Clinical Pathological Features Research Articles

Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer

BackgroundMounting evidence underline the relevance of macromolecular complexes in cancer. Integrins frequently recruit ion channels and transporters within complexes which behave as signaling hubs. A complex composed by β1 integrin, hERG1 K+ channel, the neonatal form of the Na+ channel NaV 1.5 (nNaV1.5) and the Na+/H+ antiporter NHE1 (NHE1/hERG1/β1/nNaV1.5 complex) has been recently described to be expressed and regulate relevant cancer related behaviors in Breast Cancer (BCa) cells.MethodsWe analyzed the expression and impact on outcome of the genes encoding the four proteins forming the NHE1/hERG1/β1/nNaV1.5 complex (SLC9A1, KCNH2, ITGB1 and SCN5A) in public datasets. The corresponding proteins were also evaluated by immunohistochemistry and their expression was correlated with clinic-pathological and molecular characteristics and patients’ survival.ResultsThe expression of KCNH2 and SCN5A was significantly correlated in primary BCa as occurs in the heart, although with a broader distribution, forming a functional network which also included ITGB1 and SLC9A1. The co-expression proteins emerged from the immunohistochemistry analysis. Interestingly, hERG1, nNav1.5 and the hERG1/β1 integrin complex associated with several clinical features, including molecular subtype and hormone receptor status. Moreover, hERG1 and the combination of hERG1 and nNav1.5 had impact on prognosis, contributing to identifying a group of patients with worse prognosis.ConclusionshERG1 and nNav1.5 channels along with β1 integrins and the NHE1 antiporter are co-expressed in BCa both at gene and protein levels, assembling into a macromolecular complex. The NHE1/hERG1/β1/nNaV1.5 complex can be considered a novel biomarker and potential target for therapy for BCa patients.

P0447 Accurate, rapid and economical diagnosis of chronic enteropathy associated with SLCO2A1 gene and the analysis of its clinical pathological features

Abstract Background Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a rare intestinal disease caused by loss of protein function due to mutations in the SLCO2A1 gene. Currently, the clinical features of this disease are poorly understood, and diagnosis of lesions in the small intestine is challenging with limited methods, relying heavily on costly genetic sequencing. Therefore, this study aims to elucidate the clinical characteristics of Chinese CEAS patients and explore the diagnostic value of immunohistochemistry of biopsy tissues from duodenum, terminal ileum or colon site. Methods A retrospective analysis was conducted on 10 cases of CEAS admitted to the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, from January 2015 to May 2024. Data including demographic information, clinical manifestations, laboratory and imaging results, pathological findings, genetic testing, and immunohistochemistry (IHC) results were analyzed. Results Of the 10 patients, 4 were male and 6 were female, the average age at onset was 25 years (IQR 17-36), and the average age at diagnosis was 41 years (IQR 39-44), with an interval of about 16 years from onset to diagnosis. Two patients had concurrent primary hypertrophic osteoarthropathy (PHO), both of whom were male. All patients had small intestine involvement, with the most common endoscopic findings being multiple strictures and superficial ulcers of the small intestine. Pathological findings indicated nonspecific chronic inflammation limited to the mucosa and submucosa. Five patients underwent surgical treatment, all involving partial small bowel resection. Genetic sequencing results indicated SLCO2A1 gene mutations in all 10 patients, with 7 patients having homozygous mutations and 3 having heterozygous mutations. Immunohistochemistry for SLCO2A1 protein on pathological specimens from the affected small intestine showed loss of SLCO2A1 expression in 9 patients and markedly reduced expression in 1 patient, with focal loss in specific vascular regions. Further immunohistochemistry of non-affected sites, including the descending duodenum and terminal ileum, also showed decreased or absent SLCO2A1 expression, consistent with findings in the affected areas. Conclusion CEAS is characterized by multiple small intestinal strictures, with a minority of patients also presenting with hypertrophic osteoarthropathy, which is more common in males. Immunosuppressants and biologics generally show poor efficacy. Historically, CEAS has been difficult to diagnose with a prolonged time to diagnosis, and genetic testing is costly and time-consuming. Immunohistochemical analysis of SLCO2A1 protein, regardless of whether the tissue is from affected or non-affected areas, can aid in early diagnosis.

Age-Related Variations in Clinical, Histological, and Genetic Characteristics in Multiple and Familial Melanomas: A Study of 333 Patients

Background/Objectives: Melanoma is an aggressive cutaneous malignancy with a rising incidence. While most cases are sporadic, 5–10% are hereditary, especially in patients with multiple or familial melanomas. The aim of this study is to explore the epidemiological, clinical, histological, and genetic features of this class of patients to identify risk factors for better management and surveillance. Methods: Between 2021 and 2024, patients with multiple melanomas or a familial history of melanoma were recruited. Collected data included demographic, clinic-pathologic features, and genetic analyses. Results: Patients >60 years had a higher prevalence of multiple melanomas (>50%, p = 0.0002), while familial melanoma was more common in those <40 years (54.3%). UV exposure increased with age, while sunscreen use decreased (p = 0.0004). Younger patients showed the highest nevi counts (mean: 139.6) and density (p < 0.0001). Dermatologists more frequently detected subsequent melanomas in older patients (>60 years) (p = 0.001). Genetic testing and melanoma subtypes showed no significant age-related differences. Conclusions: melanoma can develop at any age, and early detection through regular screening is crucial. Older patients (>60 years) have a higher prevalence of multiple melanomas, influenced by UV exposure and genetics. Indeed, in our cohort, a history of sun exposure, sunburns, and tanning bed use emerged as key risk factors, particularly among older individuals. Genetic testing showed a 4.3% rate of pathogenic/likely pathogenic variants, mainly in CDKN2A. Family history and nevus burden are significant risk factors, highlighting the need for targeted surveillance in high-risk populations.

P0023 Methionine Restriction Promotes Intestinal Mucosal Repair by Regulating Selenbp1 and Modulating Macrophage Polarization

Abstract Background Intestinal epithelial homeostasis is critical for maintaining gut integrity and function. Methionine is an essential amino acid involved in various cellular processes, and its dietary regulation may impact intestinal injury and repair mechanisms. Selenbp1, an oxidase of the methionine metabolite methanethiol, plays an important role in this process. This study investigates the role of methionine intake and Selenbp1 in colonic injury and epithelial repair. Methods Animal models with radiation-induced intestinal injury were used to assess the effects of methionine restriction and supplementation. Intestinal epithelial-specific knockout of Selenbp1 and control mice were used for in vivo experiments. Colonic organoids, macrophage co-culture assays, and biochemical assays, including qPCR, immunoblotting, and flow cytometry, were employed to study epithelial proliferation, SUMOylation of Satb2, and macrophage polarization. Clinical samples from patients with Crohn's disease were also analyzed for macrophage markers, as well as Satb2 and SUMO2/3 expression levels. Results Methionine restriction alleviated radiation-induced colonic injury in mice, as evidenced by improved histological scores and reduced inflammatory markers. In contrast, high methionine levels decreased Selenbp1 expression in the colon. Intestinal epithelial-specific Selenbp1 knockout exacerbated radiation-induced colonic mucosal injury, with significantly lower organoid survival rates and budding efficiency post-irradiation. However, this detrimental effect of Selenbp1 knockout was reversed upon methionine restriction, demonstrating the potential of dietary modulation. Furthermore, methionine supplementation led to a reduction in the SUMOylation of Satb2, a key regulator of intestinal epithelial homeostasis. The lower the level of Satb2 SUMOylation, the higher the clinical pathological features of Crohn's disease, such as disease activity. In co-culture assays, methionine supplementation enhanced M1 polarization of macrophages, further indicating a role of methionine in modulating immune responses. In clinical Crohn's disease (CD) specimens, we also found that a higher proportion of M1 macrophages correlated with lower expression levels of Selenbp1. Conclusion Methionine restriction promotes intestinal mucosal repair by regulating Selenbp1 and macrophage polarization, suggesting its potential as a therapeutic strategy for colonic repair.

O-GlcNAcylation of DJ-1 suppresses ferroptosis in renal cell carcinoma by affecting the transsulfuration pathway.

Renal cell carcinoma (RCC) is one of the most common urological malignancies worldwide, and advanced patients often face challenges with chemotherapy resistance and poor prognosis. Ferroptosis, a novel form of cell death, offers potential therapeutic prospects. In this study, we found that DJ-1 was elevated in kidney renal clear cell carcinoma (KIRC), and this abnormal expression pattern was closely associated with clinical pathological characteristics and worse prognosis. Our experiments both in vivo and in vitro revealed that DJ-1 enhanced the malignant characteristics of KIRC, leading to increased tumor growth. Additionally, DJ-1 inhibited ferroptosis through promoting homocysteine (Hcy) synthesis in the transsulfuration pathway in KIRC cells. Mechanistic studies revealed that O-GlcNAc transferase (OGT) mediated O-GlcNAcylation of DJ-1 was crucial for maintaining its homodimeric structure. Importantly, O-GlcNAcylation-deficient mutation of DJ-1 at T19 residue enhanced the interaction between S-adenosyl homocysteine hydrolase (SAHH) and the negative regulatory factor S-adenosyl homocysteine hydrolase-like-1 (AHCYL1), thereby inhibited the activities of SAHH and transsulfuration pathway. In summary, the oncogenic role of DJ-1 in KIRC was closely related to the reduction of ferroptosis, and the O-GlcNAcylation of DJ-1 exerted an antioxidant effect by activating the transsulfuration pathway. Therefore, DJ-1, specifically O-GlcNAcylation of DJ-1 could represent an important target for ferroptosis-based anti-tumor therapy.

PCDH17 induces colorectal cancer metastasis by destroying the vascular endothelial barrier

Compromised vascular integrity facilitates the cancer cells extravasation and metastasis. However, the mechanisms leading to a disruption in vascular integrity in colorectal cancer (CRC) remain unclear. In this study, PCDH17 expression was higher in the vascular endothelial cells of colon cancer with distant metastasis, and the rates of PCDH17+ endothelial cells (ECs) was associated with the M stage in clinical pathological characteristics analysis and correlated with a poor survival prognosis. The liver and lung metastatic dissemination of MC-38 was significantly decreased in PCDH17–/–mice. The ubiquitination and degradation of VEGFR2 was prevented by the interaction between PCDH17 and the E3 ubiquitin ligase MARCH5, which causing the separation of internalized VE-cadherin, and increased the vascular permeability and metastasis of CRC. These results highlight the importance of PCDH17 in maintaining vascular integrity, which has emphasis for endothelial barrier function in metastatic cancer. PCDH17 has the potential to be a marker for predicting tumor metastasis as well as a viable treatment target for CRC.

Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation

BackgroundLow-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood.MethodsThis study comprehensively analyzed several mainstream bioinformatics databases to explore the expression, diagnostic efficacy, clinical pathological features, immune infiltration, prognostic value, and biological functions of NCOA4 in LGG. Immunohistochemistry experiments were conducted using LGG tissue samples collected from our hospital to validate the bioinformatics analysis results.ResultsNCOA4 expression was significantly elevated in LGG (p < 0.05), with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.973, suggesting it as a potential diagnostic marker. High NCOA4 expression was associated with younger age (21–40 years), lower malignancy (oligodendroglioma), and better prognosis (IDHmut-non-codel and IDHmut-codel subtypes) (all p < 0.05) in LGG. Kaplan-Meier survival curves from three databases showed that high NCOA4-expressing LGG patients had better prognosis (all p < 0.05). NCOA4 correlated weakly with B cells, CD8 + T cells, macrophages, and dendritic cells infiltration (all with correlation coefficients r < 0.3, and p < 0.05) in LGG. Multivariate Cox regression identified NCOA4, age, CD8 T cells, and macrophages as LGG independent prognostic factors (all p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that NCOA4’s primary function in LGG is related to autophagy processes (all p < 0.05).ConclusionOur findings suggest that NCOA4 could be a potential prognostic marker and therapeutic target in LGG.

Atypical and worrisome histological features in pleomorphic adenoma: challenging and potentially significant diagnostic pitfall.

Pleomorphic adenoma (PA), the most prevalent salivary gland tumor, exhibits a diverse histological spectrum characterized by epithelial, myoepithelial, and mesenchymal patterns, and secretory products. However, a subset of PAs presents microscopic features suggestive of malignancy, leading to challenging and potentially significant diagnostic pitfalls. A comprehensive retrospective analysis was conducted on the Salivary Gland Tumor Registry, compiled by the authors. A total of 104 cases diagnosed between 1960 and 2023 were retrieved. Clinical findings, pathological features, and molecular genetic results were analyzed. In the study of 104 PA cases, 23 (22.1%) presented features suggestive of pseudoinvasion, with satellite nodules being the most common (43.5%) along with capsular penetration, irregular growth, pseudopodia, lipomatous changes, and vascular permeation. Features of pseudomalignant cytomorphology were found in 97 cases (93.3%), characterized by increased cellularity, cellular atypia, heightened proliferative activity, oncocytic metaplasia, and necrosis. Additionally, 30 cases (28.8%) displayed features resembling other defined malignant salivary gland tumors, particularly myoepithelial carcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma. Despite PA's generally straightforward diagnosis, cases with these features may be mistakenly interpreted as malignant tumors. The shared morphocytological features underscore the complexity of anaccurate diagnosis, emphasizing the need for meticulous examination and a comprehensive assessment, incorporating morphological, molecular, and immunohistochemical analyses to differentiate between benign and malignant salivary gland tumors, in selected cases.

Nomogram for predicting proliferative lupus nephritis in patients with low-level proteinuria.

Proliferative lupus nephritis (LN) is not uncommon in individuals with proteinuria < 0.5 g/24h, highlighting the importance of predicting proliferative nephritis for effective clinical management. We aimed to develop a predictive model for proliferative nephritis in this population. The enrolled 671 biopsy-proven LN patients were divided into low-level proteinuria (< 0.5 g/24 h) and high-level proteinuria (≥ 0.5 g/24 h) groups. The clinical features, pathological characteristics and long-term outcomes of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to construct a predictive nomogram for proliferative nephritis in low-level proteinuria patients and internal validation was performed using bootstrap-resampling. 103 of 671 (15.4%) LN patients had low-level proteinuria, while 43 (41.7%) of whom showed proliferative LN, and the activity index and chronicity index were 5 (IQR [4,7]) and 3 (IQR [2,4]), respectively. The long-term adverse renal events-free survival was preferable in the low-level proteinuria group. The LASSO-logistic regression identified that age, sex, mean arterial pressure, haemoglobin, platelet, 24-h proteinuria and anti-double strands DNA antibodies positivity were associated with proliferative nephritis in those with low-level proteinuria. The predictive model showed an area under curve of 0.900 (95% CI: 0.840-0.960) and a bootstrapped result of 0.894 (95% CI: 0.832-0.965), with good calibration. 41.7% of the patients with low-level proteinuria exhibited proliferative LN when biopsied. The nomogram including clinical, urinary, and laboratory parameters might help with the prediction of proliferative LN before biopsy among patients with low-level proteinuria.

Claudin 18.2: An attractive marker in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive tumor with limited treatment options. Zolbetuximab, a monoclonal antibody against the tight junction protein Claudin 18.2 has recently been developed. At present, few and conflicting data have been reported regarding the clinical-pathological features of Claudin 18.2 expression in PDA. The present study investigated the expression of Claudin 18.2 in histological samples from PDA patients with the aim of verifying its utility as a therapeutic biomarker. Claudin 18.2 immunoreactivity was assessed by immunohistochemical staining on 70 formalin-fixed, paraffin-embedded PDA specimens (28 surgical specimens and 42 fine needle aspiration biopsies). The results obtained were associated with the clinicopathological characteristics and the survival rate of patients. Claudin 18.2 was detected only in neoplastic cells, not in normal pancreatic tissue. Claudin 18.2 was positive in 50% of samples and a higher expression was associated with well- and moderately-differentiated tumors and lymph node-negative status. The high expression of Claudin 18.2 in neoplastic tissue and absence in normal cells suggested that this protein had an attractive role in PDA as both a diagnostic and a prognostic-therapeutic marker. High expression of Claudin 18.2 in neoplastic tissue was associated with more favorable prognostic parameters and the high percentage of positive samples obtained suggests that Zolbetuximab may be suitable for a large number of patients.

Overexpression of MAGE-A2 is Related to the Malignant Degree and Progression of Disease in Patients With Clear Cell Renal Cell Carcinoma.

Melanoma antigen gene-A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in a variety of malignancies. However, the expression of MAGE-A2 for clinical values in the pathophysiology of renal cell carcinoma (RCC) is unknown. For the first time, the present study was conducted to examine the expression and prognostic significance of MAGE-A2 expression in clear cell RCC (ccRCC). MAGE-A2 expression was assayed in 162 well-defined ccRCC samples using immunohistochemistry staining on tissue microarrays. The association between MAGE-A2 expression and clinic-pathologic features as well as survival outcomes were then performed. A significant and positive correlation was found between cytoplasmic expression of MAGE-A2 with tumor size (P=0.008), nucleolar grade (P =0.001), tumor stage (P =0.001), microvascular invasion (P=0.001), invasion to renal pelvis (P=0.032), renal sinus fat (P=0.004), and Gerota's fascia (P=0.028) as well as histologic tumor necrosis (P<0.0001). Increased expression of MAGE-A2 was observed to be associated with shorter progression-free survival (PFS) compared with patients with low expression of MAGE-A2 (P=0.032). Multivariate analysis revealed that tumor size and nucleolar grade are independent predictors of the PFS (P=0.054, P=0.032, respectively). Our results indicated that increased cytoplasmic expression of MAGE-A2 is associated with the malignant degree and progression of ccRCC. This data improved the significance of MAGE-A2 expression and will potentially allow using MAGE-A2 for the prognosis of the disease and immunotherapy in patients with ccRCC.

Clinical features, pathological characteristics, and prognosis of patients with IgA nephropathy complicated with nephrotic syndrome

Nephrotic syndrome (NS) occurs in 5-15% of patients with IgA nephropathy (IgAN), resulting in poorer long-term outcomes compared to those without NS. Clinical features and renal prognosis for patients with both NS and IgAN across different kidney pathologies have not been fully elucidated. This study included patients with primary IgAN through renal biopsy at the First Affiliated Hospital of Sun Yat-sen University from January 2001 to November 2021 presenting with NS. Renal endpoint was defined as a 50% decrease in estimated glomerular filtration rate or progression to end-stage renal disease. A total of 207 patients with IgAN and NS were categorized into four pathological groups: IgAN with mesangial proliferative glomerulonephritis (IgAN-MsPGN) (n = 150), IgAN with minimal change disease (IgAN-MCD) (n = 49), IgAN with membranous nephropathy (IgAN-MN) (n = 7), and IgAN with membranoproliferative glomerulonephritis (IgAN-MPGN) (n = 1). Compared to the IgAN-MsPGN group, the IgAN-MCD group consisted of more males, had a younger average age, lower blood pressure, a lower prevalence of hematuria, and lower serum albumin and creatinine levels, whereas the IgAN-MN group was characterized by an older average age and lower serum creatinine levels. The IgAN-MCD group exhibited the mildest pathological changes among the groups. Of all patients, 133 were followed for an average follow-up period of 52.07 ± 44.04 months. Thirty-seven patients (27.8%) reached the renal endpoint. The IgAN-MCD group showed a higher rate of proteinuria remission and a better renal prognosis than the IgAN-MsPGN group. In conclusions, significant differences in clinicopathological features and long-term prognosis were observed among NS-IgAN patients with varying pathological phenotypes.

Prognostic and diagnostic value of circRNA expression in cervical cancer: a meta analysis.

Cervical cancer (CC) is a highly prevalent malignancy of the reproductive system. This study aimed to methodically assess the function of circular RNAs (circRNAs) as possible indicators of CC, with a specific emphasis on their usefulness in the identification, prediction, and correlation with clinicopathological elements. A comprehensive literature search was conducted using databases such as PubMed, Cochrane Library, Web of Science, Embase, and the China National Knowledge Infrastructure (CNKI). The latest data were extracted on May 3rd, 2024. The diagnostic potential of circRNA expression was evaluated using a range of metrics including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The importance of circRNAs was further evaluated in terms of clinical relevance, pathological features, and prognostic value using pooled odds ratios (ORs) and hazard ratios (HRs). The meta-analysis included 27 studies, which were categorised based on diagnostic applications (n=3), clinicopathological correlations (n=15), and prognostic evaluations (n=23). Elevated expression levels of oncogenic circRNAs were significantly associated with poor clinical indicators, including tumour size (odds ratio [OR] = 0.425, 95% confidence interval [CI]: 0.267-0.676), International Federation of Gynaecology and Obstetrics (FIGO) stage (OR = 0.315, 95% CI: 0.224-0.443), and lymph node metastasis (OR = 2.975, 95% CI: 1.816-4.872). This upregulation of oncogenic circRNA was also identified as a predictor of worse survival outcomes, with a hazard ratio (HR) of 2.13 (95% CI: 1.73-2.62, P < 0.001). The downregulation of circRNAs with tumour-suppressor properties was similarly associated with poor clinical parameters, such as tumour size (OR = 0.310, 95% CI: 0.102-0.941), FIGO stage (OR = 0.231, 95% CI: 0.101-0.527), and lymph node metastasis (OR = 2.430, 95% CI: 1.156-5.110), and was indicative of a worsened prognosis (HR = 2.20, 95% CI: 1.03-4.70, P = 0.042). In terms of diagnostic value, the pooled sensitivity, specificity, and area under the curve (AUC) were calculated to be 0.85, 0.83, and 0.91, respectively. The results of our meta-analysis indicate that circRNAs have the potential to serve as promising biomarkers for CC diagnosis, prognosis, and clinicopathology. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024544997.

Golgi protein 73: charting new territories in diagnosing significant fibrosis in MASLD: a prospective cross-sectional study.

To explore the correlation between serum Golgi protein 73 (GP73) levels and the degree of fibrosis in Metabolic dysfunction associated steatotic liver disease (MASLD); to establish a non-invasive diagnostic algorithm based on serum GP73 and liver elasticity. This is a prospective cross-sectional study, including 228 patients diagnosed with MASLD from May 2018 to January 2024 at two tertiary hospitals. Clinical data and hepatic pathological features and the correlation between serum GP73 and liver fibrosis were assessed. A new algorithm was conducted after logistic regression. Receiver Operating Characteristic (ROC) curve was used to compare its diagnostic performance with traditional models. Significant fibrosis was diagnosed in 37.2% (85/228) patients. Serum GP73 levels were markedly higher in patients with significant fibrosis than in those without (128 ng/mL v.s 46 ng/mL, p< 0.001). Serum GP73 levels independently predicted significant liver fibrosis (adjusted odds ratio, aOR 1.028, p< 0.001). A new algorithm based on GP73 was developed with a higher area under ROC (AUC) of 0.840 than that of Fibrosis index-4 (p< 0.001). Serum GP73 is an independent risk factor for significant liver fibrosis in MASLD, and the GFA (GP73-Fibroscan-Age) model has good diagnostic efficacy for significant liver fibrosis.

Axillary Overtreatment in Patients with Breast Cancer After Neoadjuvant Chemotherapy in the Current Era of Targeted Axillary Dissection.

In the current era of targeted axillary dissection (TAD), there are still cases where axillary lymph node dissection (ALND) is indicated, but histopathological examination confirms the regression of nodal metastases (ypN0). In this situation, ALND may represent undesirable overtreatment. A retrospective study at the Comprehensive Cancer Centre was conducted based on a prospectively maintained database. Patients who underwent surgery after neoadjuvant chemotherapy (NAC) between 2020 and 2023 were selected, specifically those for whom ALND was directly indicated after NAC. Subsequently, clinical-pathological characteristics were compared between cases with ypN0 and those with persistent metastases (ypN+). The reasons for indicating ALND in ypN0 cases were extracted from the medical records. ALND was indicated in 118 cases across 117 patients, of which ypN0 was observed in 44 cases (37%). There were significantly more ypN0 cases for inflammatory carcinomas (68%), the non-luminal HER2-positive phenotype (76%), and carcinomas with histopathological regression of the primary tumor (76%) or the persistence of only the non-invasive component of ypTis (67%). Typical reasons for ALND in ypN0 cases included inflammatory carcinoma (n = 13, 29.5%), locally advanced carcinoma (n = 5, 11.4%), occult carcinoma (n = 2, 4.5%), or persistent lymphadenopathy on ultrasound examination after NAC, especially in the tumor phenotypes HER2-positive and triple-negative breast cancer (TNBC) (n = 8, 18.2%). Through real-world evidence data analysis, subgroups of breast cancer patients treated with NAC were identified who may experience surgical overtreatment in the axilla. These include patients with inflammatory carcinoma, locally advanced carcinoma, occult carcinoma, or patients with persistent lymphadenopathy on US examination after NAC, particularly in the tumor phenotypes HER2-positive and TNBC.

Clinical effects of surgical resection of osteosarcoma in proximal fibula and long-term follow-up of health status

Purpose: This study aimed to evaluate the health status and quality of life in patients with osteosarcoma of the proximal fibula following surgical treatment. The procedure necessarily involved resection of the peroneal nerve, resulting in iatrogenic footdrop. Methods: From January 2005 to 26 August 2020 patients with osteosarcoma in the proximal fibula were treated at the oncology department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital. Clinical-pathological features as well as outcomes of these patients were investigated. Meanwhile, to clarify their health status, the SF-36 health survey questionnaire was administered at 12, 24, and 36 months post-diagnosis. Results: The outcomes for patients with osteosarcoma in the proximal fibula were encouraging. Both the three-year disease-free survival rate and the overall survival rate were recorded at 88.5% (23/26). Data from the SF-36 health survey questionnaire, completed by 20 patients who underwent limb-sparing surgery, revealed that at 24 months, patients perceived themselves as less healthy, both physically and emotionally, compared to their status at 12 months. Despite observing significant recovery at 36 months, the health status did not return to the levels reported at 12 months. The majority of patients (n = 17) identified “footdrop after surgery” as the primary factor affecting their quality of life. Conclusions: Osteosarcomas affecting the proximal fibula typically demonstrate a favorable prognosis following multi-modal treatment. However, patients’ health status, including psychological well-being, requires improvement. Oncologists should strive to achieve an “equilibrium point” that minimizes the risk of recurrence while preserving peroneal nerve function.

MicroRNAs Expression Profile in MN1-Altered Astroblastoma.

Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (MN1) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma. A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on MN1-altered astroblastomas (n = 8) and normal brain controls (n = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs. Eight MN-altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated. MN1-altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.

The Role of 3D Virtual Anatomy and Scanning Environmental Electron Microscopy in Understanding Morphology and Pathology of Ancient Bodies.

Mummy studies allow to reconstruct the characteristic of a population in a specific spatiotemporal context, in terms of living conditions, pathologies and death. Radiology represents an efficient diagnostic technique able to establish the preservation state of mummified organs and to estimate the patient's pathological conditions. However, the radiological approach shows some limitations. Although bone structures are easy to differentiate, soft tissue components are much more challenging, especially when they overlap. For this reason, computed tomography, a well-established approach that achieves optimal image contrast and three-dimensional reconstruction, has been introduced. This original article focuses attention on the role of virtual dissection as a promising technology for exploring human mummy anatomy and considers the potential of environmental scanning electron microscopy and X-ray spectroscopy as complementary approaches useful to understand the state of preservation of mummified remains. Ancient mummy corps have been analyzed through Anatomage Table 10 and environmental scanning electron microscope equipped with X-ray spectrometer; Results: Anatomage Table 10 through various volumetric renderings allows us to describe spine alteration due to osteoarthritis, dental state, and other clinical-pathological characteristics of different mummies. Environmental scanning electron microscope, with the advantage of observing mummified samples without prior specimen preparation, details on the state of tissue fragments. Skin, tendon and muscle show a preserved morphology and keratinocytes, collagen fibers and tendon structures are easily recognizable. Furthermore, X-ray spectrometer reveals in our tissue remains, the presence of compounds related to soil contamination. This investigation identifies a plethora of organic and inorganic substances where the mummies were found, providing crucial information about the mummification environment. These morphological and analytical techniques make it possible to study mummified bodies and describe their anatomical details in real size, in a non-invasive and innovative way, demonstrating that these interdisciplinary approaches could have great potential for improving knowledge in the study of ancient corpses.

Apolipoprotein B/Apolipoprotein A1 ratio is an independent prognostic factor in pancreatic cancer.

The relationship between serum lipids and prognosis of pancreatic cancer has not been confirmed. Our purpose in the study was to investigate the associations between serum lipids level and prognosis in patients with pancreatic cancer. A retrospective study was performed on 286 pancreatic cancer patients who admitted to our hospital from January 1, 2017 to December 31, 2021. Serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, progression free survival (PFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model. Regarding serum lipids level, compared to normal apolipoprotein B/ apolipoprotein A (ApoB/ApoA1), high ApoB/ApoA1 level indicated a shorter OS (HR:2.028, 95% CI: 1.174-2.504, P = 0.011) and a shorter PFS (HR:1.800, 95% CI: 1.076-3.009, P = 0.025). Other serum lipid molecules were not associated with PFS and OS. ApoB/ApoA1 might be an independent prognostic factor of pancreatic cancer.

Surveillance Breast MRI in Women with a History of Breast Cancer: Association with Occurrence of Advanced Second Breast Cancer.

Background Studies on the association between surveillance breast MRI in women with a personal history of breast cancer (PHBC) and advanced second breast cancer are lacking. Purpose To investigate the association between postoperative surveillance breast MRI and advanced second breast cancer in women with a PHBC by using propensity score matching (PSM). Materials and Methods Women who underwent breast cancer surgery between January 2009 and December 2014 were retrospectively identified at a single tertiary center. Second breast cancer was defined as ipsilateral or contralateral breast cancer diagnosed at least 1 year after surgery, and advanced second breast cancer was defined as second breast cancer (a) grade T2 or higher or lymph node-positive or (b) T1c triple-negative or human epidermal growth factor receptor 2-positive. Women who underwent surveillance MRI and those who did not were matched using propensity scores according to 13 clinical-pathologic characteristics. Outcomes were compared using logistic regression analysis. Results Among the 3688 women (mean age, 51.1 years ± 10.5 [SD]), 2130 underwent surveillance MRI (MRI group) and 1558 did not (non-MRI group); 1062 patient pairs were matched. Advanced second breast cancer proportions for non-MRI and MRI groups were 1.7% (27 of 1558 participants) and 0.4% (eight of 2130 participants) before PSM and 1.6% (17 of 1062 participants) and 0.7% (seven of 1062) after PSM. Surveillance MRI was associated with lower odds of advanced second breast cancer before PSM (odds ratio [OR], 0.21 [95% CI: 0.10, 0.47]; P < .001) and after PSM (OR, 0.41 [95% CI: 0.17, 0.99]; P = .048). The proportion of symptomatic second breast cancers was higher in the non-MRI group before PSM (25% [16 of 65 second cancers] vs 6.4% [three of 47]; P = .01) and after PSM (21% [10 of 48] vs 3.2% [one of 31]; P = .003). Conclusion In women with a PHBC, MRI surveillance was associated with lower odds of advanced second breast cancer before and after PSM. © RSNA, 2025 Supplemental material is available for this article.