) could be used to distinguish between low- and high-grade ccRCC. The α derived from the stretched-exponential model may be the most promising parameter for grading ccRCC.

Relevance of the Immunohistochemical Expression of p53 and E-cadherin in the Grading of Urothelial Carcinoma: A Single-Center Cross-Sectional Observational Study.

Background Urothelial carcinoma (UC) is a prevalent cancer worldwide, primarily affecting the urinary bladder. It is more common in men than women and is often linked to factors like tobacco smoking, occupational exposure, and chronic infections. UC can be classified into different subtypes based on its growth pattern (papillary or non-papillary) and the extent of invasion into the bladder wall. The management of UC depends on its grade and stage, with treatment options ranging from transurethral resection of bladder tumor (TURBT) for non-invasive tumors to cystectomy for muscle-invasive disease. This study aimed to investigate the expression of p53 and E-cadherin in low-grade and high-grade UC and their correlation with histomorphological parameters. Materials and methods A cross-sectional observational study was conducted on 50 histopathologically confirmed UC cases. Immunohistochemical (IHC) staining for p53 and E-cadherin was performed, and the results were correlated with clinicopathological features. Statistical analysis was performed to find the correlation between p53 and E-cadherin immunoexpression and the grade of UC. Results The cohort's mean age was 58.18±12.99 years, with a male predominance (76%). Most cases (52%) were from rural areas and unskilled workers (52%). Hematuria was present in all cases (100%), while urgency and frequency were reported in 32% each. High-grade UC was more common (76%), with 48% being invasive. Muscle invasion was absent in 56%. p53 overexpression was seen in all cases, with 38% moderate and 36% strong staining. Twenty-two out of 24 cases (91.7%) of invasive UC showed low E-cadherin expression, while all 26 cases (100%) of low-grade papillary UC and high-grade papillary UC displayed high E-cadherin expression. This suggests that reduced E-cadherin expression is strongly associated with invasive UC, potentially as a tumor aggressiveness and progression marker. Conclusion Considering that elevated p53 protein expression is linked to aggressive tumor behavior, a more intensive treatment strategy is recommended for patients with non-muscle-invasive bladder cancer (NMIBC) who show high p53 protein scores. On the other hand, the downregulation or absence of E-cadherin expression has been recognized as a strong indicator of advanced grade and higher clinical stages.

Chromosome 8q24 amplification associated with human hepatocellular carcinoma predicts MYC/ZEB1/MIZ1 transcriptional regulation.

Genomic instability is associated with late stage carcinomas and the epithelial mesenchymal transition (EMT). Of note is chromosome 8q24 amplification that has been documented in many epithelial-derived carcinomas. On this amplified region is the potent oncogene, c-myc. Not only does MYC overexpression activate targets that promote cell proliferation, it also activates transcription factors that drive EMT, including ZEB1. Further reinforcing EMT, overexpressed MYC also represses tumor suppressors involved in promoting the epithelial phenotype, including MIZ1. We predict that as carcinomas progress, chromosome 8q24 is amplified leading to high MYC levels that leads to ZEB1 expression and MIZ1 repression driving cells through EMT. To interrogate this clinically, limited cohorts of human epithelial-derived carcinomas were examined for MYC/ZEB1/MIZ1 expression patterns across increasing carcinoma grades. Interestingly, the predicted temporal patterns were only observed in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinomas. Yet MIZ1 proved to be an excellent marker to assess carcinoma progression across types. We expanded the HCC cohort and determined that c-myc amplification was restricted to grade III/IV HCC that also exhibited increased MYC and ZEB1 nuclear expression whereas cytosolic MIZ1 expression was lost and only nuclear expression retained. These same resections were obtained from only individuals who had histories of alcohol consumption that were also diagnosed with cirrhosis, metastasis and had viral hepatitis suggesting etiology-specific mechanisms of cancer progression. Finally, analysis performed in Hep3B cells determined that alterations in MYC expression promoted the predicted changes in ZEB1 and MIZ1 expression and/or distributions and in markers for EMT further suggesting a relationship among these three transcription factors in HCC and their correlation to driving EMT.

Epidemio-Clinical, Anatomopathological, Computed Tomography Aspects from Breast Cancer to Imaging and Medical Oncology Departments at Chu – Mother-Child “Luxembourg”

Introduction: Cancer results from an anarchic proliferation of abnormal cells of the mammary gland and is the most common cancer in women in developed countries with 50,000 new cases in 2008. Objectives: The aim of our work was to describe the sociodemographic characteristics of patients, to determine the different sites and the frequency of metastases; and to describe the CT and histological aspects in the diagnosis of extension, therapy and assessment. Methods: Our study was retrospective descriptive over a period of 12 months from January 2020 to December 2020 in the radiology and medical oncology department of CHUME Luxembourg. It concerned all patients with histologically confirmed cancer who had undergone a scan before, during treatment or during therapeutic monitoring. The examinations were carried out with a HITACHI SUPRIA 16 BARRETTES CT scanner installed in 2015. Results: During the period of our study, the frequency of breast cancer was 10.7% (130 cases) out of 1204 scans carried out with a female predominance of 98%, an average age of 52 years and extremes of 12 to 90 years. The main metastases were: pulmonary (59%), followed by lymph node metastases (66%), bone (51%), liver (29%) and brain (2%). The association of pulmonary, lymph node, liver and bone metastasis represented 27% of the most frequent associations. As for the histological aspect, non-specific invasive carcinoma grade II SBR and TNM was the most frequent.

8126 PTH-Independent, Calcitriol-Mediated Hypercalcemia In Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

8126 PTH-independent, Calcitriol-mediated Hypercalcemia in Renal Cell Carcinoma

Abstract Disclosure: G.K. Rai: None. A. De Rosairo: None. K. Madani: None. D. Sacoto: None. A.A. Franco-Akel, MD: None. R. Belokovskaya: None. Hypercalcemia of malignancy is a known complication of advanced cancer. It occurs through various mechanisms, one of which is via 1,25-dihydroxyvitamin D (calcitriol). Calcitriol-mediated hypercalcemia accounts for approximately 1% of cases of hypercalcemia in the setting of malignancy and is usually seen in lymphomatous solid tumors. We present a gentleman with clear cell renal cell carcinoma associated with hypercalcemia with normal levels of intact parathyroid hormone (PTH), PTH-related protein (PTHrP), and 25-hydroxyvitamin D but elevated calcitriol levels. A 48 year-old-male with no significant past medical history with complaints of fatigue, hematuria, and weight loss of 38 pounds in 3 months was following urology for an elective right-sided nephrectomy. MRI of the abdomen and pelvis found a 16.1 cm renal mass with necrotic areas, causing mass effects on the liver, pancreas, and IVC. Preoperative laboratory showed hypercalcemia of 13.7 mg/dL (corrected 13.9 mg/dL) with microcytic anemia (hemoglobin 8.8 g/dL, MCV 72 fl). Workup showed low iPTH (3 pg/dL), 25-hydroxyvitamin D (16.9 ng/dL), and phosphorus level (1.7mg/dL) with elevated calcitriol (94.3 pg/dL) and a normal PTHrP. CT chest showed multiple pulmonary nodules on bilateral lobes, with the largest nodule ∼ 4.5 mm. Hypercalcemia was managed with IV fluids, calcitonin 300 units Q12 for two days, Denosumab IV infusion, prednisone 60 mg for three days, and oral ergocalciferol 50,000 units weekly. Calcium levels normalized, after which the patient underwent nephrectomy. Pathology revealed renal cell carcinoma grade G4 with mixed features of clear cell carcinoma with sarcomatoid and rhabdoid features. We report an incidental finding of hypercalcemia in a patient with renal mass. The elevated calcitriol levels can be attributed to ectopic calcitriol production through the renal mass. Post nephrectomy calcium levels remained within normal range for consecutive weeks. With this, we concur that hypercalcemia most likely originated from the renal mass that had ectopic production of calcitriol. Dysregulated calcitriol production is a well-known complication of lymphomas and granulomatous disease but is seldom reported with solid tumors. Usually, the etiology for hypercalcemia in patients with renal cell carcinoma is the overproduction of PTHrP, which was not the case with our patient. The ultimate resolution of hypercalcemia of malignancy was attained by treating the underlying malignancy. Presentation: 6/1/2024

Molecular profiling of oral epithelial dysplasia and oral squamous cell carcinoma using next generation sequencing

BackgroundNext generation sequencing (NGS) is a massive, high-throughput sequencing technology used to analyze various mutations and genetic changes in cancer. Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck region. OSCC usually arises from oral potentially malignant disorders, like oral leukoplakia, oral submucous fibrosis and erythroplakia, and shows mutation of tumor suppressor genes, and several other critical genes involved in apoptotic pathways, cell migration, and cell growth. AimTo analyze the molecular profiles of oral epithelial dysplasia and different grades of oral squamous cell carcinoma using NGS in the Indian subpopulation. Methodology21 patients (5 patients each of well differentiated, moderately differentiated, poorly differentiated squamous cell carcinoma, severe epithelial dysplasia, and 1 normal appearing mucosal tissue from apparently healthy individuals) were included in the study. Next generation sequencing was carried out using 50 hotspot gene panel. Protein-protein analysis was carried out using STRING Consortium 2023 and the methylation profile of the expressed genes was evaluated using the UALCAN portal. ResultsSevere epithelial dysplasia showed TP53 (c.743G>A, p.R248Q) pathogenic mutations (SNV) in suboptimal QC parameters. Well differentiated squamous cell carcinoma showed TP53 (c.328delC, p.Arg110fs*13), APC (c.4135G>T, p.Glu1379*), and FBXW7 (c.832C>T, p.Arg278*) mutations. CTNNB1 (c.134C>T, p.Ser45PheS45F), TP53 (c.637C>T, Arg213TerR213*), NRAS (c.183A>C, p.Gln61HisQ61H) and PDGFRA (c.1672C>T, p.Arg558Cys) mutations were seen in moderately differentiated squamous cell carcinoma. No pathogenic mutations were evident in poorly differentiated squamous cell carcinoma. STRING analysis showed that all the expressed proteins in each group were interrelated to each other. No significant difference was evident in the methylation profile of all the expressed genes when compared to the normal controls. ConclusionThe results obtained in this study explain the diverse genetic mutations in various grades of oral squamous cell carcinoma. Identification of these mutations would help in providing better treatment, designing a proper treatment plan for the patients with OSCC and support minimal intervention medicine.

Expression Of TGF-Β In Oral Papillary Squamous Cell Carcinoma and Different Histological Grades of Oral Squamous Cell Carcinoma: An Immunohistochemical Comparative Study

Expression Of TGF-Β In Oral Papillary Squamous Cell Carcinoma and Different Histological Grades of Oral Squamous Cell Carcinoma: An Immunohistochemical Comparative Study

Multi-sequence MRI-based radiomics model to preoperatively predict the WHO/ISUP grade of clear Cell Renal Cell Carcinoma: a two-center study

ObjectivesTo develop radiomics models based on multi-sequence MRI from two centers for the preoperative prediction of the WHO/ISUP grade of Clear Cell Renal Cell Carcinoma (ccRCC).MethodsThis retrospective study included 334 ccRCC patients from two centers. Significant clinical factors were identified through univariate and multivariate analyses. MRI sequences included Dynamic contrast-enhanced MRI, axial fat-suppressed T2-weighted imaging, diffusion-weighted imaging, and in-phase/out-of-phase images. Feature selection methods and logistic regression (LR) were used to construct clinical and radiomics models, and a combined model was developed using the Rad-score and significant clinical factors. Additionally, seven classifiers were used to construct the combined model and different folds LR was used to construct the combined model to evaluate its performance. Models were evaluated using receiver operating characteristic (ROC) curves, area under the curve (AUC), and decision curve analysis (DCA). The Delong test compared ROC performance, with p < 0.050 considered significant.ResultsMultivariate analysis identified intra-tumoral vessels as an independent predictor of high-grade ccRCC. In the external validation set, the radiomics model (AUC = 0.834) outperformed the clinical model (AUC = 0.762), with the combined model achieving the highest AUC (0.855) and significantly outperforming the clinical model (p = 0.003). DCA showed that the combined model had a higher net benefit within the 0.04–0.54 risk threshold range than clinical model. Additionally, the combined model constructed using logistic regression has a higher priority compared to other classifiers. Additionally, 10-fold cross-validation with LR for the combined model showed consistent AUC values (0.849–0.856) across different folds.ConclusionThe radiomics models based on multi-sequence MRI might be a noninvasive and effective tool, demonstrating good efficacy in preoperatively predicting the WHO/ISUP grade of ccRCC.