Search

Background: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy. [ABSTRACT FROM AUTHOR]

Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. Methods: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. Results: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. Conclusions: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of the reticuloendothelial system, including the bone marrow (BM) and spleen, on positron emission tomography/computed tomography (PET/CT) has been shown to be a significant prognostic factor in diverse malignancies. However, the relationship between FDG uptake of the BM and spleen and histopathological findings, including the tumor immune microenvironment, has not been fully evaluated. This study aimed to investigate the relationship of FDG uptake in the BM and spleen with histopathological findings and recurrence-free survival (RFS) in patients with gastric cancer. Seventy patients with gastric cancer who underwent pre-operative FDG PET/CT and subsequent curative surgery were retrospectively enrolled. On image analysis, the BM-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) were measured from PET/CT images, and on immunohistochemical analysis, the densities of immune cell infiltration in the tumor tissue were graded. The BLR and SLR showed significant positive correlations with the grades of CD163 cell and CD8 cell infiltration in the tumor tissue, respectively (p < 0.05). In multivariate survival analysis, both BLR and SLR were significant predictors of RFS (p < 0.05). FDG uptake in the BM and spleen might be potential imaging biomarkers for evaluating tumor immune microenvironment conditions and predicting RFS in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiomic analysis using textural features extracted from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images was performed to precisely predict metastasis and prognosis in patients with gastric cancer. However, the relationship between FDG PET/CT textural features and histopathological findings in gastric cancer has not been fully evaluated. This study investigated the textural features of gastric cancer on staging FDG PET/CT images with histopathological findings, including components of the immune microenvironment, and recurrence-free survival (RFS) after curative surgery. Textural features were associated with the histopathological classification, Lauren classification, the pN stage of gastric cancer, CD8 T lymphocytes, macrophage infiltrations, and matrix-metalloproteinase-11 expression in the tumor tissue. Textural features were significantly associated with RFS. Textural features of gastric cancer on FDG PET/CT could provide information regarding the histopathological features of cancer cells and the immune microenvironment, and they could be used to predict RFS. The relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) textural features and histopathological findings in gastric cancer has not been fully evaluated. We investigated the relationship between the textural features of primary tumors on FDG PET/CT with histopathological findings and recurrence-free survival (RFS) in patients with advanced gastric cancer (AGC). Fifty-six patients with AGC who underwent FDG PET/CT for staging work-ups were retrospectively enrolled. Conventional parameters and the first- and second-order textural features of AGC were extracted using PET textural analysis. Upon histopathological analysis, along with histopathological classification and staging, the degree of CD4, CD8, and CD163 cell infiltrations and expressions of interleukin-6 and matrix-metalloproteinase-11 (MMP-11) in the primary tumor were assessed. The histopathological classification, Lauren classification, lymph node metastasis, CD8 T lymphocyte and CD163 macrophage infiltrations, and MMP-11 expression were significantly associated with the textural features of AGC. The multivariate survival analysis showed that increased FDG uptake and intra-tumoral metabolic heterogeneity were significantly associated with an increased risk of recurrence after curative surgery. Textural features of AGC on FDG PET/CT showed significant correlations with the inflammatory response in the tumor microenvironment and histopathological features of AGC, and they showed significant prognostic values for predicting RFS. [ABSTRACT FROM AUTHOR]

Background Melanoma of unknown primary (MUP) is a condition of metastatic melanoma without a primary lesion. Objective We sought to identify the prognosis of MUP compared with melanoma of known primary (MKP). Methods We searched for observational studies containing at least 10 patients with MUP from MEDLINE and EMBASE from inception to December 22, 2012. The outcomes of interest were overall and disease-free survival; meta-analyses of hazard ratio stratified by stage using a random effects model were performed. In addition, second systematic review identified risk factors influencing the survival of patients with MUP. Results Eighteen studies including 2084 patients with MUP and 5894 with MKP were included. MUP had a better overall survival compared with MKP in stage III (15 studies; hazard ratio 0.83, 95% confidence interval 0.73-0.96, P = .010) and stage IV (6 studies; hazard ratio 0.85, 95% confidence interval 0.75-0.96, P = .008). Secondly, 22 studies including 3312 patients with MUP were reviewed, and increased stage and old age were the risk factors in patients with MUP. Limitations Diverse observational studies were reviewed, and selection and reporting biases are possible. Conclusions The current meta-analyses suggest better survival outcomes in patients with MUP than those in patients with MKP with the same corresponding tumor stage. [ABSTRACT FROM AUTHOR]

Background The reported mortality rates and prognoses of bullous pemphigoid (BP) vary among different countries. However, the mortality rate of BP has not been investigated in Korea. Objective We sought to evaluate the mortality rate of Korean patients with BP in comparison to that of an age-matched general population in Korea, and to identify prognostic factors affecting overall survival. Methods We conducted a retrospective analysis of 168 patients diagnosed with BP between 1993 and 2013 at Gangnam Severance Hospital in Seoul, Korea. Results The 1-, 2-, and 5-year mortality rates of BP patients were 19.46% (95% confidence interval [CI], 13.83-27.00), 29.13% (95% CI, 21.91-38.08), and 58.03% (95% CI, 47.04-69.45), respectively. The median age was 73 years (range, 6-99 years). The standardized mortality ratio ranged from 2.43 (95% CI, 0.12-11.96) to 9.56 (95% CI, 2.43-26.02), depending on the age group. In multivariate analysis, old age at the time of diagnosis, stroke, diabetes, and delayed diagnosis were associated with increased mortality. Limitations This study was conducted as a retrospective analysis and was based at a single institution. Conclusion The mortality rate of patients with BP is significantly higher than that for the general population. [ABSTRACT FROM AUTHOR]

Adenine-thymine-rich inactive domain-containing protein 1A (ARID1A) is a large subunit of the switch-sucrose nonfermenting (SWI-SNF) complex. ARID1A is considered to be a tumor suppressor in various cancers. We investigated the clinicopathological significance including prognosis of ARID1A expression in non-small cell lung cancer (NSCLC). ARID1A expression was studied by tissue microarray immunohistochemical analysis of 171 surgically resected NSCLC specimens including adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on tissue microarray. Semiquantitative immunohistochemical score was obtained by multiplying the intensity and percentage scores. The overall score was further simplified by dichotomizing into either negative (score < 4) or positive (score ≥ 4) for each patient. The ARID1A-negative group revealed significantly higher correlations with male sex (p = 0.020), larger tumor size (p = 0.007), SCC than with ADC (p = 0.023) and smoking (p = 0.001). Univariate survival analysis showed that the ARID1A-negative group had a significantly shorter cancer specific survival than the ARID1A-positive group (p = 0.018). Multivariate survival analysis showed that ARID1A negativity (p = 0.022) were independent prognostic factors related with shorter cancer specific survival for NSCLC. In conclusion, Loss of ARID1A expression is a potential molecular marker to predictive of poor prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the relationship of imaging features of primary tumor and peritumoral VAT on PET/CT with histopathological findings of peritumoral VAT and recurrence-free survival (RFS) in patients with colorectal cancer.Methods: We retrospectively reviewed 133 patients diagnosed with colorectal cancer who underwent staging FDG PET/CT and received curative surgery. Histogram-based imaging features of primary tumor and peritumoral VAT were extracted from PET/CT images. Based on histopathological analysis of peritumoral VAT, the degree of CD4, CD8, and CD163 cell infiltration and the expression of matrix metalloproteinase-11 and interleukin 6 (IL-6) were graded. Differences in imaging parameters based on the histopathological results and the relationships between imaging features and RFS were assessed.Results: Mean CT-attenuation and SUV of peritumoral VAT showed significant positive correlation with CD163 cell infiltration and IL-6 expression of peritumoral VAT. Univariable survival analysis revealed significant correlation between RFS and the mean CT-attenuation, mean SUV, and first-order SUV entropy of peritumoral VAT (p < 0.05). Multivariable analysis indicated that mean SUV and SUV entropy of peritumoral VAT remained significant predictors of RFS after adjustment for age, sex, and T stage (p < 0.05).Conclusion: FDG uptake of peritumoral VAT was significantly associated with inflammatory response in peritumoral VAT and was an independent predictor of RFS in colorectal cancer patients. [ABSTRACT FROM AUTHOR]