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Background/Objectives: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Methods: Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. Results: In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. Conclusions: In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging. [ABSTRACT FROM AUTHOR]

Simple Summary: Current clinical practice guidelines support additional locoregional surgery after local resection of early colorectal cancer when one or more of the following risk factors are present: poor differentiation grade, lymphovascular invasion, deep submucosal invasion, moderate or high tumor budding, and deep margin involvement. The absence of all these risk criteria selects a subgroup of patients with very good prognosis that can safely avoid additional surgery. However, lymph node metastases are only identified in 10–20% of patients who ultimately undergo additional surgery, so that 80–90% of the surgeries turn out to be unnecessary. In this investigation, we find that indicating additional surgery in early colorectal cancer only when either moderate or high tumor budding, poorly differentiated clusters, or lymphovascular invasion are present could reduce unnecessary surgeries by 40–45% without significantly increasing the proportion of patients with lymph node metastases who are not offered additional surgery. Background: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Methods: Logistic regression analysis was performed to determine the association of diverse variables with LNM or 'poor outcome' (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. Results: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717–0.880) compared to 0.582 (CI 95% 0.479–0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with 'poor outcome', with an AUC of 0.801 (CI 95% 0.731–0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603–0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. Conclusions: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly. [ABSTRACT FROM AUTHOR]

We explored the added value of a radiomic strategy based on quantitative transverse relaxation (T2) mapping and conventional magnetic resonance imaging (MRI) to evaluate the histologic grade of bladder cancer (BCa) preoperatively. Patients who were suspected of BCa underwent pelvic MRI (including T2 mapping and diffusion-weighted imaging (DWI) before any treatment. All patients with histological-proved urothelial BCa were included. We constructed different prediction models using the mean signal values and radiomic features from both T2 mapping and apparent diffusion coefficient (ADC) maps. The diagnostic performance of each model or parameter was assessed using receiver operating characteristic curves. In total, 92 patients were finally included (training cohort, n = 64; testing cohort, n = 28); among these, 71 had high-grade BCa. In the testing cohort, the T2-mapping radiomic model achieved the highest prediction performance (area under the curve (AUC), 0.87; 95% confidence interval (CI), 0.73–1.0) compared with the ADC radiomic model (AUC, 0.77; 95%CI, 0.56–0.97), and the joint radiomic model of 0.78 (95%CI, 0.61–0.96). Our results demonstrated that radiomic mapping could provide more information than direct evaluation of T2 and ADC values in differentiating histological grades of BCa. Additionally, among the radiomic models, the T2-mapping radiomic model outperformed the ADC and joint radiomic models. [ABSTRACT FROM AUTHOR]

The chemoattractant protein chemerin is protective in experimental hepatocellular carcinoma (HCC), and high expression in HCC tissues of Asian patients was related to a favorable prognosis. Studies from Asia found reduced expression of chemerin in HCC compared to para-tumor tissues while our previous analysis observed the opposite. Aim of this study was to correlate chemerin expression in HCC tissues with disease severity of European patients Hepatocyte chemerin protein expression was assessed by immunohistochemistry in HCC tissue of 383 patients, and was low in 24%, moderate in 49% and high in 27%. High chemerin protein in the HCC tissues was related to the T stage, vessel invasion, histologic grade, Union for International Cancer Control (UICC) stage and tumor size. Chemokine-like receptor 1 (CMKLR1) is a functional chemerin receptor. CMKLR1 protein in hepatocytes was low expressed in HCC tissues of 36%, moderate in tissues of 32% and high in 32% of the HCCs. Tumor CMKLR1 was associated with the T stage, vessel invasion, histologic grade and UICC stage. Notably, sex-specific analysis revealed that associations of chemerin and CMKLR1 expression with HCC progression were significant in males but not in females. The tumor chemerin and CMKLR1 protein expression were not related to steatosis, inflammation and fibrosis grades. In summary, chemerin as well as CMKLR1 protein were related to disease severity of European HCC patients, and this was significant in males. This observation is in contrast to Asian patients where higher chemerin in the tumors was protective. Current analysis provides evidence for ethnicity and sex-related differences of tumor expressed chemerin and HCC severity. [ABSTRACT FROM AUTHOR]

Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations. We performed both univariate and multivariable logistic regressions to identify predictors of EGFR mutations. We found that histologic grade was significantly associated with the incidence of EGFR mutation, regardless of ethnicity, sex and smoking status. In grade I (well differentiated) and II (moderately differentiated), histology was associated with significantly higher incidence of EGFR mutations compared to grade II-III (moderate-to-poorly differentiated) and III (poorly differentiated). Ever-smokers with grade III lung adenocarcinoma had 1.8% incidence of EGFR mutations. This study indicates that histologic grade is a predictive factor for the incidence of EGFR mutations and suggests that for patients with grade II-III or III lung adenocarcinoma, prompt initiation of first-line chemotherapy or immunotherapy is appropriate while awaiting results of EGFR mutational analysis, particularly for patients with history of smoking. [ABSTRACT FROM AUTHOR]

Simple Summary: Confirming whether a breast lesion is benign or malignant usually involves an invasive tissue sample with an image-guided breast biopsy, which may cause substantial inconvenience to the patient. The purpose of this study was to investigate whether imaging biomarkers obtained from noninvasive dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast can help differentiate benign from malignant lesions and characterize breast cancers to the same extent as a biopsy. In a sample of 37 patients with suspicious findings on mammography or ultrasound, we found that the radiologists' diagnostic accuracy was improved when subjective Breast Imaging-Reporting and Data System (BI-RADS) evaluation was augmented with the use of pharmacokinetic markers. This study serves as a starting point for future collaborative research with the potential of providing valuable noninvasive tools for improved breast cancer diagnosis. The purpose of this study was to investigate whether ultra-high-field dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast at 7T using quantitative pharmacokinetic (PK) analysis can differentiate between benign and malignant breast tumors for improved breast cancer diagnosis and to predict molecular subtypes, histologic grade, and proliferation rate in breast cancer. In this prospective study, 37 patients with 43 lesions suspicious on mammography or ultrasound underwent bilateral DCE-MRI of the breast at 7T. PK parameters (KTrans, kep, Ve) were evaluated with two region of interest (ROI) approaches (2D whole-tumor ROI or 2D 10 mm standardized ROI) manually drawn by two readers (senior reader, R1, and R2) independently. Histopathology served as the reference standard. PK parameters differentiated benign and malignant lesions (n = 16, 27, respectively) with good accuracy (AUCs = 0.655–0.762). The addition of quantitative PK analysis to subjective BI-RADS classification improved breast cancer detection from 88.4% to 97.7% for R1 and 86.04% to 97.67% for R2. Different ROI approaches did not influence diagnostic accuracy for both readers. Except for KTrans for whole-tumor ROI for R2, none of the PK parameters were valuable to predict molecular subtypes, histologic grade, or proliferation rate in breast cancer. In conclusion, PK-enhanced BI-RADS is promising for the noninvasive differentiation of benign and malignant breast tumors. [ABSTRACT FROM AUTHOR]

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan-Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients' cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.