Histological Subtype Research Articles

A Rare Case Study of Mucinous Intestinal-Type Adenocarcinoma in the Maxillary Sinus

Maxillary sinus cancers, constituting a minority of head and neck malignancies, exhibit a diverse range of histological subtypes, each necessitating a nuanced approach to diagnosis and treatment. Within this spectrum, mucinous adenocarcinoma stands as an exceedingly rare variant, and this case report aims to provide a thorough examination of its clinical, radiological, and histopathological dimensions within the context of maxillary sinus malignancies. Surgical resection is considered as treatment of choice for this kind of tumor. A 68-year-old male underwent total maxillectomy using Weber-Ferguson incision for maxillary sinus tumor in our department. The pathological report of tumor was revealed as mucinous type adenocarcinoma. The specimen was observed thoroughly, and based on immunohistochemical findings, diagnosed as mucinous type adenocarcinoma. So, we present a rare case of mucinous type adenocarcinoma arising from the maxillary sinus.

Investigation of Herpes Viridea and Parvovirus B19 Frequencies in Lymphopenic Malignant Patients Receiving Chemotherapy

Background/Aims: In this study, we aimed to investigate the incidence of Epstein-Barr virus (EBV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Parvovirus B19 viral infections in patients diagnosed with cancer receiving chemotherapy in our clinic. Methods: In this study, 138 lymphopenic patients who were hospitalized and received chemotherapy at Medical Oncology Clinic between April 2018 and July 2018 were evaluated prospectively. Cancer diagnoses of the patients included in the study were lung, esophagus, prostate, breast, pancreatic, colorectal, stomach, brain and nervous system, ovarian and others (ewing sarcoma, hepatocellular carcinoma, larynx carcinoma, bladder carcinoma, malignant mesenchymal tumor, multiple myeloma, primary unknown lymphoma, metastatic carcinoma of unknown primary, renal cell carcinoma, cervical carcinoma, testicular carcinoma) cancers. The patients were at various stages of cancer, had various histological subtypes, and were receiving various chemotherapies. The % frequency of EBV, HSV, CMV and Parvovirus B19 in serum samples were determined. Results: The mean age of the patients was 58.93 ± 13.28 years, and the mean duration of diagnosis was 2,0 ± 2,2 years. EBV PCR positivity was detected in 9 patients (6.5%), CMV PCR positivity in 12 patients (8.7%), and EBV and CMV (together) PCR positivity in 1 (0,7%) patient. HSV and parvovirus B19 PCR positivitys were not determined in any patients. According to the results of the survival analysis, the average survival time in all lymphopenic patients was 3.71 months. It was observed that 65.21% of all lymphopenic patients die within 12 months following lymphopenia diagnosis. Conclusions: As a result of our study, EBV and CMV PCR positivity rates were determined in all lymphopenic patients receiving chemotherapy (6.5% and 8.7%, respectively). More comprehensive studies are needed to determine the incidence of HSV and parvovirus B19. In addition, lymphopenic patients receiving chemotherapy should be followed up by physicians for viral infections and treated with antiviral therapy in the early stages of infection.

A comprehensive analysis of the expression and prognostic significance of signal transducers and activators of transcription family in gastric cancer patients

Abstract Background Understanding the role of the STAT family in gastric cancer (GC) is essential for developing targeted therapies and improving patient outcomes. However, comprehensive analysis of STAT expression and its prognostic significance in GC is limited. This study aims to address this gap by examining STAT expression in normal and GC tissues and evaluating its prognostic value across clinical subgroups. Methods STAT mRNA expression levels were compared between tumor and normal tissues using fold change analysis. Kaplan–Meier curves assessed the correlation between STAT expression and clinical outcomes, with statistical significance determined by the Log-rank test and hazard ratios (HR) with 95% confidence intervals. Subset analyses evaluated STAT expression across GC subtypes and its prognostic value, including in patients with oncogenic mutations. Results Most STAT family members, except STAT4, showed increased expression in GC tissues compared to normal tissues, consistent across various clinical subgroups, suggesting a role in GC pathogenesis. Kaplan–Meier analysis revealed the prognostic significance of STATs in GC. High STAT1 expression was associated with improved overall survival (OS), first progression (FP), and post-progression survival (PPS), indicating a favorable prognosis. In contrast, elevated STAT5A, STAT5B, and STAT6 expression correlated with poor prognosis. Subgroup analysis highlighted the consistent prognostic value of STATs across different histological subtypes, particularly in intestinal-type GC. Additionally, STAT expression had differential prognostic implications based on HER2 status. HER2-positive GC patients with high STAT expression had worse OS and FP rates, while HER2-negative patients with high STAT1 expression had better survival outcomes. Conclusions This study provides valuable insights into STAT expression patterns and their prognostic significance in GC. The upregulation of STATs, except STAT4, suggests their involvement in GC oncogenesis. Notably, high STAT1 expression is a favorable prognostic marker, while increased STAT5A, STAT5B, and STAT6 expression correlates with poor prognosis. These findings underscore the potential of STATs as prognostic markers in GC, guiding personalized treatment strategies and improving patient outcomes.

Differential expression of metabolic enzymes in testicular germ cell tumors: The impact of glycolytic metabolism in embryonal carcinoma histotype.

Testicular germ cell tumors are the most common solid malignancies in young men, with increasing incidence worldwide. Broadly classified into seminomas and non-seminomas, they exhibit distinct biological behaviors and responses to treatment. Although metabolic reprogramming is an acknowledged cancer hallmark, metabolic pathways in testicular germ cell tumors remain poorly understood. This study investigates the differential expression of metabolic markers (GLUT-1, MCT1, MCT4, LDHA, HIF-1α) and the epigenetic enzyme KDM3A across various testicular germ cell tumor subtypes, aiming to understand how glycolytic metabolism is related to each histotype and how it may impact tumor aggressiveness, correlating with patient outcomes. The study involved 111 testicular germ cell tumor individual tumor components from 90 patients diagnosed and treated at a comprehensive cancer center. Immunohistochemistry was used to ascertain biomarker expression, with a combined score of percentage of stained tumor cells and intensity of staining. In silico analysis of the Cancer Genome Atlas database was performed for additional validation, using cBioPortal. Statistical analyses included Mann-Whitney U, Kruskal-Wallis, and anova tests, with significance set at p<0.05. Significant differences in the expression of metabolic markers across testicular germ cell tumor subtypes were disclosed. Embryonal carcinomas showed significantly higher expression of glycolytic markers (GLUT-1, MCT1, MCT4, LDHA) compared to other histotypes, suggesting heightened glycolytic activity. KDM3A depicted an inverse pattern, being significantly more expressed in seminomas. HIF-1α expression was generally low across all histological subtypes. Testicular germ cell tumors with necrosis showed higher expression of the metabolic players investigated. We highlighted distinct metabolic profiles among testicular germ cell tumor subtypes, particularly the prominent glycolytic activity in embryonal carcinomas, with higher hypoxia and reliance on lactate transport. Metabolic reprogramming in embryonal carcinoma may underlie the high proliferation of this tumor subtype, which frequently discloses necrosis. These findings suggest that targeted agents such as MCT1 inhibitors may be particularly useful for treating testicular germ cell tumors containing high proportion of embryonal carcinoma.

Clinical impact of a subtype of urothelial carcinoma in nonmuscle-invasive bladder cancer.

This study aimed to assess the oncological outcomes of the subtype of urothelial carcinoma (SUC), including divergent differentiation and histologic subtype, in comparison with those of pure urothelial carcinoma (PUC) in nonmuscle-invasive bladder cancer. We retrospectively evaluated patients who were initially treated with transurethral resection of the bladder tumor (TURBT) between March 2005 and August 2020 at a single institution. Patients with PUC and SUC were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). Out of 853 enrolled patients, 783 (91.8%) and 70 (8.2%) had PUC and SUC, respectively. SUC presence was significantly associated with old age, tumor size (≥3cm), higher pT1 rate, high grade, concomitant carcinoma in situ, and lymphovascular invasion. RFS rates after TURBT did not significantly differ between the PUC and SUC groups. With a median follow-up period of 66months (interquartile range, 38-103months), the rates and median time of progression to muscle invasion were 6.9% and 22.5months in the PUC group, and 22.9% and 10.0months in the SUC group. Moreover, the incidence of progression to metastasis was 4.6% and 15.7% in the PUC and SUC groups, respectively. The 5-year PFS rates (64.5% and 81.9%, P< .001) and 5-year OS rates (71.7% and 86.2%, P=.009) were lower in the SUC group than in the PUC group. On multivariate analysis, SUC presence independently predicted progression to muscle invasion and metastasis. At initial TURBT diagnosis, we must pay more attention to higher progression risk of SUC than that of PUC in nonmuscle-invasive bladder cancer.

Non-Invasive miRNA Profiling for Differential Diagnosis and Prognostic Stratification of Testicular Germ Cell Tumors.

Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors. This study aimed to assess the potential of differentially expressed miRNAs in differential diagnosis and prognostication among TGCT patients with various histologic subtypes. Transcriptomic analysis of 134 patients from The Cancer Genome Atlas (TCGA)-TGCT database was conducted. miRNA differential expression analysis among seminomatous, embryonal carcinoma, mixed GCT, and teratoma was performed, followed by ROC curve analysis of the most significantly up- and downregulated miRNAs, respectively. Statistical associations of miRNA expression with AJCC stage were also investigated along with miRNA target network analysis and evaluation of miRNA detection in patients' fluids. Upregulation of seven miRNAs (hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-200a, hsa-mir-200b, hsa-mir-203b, hsa-mir-375, hsa-mir-582) and downregulation of seven additional miRNAs (hsa-mir-105-1, hsa-mir-105-2, hsa-mir-4433a, hsa-mir-548x, hsa-mir-5708, hsa-mir-6715a, hsa-mir-767) were identified. miRNAs displayed a high sensitivity/specificity of 0.94/1.0 (AUC = 0.98) for the upregulated and 0.97/0.94 (AUC = 0.96) for the downregulated signature. Deregulated expression of these miRNAs was significantly associated with AJCC stage and distant organ metastasis (p < 0.001), overall supporting their prognostic strength. Both signatures were detectable in body fluids, particularly urine. miRNA target network analysis supported the functional role of these miRNAs in the regulation of cancer-related processes such as cell proliferation via deregulation of pivotal oncogenes. These findings support the clinical value of two novel miRNA signatures in differential diagnosis and prognostic stratification of various histologic subtypes of TGCT, with potential treatment implications.

Immunological differences between monophasic and biphasic synovial sarcoma with implications for immunotherapy

Synovial sarcoma is an aggressive soft-tissue cancer that shows limited responses to current immunotherapeutic approaches using immune checkpoint blockade or adoptive cell therapy. To improve immunotherapy for this cancer, understanding how the immune cells in the tumor microenvironment associate with histological subtype, disease progression and current therapies is vital. To evaluate the immune infiltrate in synovial sarcoma in relation to histological subtype, disease progression and in response to cytotoxic treatment, we performed immunodetection of T cells, CD68+ myeloid cells, endothelial cells and keratin on a series of 41 synovial sarcoma patients at various stages of disease. The immune composition of synovial sarcoma was dominated by CD68+ myeloid cells of which a substantial part was of the CD163+ immunosuppressive phenotype, which increased after chemotherapy or radiotherapy. Biphasic synovial sarcomas were more densely infiltrated by both T cells and myeloid cells than monophasic synovial sarcomas. In these tumors, the immune and endothelial cells were mostly located within the stromal like, spindle cell compartment and excluded from the epithelial compartment, greatly resembling the spatial organization of healthy epithelium such as in the colon. Together these data demonstrate that biphasic synovial sarcoma is immunologically different from monophasic synovial sarcoma and might be more susceptible to immunotherapies such as adoptive T-cell therapy. Finally, T-cell infiltration in primary synovial sarcoma was associated with prolonged overall survival of patients which suggests that intratumoral T cells may demonstrate anti-tumor activity.

Reproductive factors and risk of epithelial ovarian cancer: results from the Asia Cohort Consortium.

There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women. This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for age, parity and cohort. After a mean = 17.0 years (SD = 6.3) of follow-up, 674 incident invasive EOC cases were identified among 325,626 women. In multivariable adjusted models we observed an inverse association with parity (5+ children vs. 0, HR = 0.44, 95% CI = 0.28-0.68, Ptrend < 0.001), and a positive association with increasing menopausal age (55+ years vs. <45, HR = 1.77, 95% CI = 1.05-3.01, Ptrend = 0.02) for risk of all EOC. In this large study of Asian women we identified an inverse association with parity and a positive association with higher menopausal age in relation to EOC risk. Further work is needed to understand EOC risk factors for rare histologic subtypes that occur more frequently in Asian populations.

Clinico-pathological factors and [18F]FDG PET/CT metabolic parameters for prediction of progression-free survival in radioiodine refractory differentiated thyroid carcinoma

ObjectiveIdentifying prognostic markers for clinical outcomes is crucial in selecting appropriate treatment options for patients with radioiodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC). The aim of this study was to investigate the prognostic value of clinico-pathological features and semiquantitative [18F]FDG PET/CT metabolic parameters in predicting progression-free survival (PFS) in DTC patients with RAI-R.Patients and methodsThis prospective cohort study included 110 consecutive RAI-R DTC patients who were referred for [18F]FDG PET/CT imaging. The lesion standard uptake values (SUV)s, including SUVmax, SUVmean, SULpeak as well astotal metabolic tumor volume (tMTV)and total lesion glycolysis (tTLG) were measured. Disease progression was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0. PFS curves were plotted using Kaplan–Meier analysis. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for PFS.Results[18F]FDG PET/CT metabolic parameters demonstrate predictive value for PFS in RAI-R DTC patients, with sensitivity ranging from 70.7% to 81% and specificity from 75% to 92.3% (p < 0.001). PFS was significantly worse in patients with SUVmax > 6.39 g/ml, SUVmean > 3.68 g/ml, SULpeak > 3.14 g/ml, tTLG > 4.23 g/ml × cm3, and tMTV > 1.24 cm3. Clinico-pathological factors including age > 55, aggressive variant and follicular histological subtype, extra-thyroidal extension of the primary tumor, stage III – IV disease at initial DTC diagnosis, distant metastases detected on [18F]FDG PET/CT, and metabolic parameters of [18F]FDG PET/CT associated with PFS in univariate analysis (p < 0.01). In multivariate analysis, extra-thyroidal extension (HR: 2.25; 95% CI: 1.22 – 4.16; p = 0.01), distant metastases on [18F]FDG PET/CT (HR: 2.98; 95%CI: 1.62 – 5.5; p < 0.001), and tMTV > 1.24 cm3 (HR: 4.17; 95% CI: 2.02 – 8.6; p < 0.001), were independent prognostic factors for PFS.ConclusionsIn addition to classic clinico-pathological factors, the semiquantitative [18F]FDG PET/CT metabolic parameters can be utilized for dynamic risk stratification for progression in RAI-R DTC patients. Furthermore, extra-thyroidal extension of the primary tumor, distant metastases, and tMTV > 1.24 cm3 are independent prognostic factors for PFS.

Adult Cerebellopontine Angle Medulloblastoma: A Systematic Review of Clinical Features, Management Approaches, and Patient Outcomes.

The aim of this study was to systematically review the existing individual patient data in the literature on adult cerebellopontine angle (CPA) medulloblastoma (MB) and characterize the patient presentation, management strategies used, and oncological outcomes of this rare entity to guide future clinical practice. Following PRISMA guidelines, a systematic review was conducted by searching PubMed, EMBASE, Web of Science, and Cochrane databases from inception to 19 June 2024. Studies regarding adult patients with histologically confirmed MB radiographically confirmed to be located in the CPA were included. Clinical data were synthesized, and predictors of outcomes were evaluated. Twenty-seven studies with 42 adult CPAMB patients were included. The median age was 32 years (range: 19-56). Headaches (81%), cranial neuropathy (90%), cerebellar dysfunction (79%), and nausea/vomiting (50%) were typical presenting features. The predominant histological subtype was the classic variant. Maximal safe surgical resection was performed, most commonly using a retrosigmoid approach, and 60% of cases received a gross total resection. Most patients received adjuvant treatment (93%), typically chemoradiotherapy. The recurrence rate was 11% after a median of 18 months of follow-up. Relatively high survival rates of 96%, 85%, and 85% were observed at 1, 3, and 5 years, respectively. Patients who received adjuvant therapy had significantly better recurrence and greater overall survival outcomes. These results support the consideration of MB in young adult patients presenting with CPA tumors with radiographical features suggestive of hypercellularity and the utilization of a management strategy of maximal safe resection plus post-operative craniospinal irradiation along with chemotherapy to optimally treat these rare patients.

Histologic and immunologic factors associated with response to immune checkpoint inhibitors in advanced sarcoma.

To characterize factors associated with response to immune checkpoint inhibitors (ICIs) in advanced sarcoma. This is a retrospective study with a cohort of 216 patients with advanced sarcoma treated with ICIs between 2016-2023 at Stanford Health Care. Overall survival (OS), progression free survival (PFS), objective response rates per RECIST criteria (ORR), and reason for ICI discontinuation were analyzed across histologic subtypes, ICI regimens, tumor mutational burden (TMB), and PD-L1 expression. The overall ORR in the cohort was 16.7%. The histologic subtypes with the highest ORR were Kaposi sarcoma (KS, 66.7%), alveolar soft part sarcoma (ASPS, 50%), angiosarcoma (AS, 33.3%), myxofibrosarcoma (MFS, 28.6%), and undifferentiated pleomorphic sarcoma (UPS, 27.8%). The subtypes with the lowest ORR were osteosarcoma (0%), synovial sarcoma (SS, 0%), and liposarcoma (LPS, 3.7%). The subtypes with the highest median PFS were KS (median not reached, NR), ASPS (NR), MFS (27.4 months), and UPS (11.3 months). The ORR for sarcomas with PD-L1 ≥ 1% was 27.8% (p=0.02), while the ORR for sarcomas with TMB ≥ 10 mutations per megabase of DNA (mut/MB) was 28.6% (p=0.20). ORR and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the highest ORR and longest PFS while osteosarcoma, SS, and LPS had the lowest ORR and shortest PFS. PD-L1 expression was also associated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs.

Comprehensive analysis of lysine lactylation and its potential biological significance in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a common histological subtype of malignant renal neoplasm. Protein lysine lactylation (Kla) plays a crucial role in tumor metabolic reprogramming. However, little is known regarding the distribution and potential biological functions of Kla in ccRCC. This study aimed to systematically investigate the role of Kla in ccRCC.MethodsA total of 12 ccRCC samples were collected from 6 patients. Western blotting was performed to determine the trend of Kla-modified proteins in ccRCC. Liquid chromatography–tandem mass spectrometry was used to quantitatively analyze Kla in ccRCC. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) network analyses were conducted to clarify the biological functions and interactional relationships of differentially lactylated proteins (DLPs).ResultsIn total, 239 DLPs, including 441 lactylated sites, were identified by comparing ccRCC tissues with adjacent normal tissues. Kla-related enzymes have a higher affinity for alanine than for other amino acid residues in ccRCC. Subcellular localization analysis revealed that most DLPs were localized in the cytoplasm and mitochondria. GO enrichment analysis showed that most of the DLPs were enriched in metabolism-associated biological processes, including the purine ribonucleotide, monocarboxylic acid, ribonucleoside triphosphate, purine nucleoside triphosphate, and ATP metabolic processes. KEGG analysis indicated that most DLPs were also enriched in metabolism-related pathways, including glycolysis, amino acid (valine, leucine, and isoleucine) degradation, pyruvate metabolism, fatty acid degradation, and the citrate cycle. The top 20 hub proteins were screened from the PPI network based on their degree ranks.ConclusionsThis study revealed the role of Kla in ccRCC, which will extend our understanding of the potential molecular mechanisms underlying ccRCC formation and progression. These key Kla-modified proteins may be promising therapeutic targets for the treatment of ccRCC. However, further molecular experiments are required to validate these findings.

Differences in mean age at diagnosis of invasive melanoma for men and women, by anatomic site, thickness, and subtype.

Understanding the factors influencing age at melanoma diagnosis by sex and anatomic site is crucial for developing effective prevention and early detection strategies. While previous research has highlighted sex-based differences in melanoma incidence by age and anatomic distribution, the underlying mechanisms remain unclear. We aimed to investigate sex-specific patterns in melanoma age at diagnosis across different anatomic sites and thickness categories, considering the potential influence of disease progression and detection rates. We conducted a registry-based study to examine mean age at diagnosis of invasive melanoma over two decades for men and women in the US (limited to white race), and Queensland, Australia. Mean age at diagnosis was calculated for men and women according to anatomic site (head/neck, trunk, upper limb, lower limb), and further by Breslow thickness (<1.00 mm, 1.01-2.00 mm, 2.01-4.00 mm, >4.00 mm) and histologic subtype (superficial spreading, nodular, lentigo maligna, 'other' subtypes, and subtype 'not otherwise specified'). Case-listings of all invasive melanoma diagnoses between 1 January 1999 and 31 December 2018 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (9 registries) and from the Queensland Cancer Registry. Sensitivity analyses were performed restricting the data to the most recent 5-year time period (2014-2018). All analyses were conducted between 15 July and 19 August 2024. On average, women were diagnosed with invasive melanoma 3-8 years younger than men. The sex-difference in mean age at diagnosis was observed at all body sites and across most thickness categories in the US White and Queensland populations, but was most marked for thinner melanomas (<1.00 mm) and melanoma of the trunk. Women were significantly younger than men at diagnosis of superficial spreading and nodular melanoma at all body sites in both populations, even within 0.1mm thickness strata. Sex may be a factor that influences melanocytic progression. The consistently younger age of melanoma diagnosis in women compared with men suggests a need for tailored approaches to melanoma control.

Oncogenic Functions of Alternatively Spliced MDM2-ALT2 Isoform in Retroperitoneal Liposarcoma.

Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment, while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated the biological functions of the MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p-AKT, mTOR, p70S6K, MMP2, and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression.

Mesenchymal Stem Cells-Derived Small Extracellular Vesicles and Their Validation as a Promising Treatment for Chondrosarcoma in a 3D Model in Vitro.

Chondrosarcomas (CHS) constitute approximately 20% of all primary malignant bone tumors, characterized by a slow growth rate with initial manifestation of few signs and symptoms. These malignant cartilaginous neoplasms, particularly those with dedifferentiated histological subtypes, pose significant therapeutic challenges, as they exhibit high resistance to both radiation and chemotherapy. Ranging from relatively benign, low-grade tumors (grade I) to aggressive high-grade tumors with the potential for lung metastases and a grim prognosis, there is a critical need for innovative diagnostic and therapeutic approaches, particularly for patients with more aggressive forms. Herein, small extracellular vesicles (sEVs) derived from mesenchymal stem cells are presented as an efficient nanodelivery tool to enhance drug penetration in an in vitro 3D model of CHS. Employing high-pressure homogenization (HPH), we achieved unprecedented encapsulation efficiency of doxorubicin (DXR) in sEVs derived from mesenchymal stem cells (MSC-EVs). Subsequently, a comparative analysis between free DXR and MSC-EVs encapsulated with DXR (DXR-MSC-EVs) was conducted to assess their penetration and uptake efficacy in the 3D model. The results unveiled a higher incidence of necrotic cells and a more pronounced toxic effect with DXR-MSC-EVs compared to DXR alone. This underscores the remarkable ability of MSC-EVs to deliver drugs in complex environments, highlighting their potential application in the treatment of aggressive CHS.

LRP1B mutation is associated with lymph node metastasis in endometrial carcinoma: A clinical next-generation sequencing study.

This study aims to investigate the mutation status and protein expression of low-density lipoprotein receptor-related protein 1B (LRP1B) in endometrial cancer, and analyze its association with lymph node metastasis (LNM) in endometrial cancer. Targeted next-generation sequencing (NGS) was conducted on both tumor tissues and paired blood DNA obtained from 94 endometrial cancer patients, followed by comprehensive analysis. Additionally, immunohistochemistry (IHC) was used to explore the correlation between LRP1B protein expression levels, its gene mutation status, and LNM. LRP1B mutation was observed in 19 patients (20.2%). Our results revealed that LRP1B mutation frequencies were significantly different between endometrial cancer with or without LNM (P = 0.038). Multivariate analysis indicated that LRP1B mutation was a favorable predictor (odds ratio 0.09; 95% confidence interval 0.01-0.95; P = 0.045) for LNM in endometrial cancer. Further analysis revealed that combination of LRP1B mutation with clinical variants (LVSI and histological subtype) yielded a higher area under the curve value of 0.871) and patients harboring LRP1B mutated-type were less likely to develop LNM. On integrated analysis, the concordance between LRP1B NGS and LRP1B IHC was 73.3%. This study utilizes targeted NGS to uncover the relationship between LRP1B mutation and LNM status, contributing to the development of primary prevention and proactive treatment strategies.

Birth characteristics and the risk of childhood brain tumors: A case-control study in Ontario, Canada.

Various birth characteristics may influence healthy childhood development, including the risk of developing childhood brain tumors (CBTs). In this study, we aimed to investigate the association between delivery methods, obstetric history, and birth anthropometrics with the risk of CBTs. This study used data from the Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) which included children 0-15 years of age and newly diagnosed with CBTs from 1997 to 2003. Multivariable logistic regressions were performed to explore the association between delivery methods, obstetric history, and birth anthropometric variables, with subsequent CBT development. Models were adjusted for maternal and index child characteristics, and stratified by histology where sample size permitted. The use of assistive instruments (forceps or suction) during childbirth was significantly associated with overall CBTs (OR 1.84, 95% CI 1.30-2.61) and non-glial tumors (OR 2.57, 95% CI 1.60-4.13). Compared to first-born children, those second-born or greater had a lower risk of overall CBT development (OR 0.74, 95% CI 0.55-0.98), and glial histological subtype. All other birth characteristic variables explored were not associated with CBTs. The use of assistive devices such as forceps or suction during vaginal delivery carries potential risks, including increased risk of CBT development. There is an inverse association between birth order and CBTs, and future studies examining early childhood common infection may be warranted.

Pulmonary Adenocarcinoma Updates: Histology, Cytology, and Grading.

Adenocarcinomas are the most common histologic subtype of lung cancer, and exist within a widely divergent clinical, radiologic, molecular, and histologic spectrum. There is a strong association between histologic patterns and prognosis that served as the basis for a recently described grading system. As the study of molecular pathology rapidly evolves, all targetable mutations so far have been found in adenocarcinomas, thus requiring accurate diagnosis and classification for triage of molecular alterations and adequate therapy. To discuss the rationale for adenocarcinoma classifications within the 2021 5th edition of the World Health Organization, with a focus on nonmucinous tumors, including tumor grading and biopsy/cytology diagnosis. PubMed search. A grading system for adenocarcinoma has improved prognostic impact of the classification of pulmonary adenocarcinoma. An accurate diagnosis of adenocarcinoma in small biopsy material is important for tissue triage for molecular studies and ultimately for patient management and treatment.

The Prognostic Significance of Tumor Budding and Tumor-Infiltrating Lymphocytes in Patients Diagnosed With Malignant Melanoma.

The tumor microenvironment plays a critical role in malignant melanoma, influencing progression and patient outcomes, particularly through tumor budding (TB) and tumor-infiltrating lymphocytes (TILs). Despite the importance of TB, its detailed impact still needs to be explored, especially its interaction with TILs. This study evaluates the prognostic significance of TB and TILs in malignant melanoma, assessing their potential as indicators for disease progression and survival. Conducted at Akdeniz University, the research included 92 patients diagnosed between 2014 and 2021. TB was evaluated according to the International Tumor Budding Consensus Conference guidelines, and TILs were assessed by the International Immuno-Oncology Biomarker Working Group standards. The analysis revealed significant correlations between TB and the level of anatomic invasion, Breslow thickness, satellite nodules, lymph node metastasis, distant metastasis, and stage (P < 0.05). A notable inverse relationship between TB and intratumoral TILs suggested their different roles in tumor progression. Tumor subtype, level of anatomic invasion, satellite nodules, lymphovascular invasion, lymph node metastasis, distant metastasis, stage, TILs, and TB were significant risk factors associated with poor prognosis (P < 0.005). Multivariate Cox regression identified histologic subtype and TB >10 as independent prognostic factors, underscoring the need for further research to integrate TB and TILs into clinical practice for better patient management and treatment planning.

Integrated Molecular Characterization of Sarcomatoid Hepatocellular Carcinoma.

Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial-mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1-5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.