Clinicopathological Features Research Articles

Targeting RAF1 gene fusions with MEK inhibition in metastatic melanoma

Abstract The biological and clinical relevance of gene fusions in melanoma is unknown. Reports and preclinical data have suggested that tumor cells with specific rearrangements such as RAF1 gene fusions could be therapeutically targeted. To investigate the relevance of targeted therapy in patients with melanoma harboring RAF1 gene fusions, we reviewed records of 1268 melanoma patients with targeted sequencing data at the Dana-Farber Cancer Institute. We identified 9 cases and report here on their clinicopathologic characteristics. We describe the favorable outcome of 2 patients who received MEK inhibitor therapy, including 1 patient with a durable response. We coalesced our data with published reports of patients with RAF1 gene fusions who were treated with targeted therapy. We find that single-agent MEK inhibition has anti-tumor activity in melanoma patients harboring an RAF1 gene fusion, and we propose that patients with RAF1 gene fusions should be considered for single-agent MEK inhibitor therapy.

Identification of sentinel lymph node macrometastasis in breast cancer by deep learning based on clinicopathological characteristics

The axillary lymph node status remains an important prognostic factor in breast cancer, and nodal staging using sentinel lymph node biopsy (SLNB) is routine. Randomized clinical trials provide evidence supporting de-escalation of axillary surgery and omission of SLNB in patients at low risk. However, identifying sentinel lymph node macrometastases (macro-SLNMs) is crucial for planning treatment tailored to the individual patient. This study is the first to explore the capacity of deep learning (DL) models to identify macro-SLNMs based on preoperative clinicopathological characteristics. We trained and validated five multivariable models using a population-based cohort of 18,185 patients. DL models outperform logistic regression, with Transformer showing the strongest results, under the constraint that the sensitivity is no less than 90%, reflecting the sensitivity of SLNB. This highlights the feasibility of noninvasive macro-SLNM prediction using DL. Feature importance analysis revealed that patients with similar characteristics exhibited different nodal status predictions, indicating the need for additional predictors for further improvement.

The impact of age on clinicopathological features and treatment results in patients with localised prostate cancer receiving definitive radiotherapy.

This study assessed the biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), overall survival (OS), and side effects in patients aged < 70 and ≥ 70 years following definitive radiotherapy (RT). It also analysed the correlation between age at diagnosis and clinicopathological characteristics of prostate cancer (PCa). The prognostic factors for bDFS, PCSS, and OS were determined through univariable and multivariable analyses. Two age groups were also compared in terms of acute and late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities, the predictors of which were determined through logistic regression analysis. Of the 1,328 patients, 715 (53.8%) and 613 (46.2%) were aged < 70 and ≥ 70 years, respectively. Median follow-up time was 84.5 months. No significant differences in the 7-year bDFS (86.3% vs. 86.8%) and PCSS rates (92.9% vs. 93.3%) were found between the ≥ 70 and < 70 age groups. The multivariable analysis showed that advanced clinical T stage, high International Society of Urological Pathology (ISUP) grade, and high-risk disease independently predicted poor bDFS and PCSS. Metastatic lymph nodes were another bDFS prognostic factor. The multivariable analysis identified age ≥ 70 years, cardiac events at diagnosis, advanced stage, higher ISUP grade, and non-use of simultaneous integrated boost technique as negative factors for OS. Additionally, diabetes and transurethral resection of the prostate (TUR-P) independently predict late-grade ≥ 2 GU toxicity. Definitive RT is a safe and effective treatment for patients with localised PCa no matter their age. Although patients over 70 years have higher risk factors and comorbidities, their bDFS, PCSS, and toxicities were comparable to those of patients aged < 70 years.

TBL2 Promotes Tumorigenesis via PRMT5/WDR77-Mediated AKT Activation in Breast Cancer.

Breast cancer (BC) is a common malignancy that affects women worldwide. Although transducing beta-like 2 (TBL2), a member of the WD40 repeat protein family, has been implicated in various intracellular signaling pathways, its precise function in BC remains unclear. The expression of TBL2 is analyzed using real-time PCR, western blotting, and immunohistochemistry in BC patient specimens. Kaplan-Meier survival analysis is employed to assess its prognostic significance. Proteomic analysis, immunoprecipitation tests, and protein immunoblotting are employed to examine the impact of TBL2 on AKT phosphorylation activation. The findings reveal selective overexpression of TBL2 in BC, correlating significantly with various clinicopathological characteristics and poor survival outcomes in patients with BC. Through in vivo and in vitro experiments, it is observed that TBL2 suppression inhibits BC cell proliferation, while TBL2 overexpression has the opposite effect. Mechanistically, TBL2 is identified as a scaffolding protein that promotes PRMT5 and WDR77 interaction. This interaction enhances the methyltransferase activity of PRMT5, leading to increased AKT phosphorylation activation and promotion of breast cancer cell proliferation. In conclusion, this study uncovers a novel function of TBL2 in the activation of AKT by PRMT5 and suggests TBL2 as a potential therapeutic target for BC treatment.

Unravelling switch/sucrose non-fermentable (SWI-SNF) complex-deficient thoracic tumours: a clinicopathological comparative on undifferentiated tumours and non-small cell lung carcinomas with BRG1 and BRM deficiency

AimsThis study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cell lung carcinomas (SWI/SNF-dNSCLC) and to address cases with...

Paediatric oral and maxillofacial biopsies: A retrospective institutional archival study.

This is a retrospective cross-sectional study of oral and maxillofacial biopsies in paediatric population, up to 16 years of age from 1991 to 2021. This study aimed to investigate the frequency, demographic and clinicopathological characteristics of paediatric biopsies according to the diagnosis categories of the main tertiary centre in Malaysia. A total of 17294 histopathological reports from Diagnostic Oral Pathology Unit between 1991 and 2021 were retrieved. One thousand eleven histopathological reports that fulfilled the inclusion and exclusion criteria were included. Information of interest was extracted from histopathological reports. The lesions were categorised into 10 diagnosis categories. Descriptive and correlation analysis were performed. Paediatric oral and maxillofacial biopsies accounted for 5.9% of the total biopsies received. The peak incidence of diagnosis was in age range of 12 to 16 years old and mean age of 11.6 years old (±3.5), with female preponderance. The most common category of diagnosis was salivary gland pathology with mucocele (30%) being the most frequently diagnosed lesions. Lip and labial mucosa were the commonest site of occurrence. Specimen sizes smaller than 1 cm were the most common specimen diameter with mean size of 1.6 cm (±1.5). Age, site of occurrence and specimen size were statistically significant (P < 0.05) with paediatric oral and maxillofacial biopsies. This is a large-scale study of paediatric oral and maxillofacial biopsies of a tertiary centre over three decades. We hope this data is useful for chairside assessment and aids in diagnosis making.

Identification of novel markers for neuroblastoma immunoclustering using machine learning

BackgroundDue to the unique heterogeneity of neuroblastoma, its treatment and prognosis are closely related to the biological behavior of the tumor. However, the effect of the tumor immune microenvironment on neuroblastoma needs to be investigated, and there is a lack of biomarkers to reflect the condition of the tumor immune microenvironment.MethodsThe GEO Database was used to download transcriptome data (both training dataset and test dataset) on neuroblastoma. Immunity scores were calculated for each sample using ssGSEA, and hierarchical clustering was used to categorize the samples into high and low immunity groups. Subsequently, the differences in clinicopathological characteristics and treatment between the different groups were examined. Three machine learning algorithms (LASSO, SVM-RFE, and Random Forest) were used to screen biomarkers and synthesize their function in neuroblastoma.ResultsIn the training set, there were 362 samples in the immunity_L group and 136 samples in the immunity_H group, with differences in age, MYCN status, etc. Additionally, the tumor microenvironment can also affect the therapeutic response of neuroblastoma. Six characteristic genes (BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM) were identified by machine learning, and these genes are associated with multiple immune-related pathways and immune cells in neuroblastoma.ConclusionsBATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM may serve as biomarkers that reflect the conditions of the immune microenvironment of neuroblastoma and hold promise in guiding neuroblastoma treatment.

Intestinal subtype as a biomarker of response to neoadjuvant immunochemotherapy in locally advanced gastric adenocarcinoma: insights from a prospective phase II trial.

Neoadjuvant immunochemotherapy (NAIC) markedly induces pathologic regression in locally advanced gastric adenocarcinoma (GAC). However, specific biomarkers are still lacking to effectively identify the beneficiary patients for NAIC. A prospective, single-arm, phase II study was conducted to treat locally advanced GAC with NAIC (NCT05515796). Correlation between clinicopathological characteristics and neoadjuvant efficacy was investigated. Bulk RNA-seq data from 104 samples (from 75 patients in two independent cohorts) and scRNA-seq data from 105 treatment-naïve GACs were comprehensively analyzed to decipher the association of epithelial and microenvironmental characteristics and clinical responses. The pre-specified primary endpoints were achieved: pathological complete regression (pathCR) rate was 30%, major pathological regression (MPR) rate was 43%, while the regimen was well tolerated. Analysis of baseline clinical-pathological parameters revealed the intestinal subtype of Lauren's classification as a key feature stratifying patients with increased sensitivity to NAIC. Mechanistically, an increased pool of DNA damage repair (DDR)-active cancer cells and enrichment of CLEC9A+ dendritic cells (DCs) in the tumor microenvironment were associated with enhanced responsiveness of the intestinal subtype GAC to NAIC. More importantly, an intestinal-subtype specific signature model was constructed by the machine learning algorithm NaiveBayes via integrating the transcriptomic features of both DDR-active cancer cells and CLEC9A+ DCs, which accurately predicted the efficacy of NAIC in multiple independent GAC cohorts. Intestinal subtype is a histological biomarker of enhanced sensitivity of GAC to NAIC. The Intestinal-subtype specific signature model is applicable to guide NAIC for patients with locally advanced GAC.

Bladder cancer: a retrospective audit at a single radiation oncology unit of an academic hospital in Johannesburg, South Africa

BackgroundBladder cancer (BCa) is one of the most common urological cancers and remains a leading cause of cancer-related mortality worldwide. Bladder cancer is associated with a range of risk factors, with smoking being one of the most significant contributors. In addition to smoking, exposure to certain chemicals, particularly aromatic amines found in industries such as dye, rubber, leather, and textiles, also increases the risk of bladder cancer. In low-and-middle countries with lower Human Development Index (HDI), data on the underlying causes, incident rate, modes of presentation, treatment, and prognosis of bladder cancer remains unclear and often appear to be inadequate. This study aimed to assess the prevalence, mode of presentation, treatment, and risk factors associated with bladder cancer in Johannesburg, South Africa. By examining these factors, the study seeks to identify possible patterns or predisposing factors that contribute to the development and progression of bladder cancer, which could generate insights that could help to reduce the significant morbidity and mortality associated with this cancer.MethodsThis retrospective study analyzed secondary data from 115 patients who were treated in the radiation oncology unit of an academic hospital between January 2010 and December 2020. By reviewing the medical records of these patients, the study aimed to gather comprehensive information on the prevalence of bladder cancer, modes of presentation, treatment approaches, and associated risk factors. Bladder cancer in this study was assessed using a comprehensive analysis of patient data on demographics, risk factors, clinicopathological aspects, and the specific therapies received. A comparison of patients with squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder was conducted as part of this study. This comparison aimed to explore differences in demographic profiles, risk factors, clinicopathological characteristics, and treatment outcomes between these two histological subtypes.ResultsA total of 115 patients presenting with bladder cancer symptoms were referred to the academic hospital for evaluation and treatment. The incidence rate of bladder cancer was highest among patients with a mean age of 60.7 ± 14.9. Males constituted 60.9% of the cases, resulting in a male-to-female ratio of 1.6:1. The most common risk factors associated with bladder cancer complications included smoking, being male, black ethnicity and increasing age. Transitional cell carcinoma remained the most prevalent histological subtype at the academic hospital, compared to squamous cell carcinoma (SCC). Patients with transitional cell carcinoma (TCC) were more likely to be older (odds ratio (OR): 1.03, 95% Confidence Interval (CI): 1.01–1.06, p = 0.029), male (OR: 2.60, 95% CI:1.10–6.04, p = 0.030). The study also found that most of the TCC cases were among black patients, though white patients were four times more likely to present with TCC compared to SCC (OR:4.22, 95% CI: 1.43–12.48, p = 0.009).ConclusionBladder cancer is still widespread in LMICs, with lower HDI, with elderly males being at risk. To aggressively prevent mortality and morbidity from bladder cancer, bladder cancer health awareness must be maintained to improving prevention, as well as early detection, management and comprehensive patient care and health services for bladder cancer patients. These findings highlight the importance of targeted screening and prevention strategies for high-risk groups, particularly older males with a history of smoking.

Histopathological assessment of AIDS-defining malignancies in the gastrointestinal tract presenting with acute abdomen: Improving diagnostic timeliness and patient care.

While a large number of cases in an HIV setting may be attributed to infections, there has also been a rise in HIV- associated malignancies such as Kaposi sarcoma and aggressive B-cell lymphoma. To describe the clinicopathological features of cases with acute abdomen secondary to AIDS-defining malignancy in the gatrointestinal tract. This is a retrospective analysis of all cases presenting with acute abdomen and histologically diagnosed AIDS-defining malignancies of the gastrointestinal tract over a period of 8 years in our centre. Clinicopathological characteristics were retrieved from the laboratory information system. Archived haematoxylin and eosin-stained sections and immunohistochemical stains were reap- praised. A total of 13 cases, which consisted of 5 males and 8 females, with an average age of 35 years formed the study sample. All the patients were HIV-positive on antiretroviral therapy, and presented with acute abdomen. Intraoperatively, there were five intussusceptions, three strictures, three perforated tumours and two luminal occlusions. Histopathology confirmed five cases of Kaposi sarcoma and eight cases of high-grade B-cell lymphomas. Two patients with high-grade B-cell lymphomas died after surgical intervention. Expedited histopathological assessment of bowel resection in HIV-infected patients could improve clinical outcomes with early treatment.

Blood lipid profiles associated with metastatic sites in advanced gastric cancer

BackgroundThis study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression.MethodsPathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed.ResultsIn GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis.ConclusionSpecific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study.

Nausea and vomiting are major non-hematological adverse events associated with niraparib maintenance therapy. This study aimed to investigate the time-trend patterns of niraparib-induced nausea and vomiting (NINV) and the associated risk factors in patients with ovarian cancer. In this prospective study, we enrolled patients with stage III-IV epithelial ovarian cancer who received niraparib as frontline maintenance therapy. The clinicopathological characteristics and time-trend patterns of patients with NINV were collected through in-person surveys and electronic medical records from the National Cancer Center. Of 53 patients, 50 (94.3%) were diagnosed with high-grade serous ovarian carcinoma. BRCA mutations and homologous recombination deficiency (HRD) were identified in 23 (43.4%) and 32 (60.4%) patients, respectively. Thirty-one patients (58.5%) had NINV. Time-trend analyses revealed that the first peak intensity of NINV was reached at 3 h post-dose, and the second peak intensity was reached at 11 h post-dose. NINV significantly decreased from week 1 to weeks 8 and 12. In multivariate analyses of risk factors for NINV, HRD-positive tumors (p<0.001) and prior experience of chemotherapy-induced nausea and vomiting (p=0.004) were associated with the occurrence of NINV. Pre-emptive treatment with antiemetics are required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confirm these findings and to develop optimal preventive strategies for NINV.

High α-SMA expression in the tumor stroma is associated with adverse clinical parameters in mismatch repair-proficient colorectal cancers only.

As mismatch repair status confers differential prognosis in colorectal cancers, this study aimed to determine associations of α-smooth muscle actin (α-SMA) protein expression in mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) colorectal tumors with clinicopathologic and prognostic features. Tissue microarrays from patients with colorectal cancer, immunostained with α-SMA, were assessed through digital image analysis. Total (n=962), pMMR (n=782), and dMMR (n=156) stromal H-scores were assessed for associations with clinicopathologic and survival data. Higher α-SMA expression was correlated with pMMR status (P=5.2223×10-8). In the pMMR subgroup, higher α-SMA stromal expression at the tumor periphery was correlated with higher T stage (P=.002), perineural invasion (P=.038), infiltrative tumor edge (P=.01), involved nodal status (P=.036), metastases (P=.013), synchronous metastases (P=.007), recurrence (P=.004), and both 3-year and 5-year survival (P=.018). dMMR tumors showed no significant correlations with α-SMA staining. The findings highlight that immunostaining with α-SMA in pMMR colorectal tumors, especially at the tumor periphery, has the potential to identify patients with adverse prognostic features. Digital assessment of α-SMA may offer improved objectivity, accuracy, economy of time, and risk stratification for management.

Are background breast parenchymal features on preoperative breast MRI associated with disease-free survival in patients with invasive breast cancer?

To evaluate whether breast parenchymal features of the contralateral breast on preoperative MRI are associated with primary breast cancer characteristics and disease-free survival (DFS) in women with invasive breast cancer. Women with newly diagnosed invasive breast cancer who underwent preoperative breast MRI followed by surgery were retrospectively evaluated. Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI and background diffusion signal (BDS) on diffusion-weighted MRI of the contralateral breast were qualitatively assessed using a four-category scale: minimal, mild, moderate, or marked. Primary breast cancer characteristics were compared based on the degree of BPE or BDS. Cox proportional hazards models were used to evaluate the association between MRI parenchymal features and DFS after adjusting for clinicopathologic features. A total of 515 women (mean age, 54years) were included. Of whom, 46 (8.9%) patients who developed disease recurrence at a median follow-up of 60months were observed. A high level (moderate/marked) of BPE or BDS was associated with younger age (≤ 45) and premenopausal status (all P < 0.05) compared to a low level (minimal/mild), but it was not associated with primary cancer characteristics such as tumor stage, grade, or subtype. Multivariable Cox proportional hazards analysis demonstrated that larger tumor size (> 2cm) (hazard ratio [HR], 3.877; P < . 001), triple-negative subtype (HR, 2.440; P = .013), and axillary node metastasis (HR, 1.823; P = .049) were associated with worse DFS. No associations were observed between background parenchymal features and disease outcomes. MRI parenchymal features, including BPE and BDS, of the contralateral breast showed no associations with primary breast cancer characteristics or DFS in women with invasive breast cancer.

Volume of hepatoid component and intratumor M2 macrophages predict prognosis in patients with hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS), a subtype of gastric cancer (GC), includes multiple tumor components, such as enteroblastic and tubular adenocarcinoma components. However, which component mostly contributes to the aggressive behavior of HAS remains unclear. Moreover, the role of tumor-associated macrophages (TAMs) has not been explored in HAS. This study evaluated the clinical significance of the proportion of the hepatoid component within the tumor, CD163 + macrophages, and macrophage colony-stimulating factor-1 (CSF-1) in HAS. In total, 56 cases of primary HAS were analyzed. In each case, hepatoid (HC), enteroblastic (EC), and tubular (TC) components were identified, and the ratio of HC to the entire tumor (hepatoid component ratio, HCR) was assessed to examine the correlation between HCR and clinicopathological features. Immunohistochemical staining for CD163 and CSF-1 was performed, and differences in immunohistochemical results among the three tumor components were analyzed. In each tumor component, the prognostic impact of CD163 and CSF-1 was examined. A high HCR was associated with worse overall survival (OS). CD163 + TAMs and CSF-1 immunoreactivity score in HC were significantly higher than those in the other components. High infiltration of CD163 + TAMs and a high CSF-1 immunoreactivity score in HC were associated with an aggressive course and worse OS. Multivariate analysis revealed the proportion of HC in HAS as an independent prognostic factor (HR = 3.176, p = 0.006). The HCR and CD163 + TAMs may be useful prognostic predictors, and TAMs may be novel therapeutic targets of HAS.

Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.

The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies. The study included 15489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database. A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies. The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

Clinicopathological features of lacrimal gland biopsy lesions in 582 Chinese patients

Background This study was conducted to assess the clinicopathological characteristics of biopsy lesions in the lacrimal gland, in response to evolving pathological technologies and the emergence of new diseases. A retrospective review of case notes was conducted for 582 patients with biopsied lacrimal gland lesions at West China Hospital of Sichuan University in China. This study, spanning from January 1, 2010, to December 31, 2021, recorded demographics, clinical features, imaging findings, histopathological diagnoses, and recurrence rates. In a cohort of 582 patients, the mean age was 47.5 years, with 318 being female. Bilateral disease was present in 127 patients. Common signs and symptoms included a palpable mass, lid swelling, proptosis, and decreased ocular movements or diplopia. The predominant pathologies identified were inflammation, epithelial tumors, and lymphoproliferative lesions. Patients with inflammation (mean 32.8 months) experienced symptoms for a longer period compared to those with lymphoproliferative lesions (mean 22.2 months) (95% confidence interval [CI] 1.53–19.27, P = 0.022). Younger patients tended to have structural lesions (mean 42.5 years) (95%CI 4.74–21.59, P = 0.003), inflammation (mean 42.9 years) (95%CI 0.46–6.57, P<0.001), or epithelial tumors (mean 46.4 years) (95%CI 6.21–12.38, P<0.001), while older patients more frequently had lymphoproliferative lesions (mean 55.7 years). The period from 2016 to 2021 saw a higher diagnosis rate of biopsied lacrimal gland lesions than from 2010 to 2015. During this later period, there was an increase in cases of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and malignant epithelial tumors, while lymphoid hyperplasia cases declined. Adenoid cystic carcinoma showed the highest recurrence rate, with lesion extent and Ki-67 index identified as independent risk factors in our study. Inflammation, epithelial tumors, and lymphoproliferative lesions were the three primary causes of lacrimal gland lesions in our study group. Among the inflammatory conditions, IgG4-ROD was the most specific. The incidence of lacrimal gland lesions has risen, particularly for IgG4-ROD. Adenoid cystic carcinoma among the lacrimal gland lesions was prone to recurrence, with the extent of the lesion and Ki-67 index serving as independent risk factors.

Correlation Between Serum and Tissue SIRT1 Levels in Patients With Esophageal Squamous Cell Carcinoma.

Identifying prognostic and molecular markers as therapeutic targets for esophageal squamous cell carcinoma (ESCC) could enhance the efficacy of multidisciplinary treatments. While tissue expression of sirtuin 1 (SIRT1) has been linked to tumor progression in ESCC, prognostic significance of serum SIRT1 levels and their correlation with tissue SIRT1 remains unexplored. This study aimed to investigate the correlation between serum and tissue SIRT1 levels in patients with ESCC. A total of 38 patients diagnosed with ESCC who were untreated preoperatively were recruited for this study. SIRT1 expression in the surgical specimens was assessed through immunostaining, while serum SIRT1 levels were measured using an enzyme-linked immunosorbent assay. We analyzed the association between tissue and serum SIRT1 levels, clinicopathological features, and patient prognosis. Positive SIRT1 expression in tissue was significantly associated with deeper tumor depth (p=0.020). It was also significantly associated with poorer overall survival (OS) and relapse-free survival (RFS) (p=0.041 and p=0.012, respectively). Elevated serum SIRT1 levels were significantly correlated with increased tumor depth and weight loss (p=0.012 and p=0.030). While higher serum SIRT1 levels tended to be associated with poorer OS (p=0.069), no significant correlation was found between SIRT1 expression in tissue and its concentration in serum. SIRT1 tissue expression may be a valuable prognostic marker in ESCC. However, the clinical significance of serum SIRT1 levels appears to differ from that of its tissue expression. Future research is required to clarify the role of serum SIRT1 in ESCC.

The role of adjuvant endocrine treatment in ER+, PR−, HER2− early breast cancer: a retrospective study of real-world data

Purpose: Estrogen receptor-positive (ER+), progesterone receptor-negative (PR-) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) often developed resistance to endocrine treatment (ET). We aimed to explore (1) the different clinicopathological features between ER+/PR+/HER2- and ER+/PR-/HER2- BC, and (2) whether ER+/PR-/HER2- early BC patients could benefit from adjuvant ET. Methods: All patients treated for ER+/HER2- early BC who underwent surgery between 2010 and 2021 from a BC database in China were retrospectively examined. The cases followed up for less than six months were excluded. Results: The records of ER+/PR+/HER2- (n = 10843) and ER+/PR-/HER2- BC (n = 1193) cases were reviewed, with median follow-up times of 35.8 and 47.0 months, respectively. Compared with ER+/PR+/HER2- cases, ER+/PR-/HER2- BC occurred more in postmenopausal women (73.1% vs. 52.9%, p = 0.000) and were more likely to be T > 2 cm (40.6% vs. 37.6%, p = 0.048) and Ki67 > 20%+ (48.1% vs. 36.9%, p = 0.000). However, ER+/PR-/HER2- cases had fewer nodal involvement (32.9% vs. 36.9%, p = 0.000). Approximately 82.2% (981/1193) of ER+/PR-/HER2- patients received ET, while approximately 17.8% (212/1193) did not. Compared to patients did not receive adjuvant ET, the ET group had similar disease-free survival (DFS) (HR = 1.33, 95% confidence interval (CI): 0.68–2.59, p = 0.444) and overall survival (OS) (HR = 1.17, 95%CI: 0.37–3.68, p = 0.799). 65.7% of recurrent ER+/PR-/HER2- patients experienced distant relapse (65.7% vs. 48.2% (for ER+/PR + cases), p = 0.011). By comparison, recurrent ER+/PR+/HER2- patients were more likely to experience only local relapse (31.6% vs. 14.9% (for ER+/PR- cases), p = 0.007). Conclusions: ER+/PR-/HER2- BC was a special subtype with aggressive clinicopathological features and more tend to have distant metastasis rather than nodal involvement or local relapse. ER+/PR-/HER2- early BC did not seem to benefit from adjuvant ET.

ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33

Suppression of Tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor/ Toll-like receptor superfamily, and its specific ligand is Interleukin-33 (IL-33). IL-33/ ST2 signaling has been implicated in numerous inflammatory and allergic diseases, as well as in promoting malignant behavior of tumor cells and angiogenesis. However, the precise role of ST2 in gastric cancer angiogenesis remains incompletely elucidated. We observed a significant correlation between high expression of ST2 in gastric cancer tissues and poor prognosis, along with various clinicopathological features. In vitro experiments demonstrated that the IL-33/ ST2 axis activates the PI3K/AKT/NF-κB signaling pathway through TRAF6, thereby promoting VEGFA-mediated tumor angiogenesis; meanwhile sST2 acts as a decoy receptor to regulate the IL-33/ST2L axis. Consistent findings were also observed in subcutaneous xenograft tumor models in nude mice. Furthermore, we investigated the molecular mechanism by which IL-33 promotes ST2L expression in GC cells via upregulation of transcription factors YY1 and GATA2 through intracellular signaling pathways.