Role of clinicopathological variables in predicting recurrence and survival outcomes after surgery for non-metastatic renal cell carcinoma: Systematic review and meta-analysis.

Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.

Molecular and clinicopathological features of KIT/PDGFRA wild-type gastrointestinal stromal tumors.

Approximately 10% of gastrointestinal stromal tumors (GISTs) harbor reportedly no KIT and PDGFRA mutations (wild-type GISTs). The clinicopathological features and oncologic outcomes of wild-type GISTs based on molecular profiles are unknown. We recruited 35 wild-type GIST patients from the two registry studies of high-risk GISTs between 2012 and 2015 and primary GISTs between 2003 and 2014. Molecular profiling of wild-type GISTs was performed by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tumor samples. Among 35 wild-type GISTs, targeted NGS analysis detected NF1, SDH, or BRAF mutation: 16 NF1-GISTs with various NF1 mutations, 12 SDH-GISTs (4 with SDHA mutations, 4 with SDHB mutations, and 4 with SDHB-negative staining), and 5 BRAF-GISTs with the V600E mutation. Two GISTs showed no mutations based on our targeted NGS analysis. Additional gene mutations were infrequent in primary wild-type GISTs and found in TP53, CREBBP, CDKN2A, and CHEK2. Most NF1-GISTs were located in the small intestine (N = 12; 75%) and showed spindle cell features (N = 15; 94%) and multiple tumors (N = 6, 38%) with modest proliferation activities. In contrast, SDH-GISTs were predominantly found in the stomach (N = 11; 92%), exhibiting epithelioid cell (N = 6; 50%) and multiple (N = 6, 50%) features. The overall survival of patients with SDH-GISTs appeared to be better than that of BRAF-GISTs (p = 0.0107) or NF1-GISTs (p = 0.0754), respectively. In conclusion, major molecular changes in wild-type GISTs include NF1, SDH, and BRAF. NF1-GISTs involved multifocal spindle cell tumors in the small intestine. SDH-GISTs occurred in young patients and were multifocal in the stomach and clinically indolent.

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.

A new methodology to predict the oncotype scores based on clinico-pathological data with similar tumor profiles.

PURPOSE: The Oncotype DX (ODX) test is a commercially available molecular test for breast cancer assay that provides prognostic and predictive breast cancer recurrence information for hormone positive, HER2-negative patients. The aim of this study is to propose a novel methodology to assist physicians in their decision-making. METHODS: A retrospective study between 2012 and 2020 with 333 cases that underwent an ODX assay from three hospitals in the Bourgogne Franche-Comté region (France) was conducted. Clinical and pathological reports were used to collect the data. A methodology based on distributional random forest was developed to predict the ODX score classes (ODX [Formula: see text] and ODX [Formula: see text]) using 9 clinico-pathological characteristics. This methodology can be used particularly to identify the patients of the training cohort that share similarities with the new patient and to predict an estimate of the distribution of the ODX score. RESULTS: The mean age of participants is 56.9 years old. We have correctly classified [Formula: see text] of patients in low risk and [Formula: see text] of patients in high risk. The overall accuracy is [Formula: see text]. The proportion of low risk correct predicted value (PPV) is [Formula: see text]. The percentage of high risk correct predicted value (NPV) is approximately [Formula: see text]. The F1-score and the Area Under Curve (AUC) are of 0.87 and 0.759, respectively. CONCLUSION: The proposed methodology makes it possible to predict the distribution of the ODX score for a patient. This prediction is reinforced by the determination of a family of known patients with follow-up of identical scores. The use of this methodology with the pathologist's expertise on the different histological and immunohistochemical characteristics has a clinical impact to help oncologist in decision-making regarding breast cancer therapy.

Impact of HER2 status on clinicopathological characteristics and pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: HER2-low triple-negative breast cancer (TNBC) accounted for up to 34%-39% of primary TNBC and 22.2%-32% of metastatic TNBC. Our study aims to explore the relationship between HER2 expression and clinicopathological characteristics, analyze the impact of HER2 expression on the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in TNBC. METHODS: This study involved 191 patients with TNBC who underwent operation after NAC from October 2021 to August 2022. Clinicopathological characteristics and the frequency of pCR were compared between HER2-low and HER2-0 TNBC. RESULTS: 42.2% (81/191) patients in our cohort were HER2-low. They exhibited differences in menopausal status, body mass index (BMI), androgen receptor (AR) expression, and histological grade (P < 0.05). Particularly, in HER2-low TNBC, AR was associated with tumor size, lymph node metastase, histological grade, and the incidence of multifocal disease (P < 0.05). The total pCR rate of entire cohor was 39.8%. Tumor size (P = 0.025), AR status (P = 0.033) and histological grade (P = 0.007) were significantly associated with the pCR rate of them, while the HER2 status did not exert a similar association. The multivariate analysis revealed that BMI (P = 0.004) and histological grade (P < 0.001) were associated with pCR of HER2-low TNBC, while tumor size (P = 0.034) and AR (P = 0.034) were associated with pCR of HER2-0 TNBC, respectively. CONCLUSIONS: In our cohort, HER2-low TNBC patients exhibits specific clinical characteristics and response features to NAC.

Helicobacter pylori infection associated DNA methylation in primary gastric cancer significantly correlates with specific molecular and clinicopathological features.

Helicobacter pylori induces DNA methylation in gastric mucosa, which links to gastric cancer (GC) risk. In contrast, CpG island methylator phenotype (CIMP) is defined as high levels of cancer-specific methylation and provides distinct molecular and clinicopathological features of GC. The association between those two types of methylation in GC remains unclear. We examined DNA methylation of well-validated H. pylori infection associated genes in GC and its adjacent mucosa and investigated its association with CIMP, various molecular subtypes and clinical features. We studied 50 candidate loci in 24 gastric samples to identify H. pylori infection associated genes. Identified loci were further examined in 624 gastric tissue from 217 primary GC, 217 adjacent mucosa, and 190 mucosae from cancer-free subjects. We identified five genes (IGF2, SLC16A2, SOX11, P2RX7, and MYOD1) as hypermethylated in H. pylori infected gastric mucosa. In non-neoplastic mucosa, methylation of H. pylori infection associated genes was higher in patients with GC than those without. In primary GC tissues, higher methylation of H. pylori infection associated genes correlated with CIMP-positive and its related features, such as MLH1 methylated cases. On the other hand, GC with lower methylation of these genes presented aggressive clinicopathological features including undifferentiated histopathology, advanced stage at diagnosis. H. pylori infection associated DNA methylation is correlated with CIMP, specific molecular and clinicopathological features in GC, supporting its utility as promising biomarker in this tumor type.

Clinicopathological concordance of mucocutaneous manifestations in people living with HIV: A cross-sectional study.

OBJECTIVE: To describe the frequency and clinicopathological concordance of mucocutaneous manifestations in people living with HIV (PLWH) and its correlation with CD4+ T lymphocyte count and HIV viral load. METHODS: Cross-sectional study of patients diagnosed with HIV infection who underwent skin biopsy for histopathological study from 1992 to 2022. Skin diseases were categorized as opportunistic and sexually transmitted infections, inflammatory dermatoses, benign cutaneous neoplasms, and premalignant and malignant cutaneous neoplasms. Clinicopathological concordance was classified as complete, partial or discordant. Frequency of skin diseases are presented by category and according to lymphocyte CD4+ count and HIV viral load. RESULTS: A total of 659 patients were included of whom 88.5% (n = 583) were male. The most frequent diagnostic category was opportunistic or sexually transmitted infections in 34% (n = 224) and the most frequently found condition was Kaposi sarcoma in 17% (n = 112). Clinicopathological concordance was complete in 53.7% (n = 354) of cases, partial in 26.7% (n = 176) and discordant in 19.6% (n = 129). Among the 282 patients with available serological data, 58.9% (n = 166), 23.8% (n = 67) and 17.4% (n = 49) had CD4+ counts below 200, between 200 and 499, and above 500 cells/µl, respectively. CONCLUSIONS: Although there is a high variability in skin conditions which people with HIV may present, there was a high rate of clinicopathological concordance (80.4%). We emphasize the importance of diagnostic skin biopsies due to their diverse morphological presentation. The frequency of skin diseases in PLWH depending on different clinical settings should aid the clinician in reaching an adequate diagnosis in this population.

Association of the TRIM family protein with survival outcomes and clinicopathological features in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: The tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal cancer (CRC) remains controversial. This study aimed to evaluate the association between TRIM proteins and the clinicopathological features and survival outcomes in patients with CRC. METHODS: We performed a meta-analysis to investigate whether TRIM is a prognostic factor in CRC. PubMed, Embase, Web of Science, CNKI and Weipu databases were searched to identify eligible studies that evaluated the association between TRIM proteins and overall survival (OS), as well as the clinicopathological features of patients with CRC. Hazard ratios (HR) or odds ratios (OR) with 95% confidence interval (CI) were derived and pooled using a fixed-effects model. RESULTS: From inception to March 2023, we extracted study characteristics and prognostic data for each identified study. Twelve studies enrolling 1608 patients were eligible for inclusion. Data on OS and recurrence-free survival (RFS) were available for 12 and 2 studies, respectively. The pooled analysis results showed a significant correlation between the elevated TRIM proteins and shorter OS (HR = 2.42, 95% CI: 1.96-2.99) and worse RFS (HR = 2.51, 95% CI: 1.78-3.54) in patients with CRC. The combined ORs indicated that TRIM protein over-expression was significantly associated with advanced TNM stage (OR = 2.26, 95% CI: 1.25-4.10), deep tumor invasion (OR = 2.01, 95% CI: 1.04-3.88), lymph node metastasis (OR = 2.99, 95% CI: 2.19-4.09) and perineural invasion (OR = 1.95, 95% CI: 1.18-3.23). CONCLUSIONS: Our findings suggest that TRIM proteins can predict tumor progression and poor prognosis in CRC. Therefore, TRIM proteins may be promising therapeutic targets for patients with CRC.

Neuroendocrine carcinoma of the endometrium: a retrospective analysis of data from a single center.

BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. METHODS: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. RESULTS: The median age of the patients was 55.0 (39.0-64.0) years, and the median tumor size was 40.0 (33.0-60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3-81.0) months. Unfortunately, 2 patients died from the disease. CONCLUSION: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.

Frequency of Comorbid Pathologies and Their Clinical Impact in Multiple System Atrophy.

BACKGROUND: Mixed pathology is common at autopsy for a number of age-associated neurodegenerative disorders; however, the frequency of comorbid pathologies in multiple system atrophy (MSA) and their clinical correlations are poorly understood. OBJECTIVE: We determined the frequency of comorbid pathologic processes in autopsy-confirmed MSA and assessed their clinical correlates. METHODS: This study included 160 neuropathologically established MSA from the Mayo Clinic brain bank. Clinical information, including age at onset or death, clinical subtype, initial symptoms, antemortem clinical diagnosis, and cognitive dysfunction was collected. We assessed comorbid pathologies including Alzheimer's disease neuropathologic change, Lewy-related pathology, argyrophilic grain disease, age-related τ astrogliopathy, transactive DNA-binding protein 43 pathology, cerebral amyloid angiopathy, and cerebrovascular small vessel disease and examined their clinical impact. RESULTS: The majority of MSA patients (62%) had no significant comorbid pathologies. There was a positive correlation between age at onset or death with the number of comorbid pathologies; however, even in the highest quartile group (average age at death 78 ± 6 years), the average number of comorbid pathologies was <2. Logistic regression analysis revealed that none of the assessed variables, including sex, age at onset, and the presence or absence of each comorbid pathology, were significantly associated with cognitive dysfunction. CONCLUSIONS: The majority of MSA patients do not have comorbid pathologies, even in advanced age, indicating that MSA is unique among neurodegenerative disorders in this regard. There was minimal clinical impact of comorbid pathologies in MSA. These findings warrant focusing on α-synuclein for the treatment strategy for MSA. © 2023 International Parkinson and Movement Disorder Society.

Clinicopathological analysis of immunohistochemical CD47 and signal-regulatory protein-α expression in Extranodal Natural killer/T-cell lymphoma.

BACKGROUND: The interaction between CD47 and signal-regulatory protein-alpha (SIRPα) inhibits phagocytosis, and their clinicopathological characteristics have been evaluated in various diseases. However, the significance of CD47 and SIRPα expression, as well as the combined effect, in Extranodal Natural killer/T-cell Lymphoma (ENKTL) remains uncertain. METHODS: In total, 76 newly diagnosed ENKTL patients (mean age 49.9 years, 73.7% male) were included in this study. CD47 and SIRPα expression were examined by immunohistochemistry. Survival analyses were conducted through Kaplan-Meier curves and the Cox regression model. RESULTS: Seventy-one (93.4%) cases were categorized as the CD47 positive group and 59 (77.6%) cases were categorized as the SIRPα positive group. CD47-negative cases had more advanced-stage illness (P = 0.001), while SIRPα-positive cases showed significantly lower levels of high-density lipoprotein (P < 0.001). In univariable analysis, CD47, SIRPα expression, and their combination were significantly associated with prognosis (P < 0.05). In multivariable analysis, only positive SIRPα expression remained significantly associated with superior overall survival (Hazard ratio [HR] 0.446; 95% confidence interval [CI] 0.207-0.963; P = 0.004). Furthermore, SIRPα expression could re-stratify the survival of patients in ECOG (< 2), advanced CA stage, PINK (HR), CD38-positive, PD1-positive, and CD30-positive groups. CONCLUSIONS: SIRPα status was a potential independent prognostic factor for ENKTL. The prognostic significance of CD47 expression and the interaction between CD47 and SIRPα in ENKTL need further investigation.

Aberrant cell adhesiveness due to DNA hypermethylation of KLF11 in papillary urothelial carcinomas.

PURPOSE: The aim of this study was to clarify DNA methylation profiles determining the clinicopathological diversity of urothelial carcinomas. METHODS: Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation450 BeadChip in 46 paired samples of non-cancerous urothelium (N) and corresponding cancerous tissue (T), and 26 samples of normal control urothelium obtained from patients without urothelial carcinomas (C). For genes of interest, correlation between DNA methylation and mRNA expression was examined using the Cancer Genome Atlas database. In addition, the role of a selected target for cancer-relevant endpoints was further examined in urothelial carcinoma cell lines. RESULTS: The genes showing significant differences in DNA methylation levels between papillary carcinomas and more aggressive non-papillary (nodular) carcinomas were accumulated in signaling pathways participating in cell adhesion and cytoskeletal remodeling. Five hundred ninety-six methylation sites showed differences in DNA methylation levels between papillary and nodular carcinomas. Of those sites, that were located in CpG-islands around transcription start site, 5'-untranslated region or 1st exon, 16 genes exhibited inverse correlations between DNA methylation and mRNA expression levels. Among the latter, only the KLF11 gene showed papillary T sample-specific DNA hypermethylation in comparison to C and N samples. The DNA methylation levels of KLF11 were not significantly different between T samples and N samples or T samples and C samples for patients with papillo-nodular or nodular carcinomas. Knockdown experiments using the urothelial carcinoma cell lines HT1376 and 5637, which are considered models for papillary carcinoma, revealed that KLF11 participates in altering the adhesiveness of cells to laminin-coated dishes, although cell growth was not affected. CONCLUSION: These data indicate that DNA hypermethylation of KLF11 may participate in the generation of papillary urothelial carcinomas through induction of aberrant cancer cell adhesion to the basement membrane.

A retrospective cross-sectional study: comparison of the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China.

AIM: To analyze the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China and compare them with other areas of the Yangtze River Basin. METHOD: The 501 cases of colorectal cancer (CRC) were retrospectively analyzed from 2020 to 2022. They were divided into two groups: 406 cases of colorectal cancer without schistosomiasis (CRC-NS) and 95 cases of colorectal cancer with schistosomiasis (CRC-S).The clinicopathological characteristics included the distribution of schistosomiasis eggs, patient age, sex, tumor differentiation, lymph node metastasis, and clinical stage. By retrieving the database, this study compared the clinicopathological differences of colorectal cancer with schistosomiasis in other areas of the Yangtze River basin. RESULTS: The cases of colorectal cancer with schistosomiasis accounted for 18.9%(95/501) in the study. The patients of CRC-S were older than the patients of CRC-NS (P = 0.002, P < 0.05). There was a statistical difference in the location of occurrence (P = 0.000, P < 0.05) between the two groups. There were no significant differences between CRC-S and CRC-NS in other clinicopathological features, such as sex (P = 0.054), Type(P = 0.242), histological type(P = 0.654), infiltrative depth(P = 0.811), differentiation(P = 0.837), lymph node metastasis(P = 0.574), intravascular tumor thrombus(P = 0.698), T stage(P = 0.354). In other areas of the Yangtze River Basin, there were statistical differences in the age of occurrence and T stage (P < 0.05) between colorectal cancer with schistosomiasis and non-schistosomal colorectal cancer. CONCLUSION: In Central China, colorectal cancer with chronic schistosomiasis infection occurs more in the rectum and sigmoid colon. It is more common in individuals over 60 years old, consistent with the findings in the Yangtze River Basin. Additionally, schistosomal colorectal cancer had a higher T stage in the Yangtze River Basin. This may be related to the malignant biological behavior of colorectal cancer and could result in a relatively poor prognosis. Therefore, the elderly population in schistosomiasis endemic areas should pay more attention to early screening and tumor prevention.

Association of Fusobacterium nucleatum infection with the clinicopathological characteristics in colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is a global health problem. The gut microbiome is now recognized as an important underlying factor to the initiation and progression of CRC. Fusobacterium nucleatum (FN) is one of the most studied bacteria in the aetiology of CRC. This study provided cohort evidence on the association of FN infection with clinicopathologic features in CRC patients. METHODS: We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted. RESULTS: FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046). CONCLUSIONS: FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

High expression of eukaryotic elongation factor 1-alpha-2 in lung adenocarcinoma is associated with poor prognosis.

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) encodes an isoform of the alpha subunit of the elongation factor 1 complex and is responsible for the enzymatic delivery of aminoacyl tRNA to the ribosome. Our proteomic analysis has identified eEF1A2 as one of the proteins expressed during malignant progression from adenocarcinoma in situ (AIS) to early invasive lung adenocarcinoma. The expression level of eEF1A2 in 175 lung adenocarcinomas was examined by immunohistochemical staining in relation to patient prognosis and clinicopathological factors. Quantitative PCR analysis and fluorescence in situ hybridization (FISH) were performed to evaluate the amplification of the eEF1A2 gene. Relatively high expression of eEF1A2 was observed in invasive adenocarcinoma (39/144 cases) relative to minimally invasive adenocarcinoma (1/10 cases) or AIS (0/21 cases). Among invasive adenocarcinomas, solid-type adenocarcinoma (15/32 cases, 47%) showed higher expression than other histological subtypes (23/92, 25%). Patients with eEF1A2-positive tumors had a significantly poorer prognosis than those with eEF1A2-negative tumors. Of the five tumors that were eEF1A2-positive, two cases showed amplified genomic eEF1A2 DNA, which was confirmed by both qPCR and FISH. These findings indicate that eEF1A2 overexpression occurs in the course of malignant transformation of lung adenocarcinomas and is partly due to eEF1A2 gene amplification.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

Survival and clinicopathological significance of B7-H3 in bladder cancer: a systematic review and meta-analysis.

BACKGROUND: B7-H3 has been implicated in clinical pathological features and prognosis across various cancer types, suggesting its potential as a cancer biomarker. Nevertheless, consensus remains elusive regarding its clinical-pathological and prognostic significance in bladder cancer. To address this gap, we conducted a systematic review and meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane, and CNKI databases from their inception up to October 6, 2022. We evaluated the literature's quality using the Newcastle-Ottawa Scale. We performed meta-analysis using Review Manager 5.3 and STATA 12.0, synthesizing data and calculating odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). RESULTS: After applying eligibility criteria and conducting assessments, we included data from 8 studies, encompassing 1622 bladder cancer patients. Bladder tumor tissues exhibited significantly elevated B7-H3 protein expression compared to normal bladder tissues. Elevated B7-H3 expression was notably associated with patient age, tumor infiltration, and recurrence in bladder cancer. However, no significant correlations were observed with other clinical characteristics. Our pooled HR analysis indicated no significant association between B7-H3 expression and overall survival in bladder cancer patients. CONCLUSION: Our meta-analysis unveils the complex role of B7-H3 in bladder cancer progression. It appears to be directly involved in tumor infiltration and recurrence but cannot definitively serve as a prognostic biomarker for bladder cancer. To validate these findings, further well-designed studies, encompassing larger sample sizes and diverse racial backgrounds, are warranted. PROSPERO REGISTRATION: No. CRD42022364688.

Palmoplantar psoriasis: A clinicopathological correlation in a tertiary care hospital.

BACKGROUND: Palmoplantar psoriasis is a clinical variant of psoriasis characterized by well-defined erythematous desquamating plaques on palms and soles, which may or may not include pustules. Hyperkeratotic lesions of palm and sole commonly include Psoriasis, Eczema and Tinea. These conditions often present with overlapping clinical and histopathological features requiring clinicohistopathological correlation for a conclusive diagnosis. The presence of munro's microabscess or spongiform pustule of kogoj differentiates psoriasis of palm and sole from other hyperkeratotic lesions of palm and sole. The objective of this study was to study the clinical and histopathological profile of palmoplantar psoriasis and correlate clinical diagnosis with histopathological diagnosis. METHOD: A hospital-based, descriptive study was conducted from January 1, 2020, to December 31, 2020. Fifty-two patients were clinically diagnosed as palmoplantar psoriasis with or without involving other parts of body and routine histopathological evaluation was carried out as per standard protocols. RESULT: Clinically diagnosed 52 cases of palmoplantar psoriasis showed varied histopathology with hyperkeratosis (100%), parakeratosis (100%), regular acanthosis (75%), Supra-papillary thinning (44.2%), spongiosis (65.4%), tortuous vessels in the papillary dermis (78.8%) and mixed inflammatory infiltrates (predominantly lymphocytic-100%), which were observed to be prominent findings in skin biopsies of our patients. Clinicopathological correlation was achieved in 88.5% of cases. CONCLUSION: This study shows clinically diagnosed palmoplantar psoriasis with histopathological features consistent with palmoplantar psoriasis in 88.5% cases. Thus, clinically inconclusive hyperkeratotic lesions with palmoplantar psoriasis can be diagnosed with histopathological correlation improving the therapeutic intervention.

Challenges and pitfalls in the diagnosis of IgG4-related disease.

IgG4-related disease (IgG4-RD) is a relatively novel fibroinflammatory condition characterized typically by dense lymphoplasmacytic inflammation, storiform fibrosis and obliterative venulitis, together with prominent IgG4+ plasma cells and an IgG4+/IgG+ plasma cell ratio of >40 %. The diagnosis is usually made on a combination of clinical and serological features together with characteristic radiological and histological appearances. The condition may be limited to a single tissue/organ (e.g., autoimmune pancreatitis) or may be multicentric in nature - four clinical 'patterns' of disease distribution have recently been described. The diagnosis of IgG4-RD can be challenging, particularly when the clinical presentation is unusual and/or when the histological features are not typical. A diagnosis of IgG4-RD may still be achieved in these situations, after careful clinicopathological discussion e.g., at a specialist multidisciplinary team meeting. However, a wide range of other conditions (neoplastic and non-neoplastic) can mimic IgG4-RD, clinically and/or on histological examination. The relationship between IgG4-RD and non-IgG4-RD associated conditions in some clinical situations is particularly complex. This review describes the role of histological examination in the diagnosis of IgG4-RD, discusses some of the practical difficulties that may be encountered and provides an insight into the range of non-IgG4-RD associated conditions that can mimic IgG4-RD on clinical and/or histological grounds. The requirement for interpretation of histological features in the context of the global clinical picture of the patient is highlighted and emphasized.