Nuclear Grade Research Articles

Impact of a 7-Gene Predictive Biosignature on Adjuvant Radiation Therapy Recommendations in Patients Undergoing Breast-Conserving Surgery for Ductal Carcinoma in Situ.

Breast conservation therapy for patients with DCIS includes breast conserving surgery (BCS) with post-operative radiotherapy (RT). Because RT does not impact overall survival, identifying women who do not benefit from RT would allow de-escalation of therapy. We evaluated the impact of a novel 7-gene DCIS biosignature on adjuvant radiation recommendations for patients undergoing BCS for DCIS. 7-gene biosignature was evaluated in women diagnosed with DCIS between 2019-2022. 7-gene biosignature is reported as a "decision score" (DS) and categorical risk groups. RT recommendation before and after 7-gene biosignature was identified through retrospective chart review after IRB approval. The impact of DCISionRT on RT recommendations was assessed using McNemar's test. The 7-gene biosignature decision score (DS) was compared between treatment types by t-test. 101 patients underwent BCS for DCIS. Of those, 24 (24%) met RTOG 9804 criteria and 45 (45%) had nuclear grade 3 DCIS. Prior to 7-gene biosignature testing, all 101 patients were recommended RT; after testing, 35 patients omitted RT, corresponding to a 35% decision change (p<0.0001). Patients who ultimately omitted radiation had a significantly lower decision score (DS median 0.9) versus those who received RT (DS median 3.7) (p<0.0001). There were 22 of 39 patients (56%) with DS<2 and 11 of 40 patients (28%) with DS 2-4 who were not treated with RT. More patients with DS>4 (20/22, 91%) were treated with RT than DS<2, p<0.001, and patients with DS>4 were treated with an increased RT dose, p=.028. 7-gene biosignature test resulted in a 35% reduction in patients treated with adjuvant RT. Patients with higher decision scores were more likely to receive RT and to receive a greater RT dose.

Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma

Background/Objectives: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clinicopathological parameters and prognosis of patients with PeM. Methods: In a cohort of 13 MpeM patients, we evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, Ki67, BAP1, MTAP and p16 expression by immunohistochemistry, p16/CDKN2A status by FISH and TERT mRNA expression by RNAscope. Results: Our results showed several statistical correlations between TERT mRNA-score and other investigated features: (i) a poor positive correlation with BAP1 score (r = 0.06340; p ≤ 0.0001); (ii) a moderate positive correlation with p16 FISH del homo (r = 0.6340; p ≤ 0.0001); (iii) a fair negative correlation with p16 FISH del hetero (r = −0.3965; p ≤ 0.0001); a negative poor correlation with MTAP (r = −0.2443; p ≤ 0.0001); and (iv) a negative fair correlation with inflammatory infiltrate (r = −0.5407; p = 0.0233). Moreover, patients survive for a significantly longer time if they have a low mitotic index adjusted (2–4 mitotic figures per 2 mm2) (p ≤ 0.0001), are male (p = 0.0152), lose BAP1 (p = 0.0152), are p16 positive and present no deletion or heterozygous for p16 (p ≤ 0.01). Conclusions: TERT is highly expressed in PeM, but it is not one of the crucial factors in evaluating the prognosis of patients. Nevertheless, the results validate the prognostic significance of the mitotic index, BAP1 loss and p16/CDKN2A status.

Correlation of Histologic Features with Gene Alterations in Pleural Mesothelioma.

Histologic features, including architectural patterns, cytologic features, and 2021 World Health Organization nuclear grade have been shown to have prognostic significance in epithelioid diffuse pleural mesothelioma (DPM). Biphasic and sarcomatoid DPM, regardless of morphology, have worse outcomes. These prognostic findings are well-established but correlation of architectural patterns, cytologic features, and nuclear grade with genetic alterations has not been well studied. To investigate relationships between histologic findings and genomic alterations, 128 treatment-naïve DPM specimens (70% epithelioid, 23% biphasic and 6.3% sarcomatoid) with next generation sequencing data were retrospectively reviewed. Alterations in BAP1 were the most common genomic alteration (n=62, 48%), followed by CDKN2A (n=49, 38%) and NF2 (n=38, 30%). NF2 alterations were significantly more frequent in biphasic DPM (53% in biphasic versus 25% in sarcomatoid and 22% in epithelioid; p=0.005). In epithelioid DPM, TP53 alterations were associated with presence of prognostically unfavorable histology, including micropapillary or solid architecture, pleomorphic features and high nuclear grade. Tumors with low tumor infiltrating lymphocytes had a higher rate of BAP1 alterations compared to tumors with higher levels of tumor infiltrating lymphocytes (67% versus 30%; p=0.002). The findings of this study enhance our understanding of the relationships among prognostically significant histologic and molecular features of DPM and provide preliminary data to support increased integration of these findings in clinical diagnosis of pleural mesothelioma.

Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C‐Jun‐mediated IL‐8 Autocrine

AbstractTumor necrosis factor receptor‐associated factor 4 (TRAF4), an E3 ubiquitin ligase, is frequently overexpressed in tumors. Although its cytoplasmic role in tumor progression is well‐documented, the precise mechanisms underlying its nuclear localization and functional contributions in tumor cells remain elusive. This study demonstrated a positive correlation between the expression of nuclear TRAF4 and both tumor grades and stemness signatures in human cancer tissues. Notably, reduced nuclear TRAF4 led to decreased stemness properties and metastatic dormancy of tumor cells. Conversely, restoring nuclear TRAF4 in TRAF4‐knockout (TRAF4‐KO) cells augmented these cellular capabilities. Within the nucleus, the TRAF domain of TRAF4 interacted with c‐Jun, thereby stimulating its transcriptional activity. This interaction subsequently led to an enhancement of the promoter activity of interleukin‐8 (IL‐8), which is identified as a mediator of nuclear TRAF4‐induced tumor dormancy. Additionally, activation of AKT signaling by nerve growth factor facilitated TRAF4 phosphorylation at Ser242, enhancing its interaction with 14‐3‐3θ and promoting its nuclear translocation. Importantly, pharmacological modulation of TRAF4 nuclear translocation is found to suppress tumor tumorigenicity and metastasis in tumor models. This study highlights the critical role of nuclear TRAF4 in regulating tumor stemness and dormancy, positioning it as a potential therapeutic target for metastatic and refractory cancers.

Deep learning for endometrial cancer subtyping and predicting tumor mutational burden from histopathological slides

Endometrial cancer (EC) diagnosis traditionally relies on tumor morphology and nuclear grade, but personalized therapy demands a deeper understanding of tumor mutational burden (TMB), i.e., a key biomarker for immune checkpoint inhibition and immunotherapy response. Traditional TMB prediction methods, such as sequencing exomes or whole genomes, are costly and often unavailable in clinical settings. We present the first TR-MAMIL deep learning framework to predict TMB status and classify the EC cancer subtype directly from H&E-stained WSIs, enabling effective personalized immunotherapy planning and prognostic refinement of EC patients. Our models were evaluated on a large dataset from The Cancer Genome Atlas. TR-MAMIL performed exceptionally well in classifying aggressive and non-aggressive EC, as well as predicting TMB, outperforming seven state-of-the-art approaches. It also performed well in classifying normal and abnormal p53 mutations in EC using H&E WSIs. Kaplan–Meier analysis further demonstrated TR-MAMIL’s ability to differentiate patients with longer survival in the aggressive EC.

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.

Pathological features of the differentiation landscape in esophageal squamous cell cancer and their correlations with prognosis.

For esophageal squamous cell carcinoma (ESCC), universally accepted pathological criteria for classification by differentiation degree are lacking. Tumor budding, single-cell invasion, and nuclear grade, recognized as prognostic factors in other carcinomas, have rarely been investigated for their correlation with differentiation and prognosis in ESCC. This study aims to determine if pathological findings can predict differentiation degree and prognosis in ESCC. This study reviewed tumor slides from 326 patients who underwent surgery for ESCC between 2007 and 2012. Tumors were evaluated for subtypes, tumor nest size, tumor stroma, and nuclear grade (nuclear diameter and mitosis) across different differentiation groups. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, with group differences assessed using the stratified log-rank test and Cox proportional hazards model. The mean values of tumor budding invasion margins in well, moderately, and poorly differentiated groups were 25.3%, 30.7%, and 36.3%, respectively. Mean tumor budding/10HPFs were 8.0, 10.3, and 13.0, respectively. Well-differentiated tumors showed more keratinizing subtypes, smaller tumor budding invasion margins, more Grade 1 tumor budding (0-4 cells), absence of single-cell invasion, larger nuclear diameter (≥5 lymphocytes), higher mitotic counts, more submucosal invasion, and less lymphovascular invasion. Conversely, poorly differentiated tumors exhibited opposite characteristics. Multivariate analyses identified the nuclear diameter as independent prognostic factors for OS and DFS. Pathological features can stratify the differentiation landscape in ESCC patients. The nuclear diameter (4 lymphocytes) can help predict prognosis in ESCC than other pathological features. We first time report the mean values of tumor budding invasion margins and tumor budding/10HPF in well, moderately, and poorly differentiated groups for esophageal squamous cell carcinoma. The landscape of well differentiation was depicted with more keratinizing subtypes, smaller tumor budding invasion margins, more Grade 1 tumor budding (0-4 cells), absence of single-cell invasion, larger nuclear diameter (≥5 lymphocytes), higher mitotic counts, and less lymphovascular invasion. The nuclear diameter as independent prognostic factors for prognosis. The findings indicate that pathological features can stratify the differentiation landscape in ESCC patients and offer novel insight into definition of well or moderately differentiation.

Clinical and prognostic effects of microvascular density and FOXP3 positive T cells in breast cancer

There are conflicting data regarding the prognostic effect of microvascular density (MVD) in breast cancer and its molecular subtypes. It is thought that high levels of FOXP3 + T cells in breast cancer are associated with poor prognosis. However, data regarding FOXP3 show significant variability in the literature. In our study, we aim to measure MVD and FOXP3 + T cells in breast cancer cases and investigate their relationship with each other and their effects on breast cancer patients’ clinical and prognostic features. In our study, the results of 207 female breast cancer patients whose excisional tumoral tissue was obtained are presented. The study evaluated the findings under a light microscope using antibodies against CD34 for measuring MVD and FOXP3 for measuring FOXP3-positive T cells. CD34 ≥ 17 was categorized as high MVD, and CD34 < 17 was classified as low MVD. FOXP3 + cell count ≥ 20/mm2 was categorized as high FOXP3 positivity and < 20/mm2 as low FOXP3 positivity. The SPSS program (version 22) was used to evaluate the results statistically, and p < 0.05 was considered significant. The median age was 54.0 (27–86) years, and the median follow-up period was 60.0 (IQR: 42.6–86.5) months. In the high MVD group, a higher progesterone receptor (PR) positivity rate was detected (p = 0.035). High FOXP3 positivity was significantly associated with high nuclear grade (p = 0.003). High FOXP3 positivity was significantly associated with PR negativity and high Ki67 values ​​(p = 0.009, p = 0.012, respectively). No statistically significant correlation was found between MVD elevation and FOXP3 positivity (r = 0.063, p = 0.36). A weakly significant positive correlation was detected between high Ki67 and FOXP3 positivity (r = 0.0146, p = 0.04). A weak inverse correlation was detected between high FOXP3 positivity and PR percentage values ​​(r=-0.182, p = 0.01). While there was no significant difference in disease-free survival in cases with high MVD and high FOXP3 + T cells compared to groups with low levels, the results were not mature enough because the median values ​​in overall survival could not be reached. A significant correlation was found between high FOXP3 positivity and some aggressive tumor features; no effect on survival was detected. In contrast to literature data on luminal A breast cancer, high MVD in the luminal B (HER2-) subgroup was associated with a lower risk of recurrence. Our study is the first in the literature to evaluate the relationship between MVD measured using CD34 and FOXP3 positive T cells in breast cancer. Our study found no correlation between MVD and FOXP3 positivity, while literature data show significant correlations in some other cancers.

Clinicopathological characteristics of Japanese patients with breast cancer and MET exon 14 skipping alterations.

In non-small cell lung cancer, alterations in mesenchymal-epithelial transition (MET) have been recognized as novel therapeutic targets. In particular, the MET exon 14 skipping mutation (METex14s) is a rare oncogenic driver. Targeted therapy with MET tyrosine kinase inhibitors has recently been approved for this mutation. However, c-MET expression and METex14s frequency and their clinicopathological effects in Japanese patients with breast cancer (BC) remain unknown. Tissue microarray-based immunohistochemistry (IHC) was performed to measure c-MET expression in 930 patients with BC (808 with invasive and 122 with noninvasive BC). Reverse transcription polymerase chain reaction was performed to analyse METex14s in patients exhibiting c-MET expression. Clinicopathological characteristics, including patient prognosis based on c-MET expression and METex14s, were elucidated. IHC staining revealed c-MET expression in 91/930 (9.7%) patients. Notably, IHC expression was frequently observed in apocrine carcinomas (11/26 cases). Among the c-MET IHC-positive cases, METex14s frequency was 25.9% (14/54 cases) in invasive BC and 54.1% (20/37 cases) in noninvasive BC. Furthermore, 4/11 informative noninvasive and invasive BC cases with apocrine differentiation carried METex14s. The nuclear grade was significantly higher in the METex14s-positive group among invasive BC with c-met IHC expression. Furthermore, patients' age and negative rate for PgR IHC was significantly lower in the METex14s-positive group among noninvasive BC. Regarding the factors associated with patient outcomes, both c-MET IHC staining and METex14s expression did not affect survival, regardless of the hormone receptor status. High c-MET expression and METex14s are common in apocrine carcinoma.

Correlation of sonographic features with prognostic factors in ductal carcinoma in situ of the breast: an exploratory study using ultrasound and shear wave elastography

ObjectiveDuctal carcinoma in situ (DCIS) of the breast has a wide disease spectrum with risks of progression to invasive cancer linked to pathological factors. High-grade histology, large tumor volume, and comedonecrosis are adverse prognostic factors. This study explores the correlation between conventional ultrasound (Con-US) and shears wave elastography (SWE) features with DCIS prognostic factors and evaluates their predictive efficacy.MethodsA retrospective analysis was conducted on clinical data, Con-US, and SWE imaging features of 83 DCIS patients who underwent surgical resection between June 2018 and December 2022. Binary logistic regression analysis was performed to explore the relationship between sonogram indices and pathological prognostic factors.ResultsThe results revealed that microcalcification observed on Con-US was an independent risk factor for high-grade DCIS and comedonecrosis [odds ratio (OR): 5.316 and 4.512]. In SWE analysis, the Emax value was significantly different between the non-high-grade and high-grade DCIS groups(P = 0.006), with an Emax value greater than 75.03 kPa identified as an independent risk factor for high-grade DCIS [OR:1.022, the area under the curve (AUC): 0.682, 95% confidence interval (CI): 0.555–0.808]. Additionally, the Ecolor, Emax, Emean, and Emean SD values were statistically different between the groups with and without comedonecrosis (P = 0.049, 0.006, 0.012, 0.022), with an Emean value exceeding 30.45 kPa identified as an independent risk factor for comedonecrosis (OR:1.025, AUC:0.708, 95% CI:0.562–0.854). Furthermore, combining microcalcification on Con-US with specific SWE indicators demonstrated an improved predictive specificity for high-grade DCIS and comedonecrosis (0.902 and 0.889, respectively). No significant difference was found in other indexes on SWE.ConclusionsThe microcalcification signs on Con-US, Emax and Emean values on SWE analysis are associated with the high nuclear grade and comedonecrosis of DCIS, the combination of Con-US and SWE can improve the predictive specificity of DCIS-related prognostic factors.

Comparison of Phacoemulsification and Aspiration Parameters in Cataract Surgery: Metal Tip vs. Hybrid Tip

Various tips are available for phacoemulsification in cataract surgery. Evidence-based data can inform ophthalmologists, especially inexperienced ones, on tip selection. We retrospectively evaluated the energy efficiency and other parameters of two ultrasonic phacoemulsification and aspiration tips across different nuclear hardness grades in 342 cataract patients (342 eyes) with nuclear hardness grades II to IV. Surgical procedures, ultrasound settings, and instrumentation were standardized. All surgeries were performed by one experienced doctor. We compared the metal INTREPID® Balanced Tip (M-tip) with the INTREPID® Hybrid Tip (P-tip), which has a polymer coating. The M-tip required significantly less total ultrasound time and cumulative dissipated energy (CDE) than the P-tip for grades III and IV, while the P-tip had a shorter aspiration time and less estimated fluid aspirated for grade II. No differences in corneal endothelial cell loss were observed. Lens rupture rates were low: 0.47% for the M-tip and 0.78% for the P-tip. Multiple regression analysis showed that CDE increased with nuclear hardness. These findings suggest that the M-tip is efficient for harder lenses, while the P-tip may be advantageous for softer lenses, informing optimal tip selection in cataract surgery. Further research is suggested to elucidate their clinical significance.

Association of Level III Axillary Lymph Node Positivity with Clinicopathological Characteristics in Breast Cancer

Management of breast cancer has gradually shifted from era of radical surgery to present days of multi-modality management and conservatism. While complete axillary dissection is common for node-positive cases, less invasive approaches like sentinel node biopsy are often sufficient for clinically node-negative cases. However, these findings may not apply to all populations, particularly in India where advanced disease presentation is common. The objective of this study is to assess Level III Axillary Lymph Node Positivity with clinicopathological characteristics in Breast cancer. This was a hospital based retrospective observational study on breast cancer patients conducted in single institute from 2016 to 2022. A total of 70 patients with operable breast cancers, who underwent primary tumour resection and complete axillary lymph node dissection, including level III were included in the study. Patients with inoperable and metastatic disease were excluded. Final histopathological examination data was collected and analysed. Most patients (92.9%) underwent Modified Radical Mastectomy, with Infiltrating Ductal Carcinoma (IDC) being the most common histology (90%). Factors significantly associated with level III lymph node positivity included tumour size &gt;4.5cm, nuclear grade III, pathological N3 stage and extra nodal extension. The study found no significant correlation with other factors like age, tumour laterality, location, hormone receptor status, HER2 status, or LVSI. These findings may help predict level III lymph node involvement in breast cancer patients. All these predictive factors should be considered during the axillary dissection.

Fabrication of gas metal arc-welded nuclear grade steel pipe: An insight on microstructural and mechanical properties

This study investigates the use of Gas Metal Arc Welding (GMAW) to butt weld AISI 347 pipes. Microstructural analysis revealed the presence of columnar, equiaxed dendrites, and niobium carbide (NbC). Niobium carbide could effectively prevent intergranular defects by inhibiting chromium and carbon precipitation. X-ray diffraction (XRD) confirmed the presence of austenite and δ-ferrite phases, with δ-ferrite content between 3–8% to prevent hot cracking. Welded samples exhibited superior mechanical strength compared to the base metal (BM), attributed to microstructural and mechanical properties of GMAW-welded AISI 347 pipes, offering valuable guidance for industries involved in nuclear and aerospace application.

PATH-67. THE ROLE OF STATUS OF HER-2, ESTROGEN-RECEPTOR, BRCA 1, AND BRCA 2, IN THE INCIDENCE OF BRAIN METASTASIS IN BREAST CANCER

Abstract Breast cancer (BC) is the most diagnosed tumor in women and the second-leading cause of brain metastasis (BM), with a prevalence ranging from 10-36%. According to the Epidemiological Strategy and Medical Economics research program, advanced BC patients face an estimated 25% risk of developing BM within 2-3 years after the initial diagnosis. The frequency of BM is significantly increased by the primary tumor profile, including larger tumors, higher nuclear grade, HER-2 positivity, estrogen-receptor negativity, and triple-negative status. A gap remains in the classification of the BM site relative to primary tumor biomarkers, and the absence of multimodality treatment methodologies poses challenges to survival rates and quality of life in BC patients. This retrospective cross-sectional study at Aga Khan University Hospital identified 52 cases of brain metastasis secondary to breast cancer over a 10-year period. The median age of patients was 55 years, ranging from 32 to 78 years. Primary breast tumors were predominantly high-grade ductal carcinomas (65%), followed by lobular carcinomas (25%) and other rare histological types (10%). Secondary brain metastases were primarily located in the cerebrum (60%), cerebellum (25%), and brainstem (15%). Tumor profiles indicated a significant correlation between HER-2 positivity and the development of brain metastasis, with 70% of HER-2 positive patients presenting with extensive brain metastasis. Tumor progression varied, with a median time to brain metastasis of 2.5 years from the initial breast cancer diagnosis. Despite aggressive multimodality treatments, including surgery, radiation, and chemotherapy, the overall prognosis remained poor. The study found that early detection of HER-2 positive and triple-negative tumors could potentially delay the progression of brain metastasis through targeted therapies. Mortality rates in this cohort were high, with a median survival of 8 months following the diagnosis of brain metastasis. These findings underscore the need for improved diagnostic, preventive, and therapeutic strategies to manage brain metastasis in breast cancer patients.

Primary Tumor Characteristics and Immunohistochemical Profile of Renal Cell Carcinoma in Serous Fluid Cytology

IntroductionRenal cell carcinoma (RCC) involves serosal surfaces in 2-3% of cases, and thus few papers describe serous fluid cytology (SFC) involvement by RCC. This diagnosis is challenging, given its rarity, non-descript cytomorphologic features and infrequent expression of widely used epithelial markers MOC31 and BerEP4. We describe our institutional experience with RCC in SFC specimens. MethodsOur institutional laboratory information system was queried for SFC specimens from patients with RCC between 2013-2023. Cases signed out as “Suspicious for Malignant Cells” and “Positive for Malignant Cells” were included. Patient demographics, immunohistochemical results, primary tumor characteristics, and molecular data were recorded. ResultsSixty-one (61) cases, 50 pleural and 11 peritoneal fluid specimens were identified. Fifty (50) were signed out as positive for malignancy and 11 were signed out as suspicious for malignancy. MOC31 and BerEP4 were positive in 59% and 55% of cases, respectively. PAX-8, CA9, CD10, and RCC were positive in 85%, 82%, 73% and 29% of cases, respectively.Primary tumor histologic subtypes included 39 clear cell, six (6) papillary, one (1) chromophobe, and 15 were not further subclassified. Fifty-nine percent (59%) of cases had a nuclear grade of 4, and 37% had sarcomatoid or rhabdoid differentiation. Seventy-one percent (71%) of cases had stage 3 or 4 disease. ConclusionsRCC metastasis to serosal surfaces is more likely to be seen in patients with higher disease stage, high nuclear grade, and sarcomatoid or rhabdoid differentiation. MOC31 and BerEP4 performed poorly in this setting. We recommend the addition of cytokeratins, PAX-8, CD10, and CA-9 to confirm metastatic involvement.

Scinderin Promotes Hydrogen Peroxide-induced Lens Epithelial Cell Injury in Age-related Cataract.

Scinderin (SCIN) is a calcium-dependent protein implicated in cell growth and apoptosis by regulating actin cleavage and capping. In this study, we investigated the role of SCIN in hydrogen peroxide-induced lens epithelial cell (LEC) injury related to age-related cataract (ARC). Anterior lens capsules from ARC patients were collected to examine SCIN expression levels. Immortalized human LEC cell line SRA01/04 and lens capsules freshly isolated from mice were induced by H2O2 to mimic the oxidative stress in ARC. The role of SCIN was investigated by gain-of-function (overexpression) and loss-offunction (knockdown) experiments. Flow cytometry (FCM) and Western-blot (WB) assays were performed to investigate the effect of SCIN on apoptosis. The oxidative stress (OS) was examined by detecting malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) activity. The interaction between SCIN mRNA and miR-489-3p was predicted by StarBase and miRDB databases and validated by luciferase reporter activity assay. SCIN was significantly elevated in cataract samples, and the expression levels were positively correlated with the nuclear sclerosis grades. SCIN overexpression promoted OS and apoptosis in H2O2-induced SRA01/04 cells, while SCIN silencing showed the opposite effect. We further showed that miR-489-3p was a negative regulator of SCIN. miR-489-3p overexpression suppressed apoptosis and OS in H2O2-induced SRA01/04 cells by targeting SCIN. Our study identified SCIN as an upregulated gene in ARC, which is negatively regulated by miR-489-3p. Targeting miR-489-3p/SCIN axis could attenuate OS-induced apoptosis in LECs.

Determination of trace analytes in nuclear grade Calcium Metal Samples by Axially Viewed Inductively Coupled Plasma – Atomic Emission Spectrometric technique

An Inductively Coupled Plasma – Atomic Emission Spectrometric (ICP-AES) method has been developed for the direct determination of 19 analytes namely, Al, B, Be, Cd, Co, Cr, Cu, Fe, Li, Mg, Mo, Mn, Ni, Pb, Pd, Si, Ta, V and W at trace concentration levels in calcium matrix. In nuclear industry, quality control and assurance of nuclear fuels and associated materials for trace metallic impurity contents form an integral part of the system for the smooth functioning of the reactor for the stipulated time span. In this context, it was required to determine trace analytes in nuclear grade Calcium which is used as a reducing agent for the production of U, Th, Pu, etc. in nuclear industry. Using axial ICP-AES, initially calibration curve for Ca with 396.847nm analytical line was obtained. Systematic studies were carried out to identify various analytical wavelengths of the analyte elements which are almost free from Ca, being the main matrix and calibration curves were obtained. For all analytes and Ca, detection limits and sensitivity values were calculated. To validate the method, three synthetic samples with analyte contents in the range of 0.1 - 5 g/mL and Ca at 1 mg/mL were analyzed, the % recovery being in the range of 80-120% with precision better than 5% RSD. The method was found to be useful for the direct determination of the elements of interest in calcium matrix and was applied for the analysis of two nuclear grade real life calcium metal samples.

Impact of the CPS-EG score as a new prognostic biomarker in triple-negative breast cancer patients who received neoadjuvant chemotherapy

BackgroundThis study aimed to establish risk groups on the basis of CPS-EG scores, independent of pCR status, in triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT) to identify the prognostic impact of the CPS-EG score.MethodsPatient characteristics included age, menopausal status, clinical stage, pathological stage, estrogen receptor (ER) expression, nuclear grade, Ki-67 proliferation index, residual cancer burden (RCB) score, HER2 status, and other tumor characteristics. The CPS-EG scoring system included clinical stage, pathological stage, ER status, and grade. Patients were divided into two groups on the basis of their CPS-EG scores ≤ 3 and > 3.ResultsA total of 148 patients who were diagnosed with TNBC and treated with NACT were included in the study. A total of 52.0% of the patients had a CPS-EG score of ≤ 3, whereas 48.0% had a score of > 3. The rate of patients who achieved pCR was 29.7% (n = 44). CPS-EG score (HR: 2.331; 95%CI; 1.179–4.608; p = 0.015), pCR (HR: 0.348; 95%CI; 0.144–0.844; p = 0.019), pre-treatment mKi-67 proliferation index (HR: 0.467; 95%CI; 0.251–0.871; p = 0.017), and RCB score (HR: 0.401; 95%CI; 0.174–0.923; p = 0.032) were identified as significant prognostic factors for 5-year DFS. For 5-year OS, significant prognostic factors were CPS-EG score (HR: 2.30; 95%CI; 1.036–4.799; p = 0.040) and pre-treatment mKi-67 proliferation index (HR: 0.484; 95%CI; 0.246–0.954; p = 0.036).ConclusionsThe CPS-EG score, pre-treatment mKi-67 level, and the pCR and RCB score were practical prognostic markers for long-term survival. Conversely, the prognostic significance of pCR status was diminished, particularly in predicting OS. These findings underscore the importance of not only post-treatment pathological staging but also the initial tumor stage and biological characteristics of the tumor in predicting ultimate survival outcomes following neoadjuvant chemotherapy in TNBC patients.

Clinical characteristics of male patients with breast cancer in the Latino population.

Breast cancer is the most prevalent cancer type in Mexico, with male breast cancer accounting for only 1% of all breast cancer cases. A limited number of studies have described the clinical-pathological profiles of males with breast cancer in low- and middle-income countries. This study presents an analysis of patients with breast cancer seen at three different institutions in México. A retrospective review of the medical records was performed to analyze the clinical and pathological characteristics of 49 men diagnosed with breast cancer and their overall survival. The mean age at diagnosis was 64.65years. A significant proportion of patients presented at diagnosis with stage IV disease (n = 11, 22.45%), had triple-negative subtype (n = 6, 12.24%), and nuclear grade III (n = 20, 40.8%). Primary endocrine resistance was observed in 10 patients (31.25%). Genetic analysis was performed on 24 patients (48.9%), revealing a germline BRCA pathogenic variant in 8.33%. Our findings described the clinical and pathological profile of breast cancer in a male cohort in Mexico, with a significantly high proportion of advanced disease, triple-negative subtype, nuclear grade III, and endocrine resistance. Further comprehensive studies, including research into somatic mutations, are needed.

Potentials of pretreatment [18F]FDG PET/CT for non-invasive prediction of the tumor unfavorable pathological indices and microenvironment in NSCLC

PurposeTo investigate pretreatment [18F]FDG PET/CT in predicting tumor pathological features and microenvironment.MethodologyFifty-one patients with histo-pathologically proven non-small cell lung cancer (NSCLC) underwent pretreatment [18F]FDG PET/CT, and their clinicopathological data were collected. PET-derived biomarkers (SUVmax, mean, MTV, and TLG), consolidation-to-tumor ratio (CTR), and histopathological data (tumor grade, differentiation, tumor histological subtype, tumor-infiltrating lymphocytes (TILs), degree of desmoplasia, degree of necrosis, tumor budding, and nuclear grade), as well as a proposed risk stratification pathological scoring system, were all assessed.ResultsA CTR cut-off point of 0.34 was able to discriminate between low- and high-grade tumors with a sensitivity and specificity of 75.9% and 68.2%, respectively (p = 0.012). Low CTR was significantly associated with the tumor pathological subtype “adenocarcinoma,” low nuclear grade, negative tumor necrosis, and low pathological scores, respectively (p < 0.05). No significant associations were observed for CTR with tumor budding score, desmoplasia score, or TILs% (p-values > 0.05). High SUVmax (> 12.64) and high SUVmean (> 4.28) values were significantly associated with SCC tumors (p = 0.023 and 0.04, respectively). SUVmean was significantly associated with cytological differentiation (p = 0.023). A statistical trend was noted for SUVmax concerning nuclear grade and desmoplasia scores (p = 0.068 and 0.061, respectively). No statistically significant associations were revealed for MTV and TLG concerning different pathological features (p-values > 0.05). Primary lung tumors positive for desmoplasia revealed higher metabolic activity regarding SUVmax, with a statistical trend observed (p = 0.072). No statistically significant associations were observed concerning other metabolic parameters (p-values > 0.05).ConclusionPET/CT-derived biomarkers appear promising for predicting tumor unfavorable pathological features and microenvironment in NSCLC.