T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations ...between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.
The expression of DNA fragmentation factor 45 (DFF45) and B-cell lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases of the menstrual cycle and decreases after menopause, ...whereas the expression of DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40 underexpression has been reported in numerous malignancies, including uterine leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40 expression in endometrioid and non-endometrioid types of endometrial cancers (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40 expression levels and clinicopathological parameters and determined the value of these three proteins as prognostic markers of disease-free survival (DFS) and overall survival (OS).
Immunohistochemistry was performed to evaluate DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student's t-test, the Mann-Whitney U-test, and the chi-squared test were used for the statistical analyses as appropriate. The Cox-Mantel test, Cox's proportional hazard model, and relative risk analyses were used to evaluate associations between DFF40, DFF45, and BCL2 expression and clinicopathological characteristics.
DFF40 and BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and high-grade endometrioid ECs compared with low- and moderate-grade endometrioid ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease recurrence, lymph node involvement, lympho-vascular space infiltration, and deep myometrial invasion compared with women with DFF40- and BCL2-positive tumors. Additionally, women with DFF40- and BCL2-negative tumors had significantly lower OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable analysis of the model, including the clinicopathological characteristics and immunohistochemical results, showed that negative BCL2 expression, lymph node involvement, and high-stage and high-grade disease were independent predictors of OS, whereas negative BCL2 expression, lymph node involvement, and high-stage disease were independent predictors of DFS.
Compared with low- and moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2 expression negatively affects DFS and OS. Further prospective studies are warranted to assess the potential utility of DFF40 and BCL2 as targets in the diagnosis or treatment of ECs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A 27-year-old woman with jaundice and abdominal pain was admitted to an emergency ward. The diagnostic process showed that gallstones were causing her symptoms. The patient was treated via endoscopic ...retrograde cholangiopancreatography (ERCP), and during the procedure she suffered a cardiac arrest. Autopsy findings included multiple pulmonary bile emboli as well as features of disseminated intravascular coagulation. Among 22 thus far described cases of bile pulmonary embolism, 13 were associated with medical procedures involving the liver and biliary tract. We present the case report of a pulmonary bile embolism associated with acute pancreatitis treated via ERCP in a woman with gallbladder bile stones.
Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway ...epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (
= 21) vs. no persistent (
= 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g.,
,
,
, and
) and inhibiting apoptosis (e.g., higher mRNA expression of
,
,
, and lower of
,
,
). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (
,
), involved in ECM remodeling (
), neovascularization (
,
), nerve functioning (
,
), oxidative stress adaptation (
,
), epigenetic modifications (
,
), and the innate immune response (
,
). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.
This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 ...tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median age63 y). The tumors involved the right (n=12) and left colon unequally and were either stage T3 (n=12) or T4. Local lymph node and distant metastases were seen at presentation in 6 and 1 patients, respectively. Lymphovascular invasion was present in all cases. Histologically, tumors showed moderate to poor (n=11) differentiation with a partly or entirely solid pattern (n=5) and mucinous component (n=10), including 1 case with sheets of signet ring cells. DNA mismatch repair–deficient phenotype was seen in 13 cases. Tumor-infiltrating CD4/CD8 lymphocytes were prominent in 9 cases. Programmed death-ligand 1 positive tumor-infiltrating immune cells and focal tumor cell positivity were seen in the majority of cases. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 cases. No mutations in BRAF, RAS, and PIK3CA were identified. However, other genes of the PI3K-AKT/MTOR pathway were mutated. In several cases, components of Wnt/β-catenin (APC, AMER1, CTNNB1), p53, and TGFβ (ACVR2A, TGFBR2) pathways were mutated. However, no SMAD4 mutations were found. Two tumors harbored FBXW7 tumor suppressor gene mutations. NTRK fusion tumors constitute a distinct but rare subgroup of colorectal carcinomas.
Mast cells and cancer: enemies or allies? Dyduch, Grzegorz; Kaczmarczyk, Karolina; Okoń, Krzysztof
Polish journal of pathology,
03/2012, Letnik:
63, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Mast cells are a component of cancer microenvironment the role of which is complex and poorly understood. Mast cells promote cancer growth by stimulation of neoangiogenesis, tissue remodeling and by ...modulation of the host immune response. The mediators of cancer promotion include protease-activated receptors, mitogen activated protein kinases, prostaglandins and histamine. Histamine may induce tumor proliferation and immunosuppression through H1 and H2 receptors, respectively. The mast cell-derived modulators of immune response include also interleukin 10 (IL-10), tumor necrosis factor α (TNF-α) and CD30L. Possibly stimulation of angiogenesis is the most important. Mast cells release potent proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGF-β), TNF- α and IL-8, and mast cells' enzymes, like metaloproteinases (MMPs), tryptase and chymase participate in vessels' formation. The anti-cancer actions of mast cells include direct growth inhibition, immunologic stimulation, inhibition of apoptosis and decreased cell mobility; the mediators of these processes include chymase, tryptase, TNF-α, IL-1 and IL-6. The very same mediators may exert both pro- or anti-cancer effects depending on concentration, presence of cofactors or location of secreting cells. In fact, peri- and intra-tumoral mast cells may have dissimilar effects. Understanding of the role of mast cells in cancer could lead to improved prognostication and development of therapeutic methods targeting the mast cells.
Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of ...β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.
Bladder urothelial carcinoma (BC) is a common, recurrent, life-threatening, and unpredictable disease which is difficult to diagnose. These features make it one of the costliest malignancies. ...Although many possible diagnostic methods are available, molecular heterogeneity and difficulties in cytological or histological examination induce an urgent need to improve diagnostic techniques. Herein, we applied Fourier transform infrared spectroscopy in imaging mode (FTIR) to investigate patients’ cytology samples assigned to normal (N), low-grade (LG) and high-grade (HG) BC. With unsupervised hierarchical cluster analysis (UHCA) and hematoxylin-eosin (HE) staining, we observed a correlation between N cell types and morphology. High-glycogen superficial (umbrella) and low-glycogen piriform urothelial cells, both with normal morphology, were observed. Based on the spectra derived from UHCA, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed, indicating a variation of protein content between the patient groups. Moreover, BC spectral cytology identified a low number of high-glycogen cells for which a shift of the carbohydrate/phosphate bands was also observed. Despite high cellular heterogeneity, PLS-DA was able to classify the spectra obtained. The voided urine FTIR cytology is one of the options that might be helpful in BC diagnosis, as high sensitivity and specificity up to 97% were determined.
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