A Morphological and Immunohistochemical Study of the Tumoral and Inflammatory Cells in Pancreatic Ductal Adenocarcinoma (original) (raw)
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Anticancer Research, 2022
Background/Aim: This study evaluated whether circulating lymphocytes, assessed by flow cytometry, is a prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We studied T cell subsets in blood samples from a cohort of 41 patients diagnosed with PDAC. Patients underwent surgery of the primary site and adjuvant chemotherapy or were treated with 1 st line chemotherapy (mFOLFIRINOX regimen or gemcitabine alone). The changes in T cell subpopulations during treatment were evaluated at the initial diagnosis before surgery, and after 2 and 4 months. Friedman test was used for statistical analysis. Results: A decline in CD19+ B lymphocytes, natural killer (NK) cells CD3-CD56+CD16+, and T regulatory cells CD4+FOXP3+ during treatment was observed. NKT-like cells CD3+CD56+ and cytotoxic T cells CD3+CD8+ tended to increase after two months and decrease after that. Conclusion: Statistically significant changes in lymphocyte counts in peripheral blood were detected in patients with PDAC during treatment.
BMC Cancer, 2013
Background Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma. Methods After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features. Results CD3 and CD8 positive lymphocytes...
The effects of systemic inflammatory response on prognosis of pancreatic ductal adenocarcinoma
Annals of Hepato-Biliary-Pancreatic Surgery
Backgrounds/Aims: The aim of this study was to investigate the prognostic significance of neutrophyil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), CRP and CA19-9 in patients were diagnosed with pancreatic ductal adenocarcinoma (PDAC) to better verify pre-operative risk stratification and management. Methods: This retrospective study included data from 133 consecutive patients with PDAC, who were treated between 2013 and 2015. PDAC diagnosis was made by cytology or assumed by radiological assessment or surgical resection samples. All clinico-pathological data were retrieved from medical records at our institution. The laboratory data were obtained before any treatment modality. Dates of death were obtained from the central registry. Results: There was a statistically significant relation between radiological staging and CA19-9 and survival (p=0.001, p=0.005) and there are significant differences in CA19-9 level between stage I and III, I and IV, II and III, and II and IV. Both CRP and CA19-9 levels were statistically significantly higher in patients with radiological lymph node metastasis than patients with N0 disease (p=0.037, p=0.026). NLR and CA19-9 levels were also higher in metastatic disease (p=0.032, p=0.007). According to Spearman's correlation analysis, we found in all patients that there was a negative correlation between the survival time and CRP and neutrophil count (p=0.019, p=0.011). Conclusions: Preoperative CRP, CA19-9 and NLR are simple, repeatable, inexpensive and well available marker, can give information on lymph node and solid organ metastasis and survival, give clues to prognosis and be useful in clinical staging of patients with PDAC.
Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review
PloS one, 2016
A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels ...
PLOS ONE
Background We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes. Methods Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal PLOS ONE |
PLoS ONE, 2014
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive stroma being also present in chronic pancreatitis (CP). Using immunohistochemistry, the stroma of CP and PDAC was comprehensively analyzed and correlated with epithelial/carcinoma-related alterations and clinicopathological patient characteristics. While there were no significant differences between CP and PDAC regarding the distribution of CD3+ T cells and a-SMA+ fibroblasts, proportions of CD4+ and CD8+ T cells were significantly lower and numbers of CD25+(CD4+) and FoxP3+(CD4+) regulatory T cells were greater in PDAC compared with CP. Macrophages were more prevalent in CP, but localized more closely to carcinoma cells in PDAC, as were cd-T cells. Duct-related FoxP3 and L1CAM expression increased from CP to PDAC, while vimentin expression was similarly abundant in both diseases. Moreover, stromal and epithelial compartments of well-differentiated tumors and CPs shared considerable similarities, while moderately and poorly differentiated tumors significantly differed from CP tissues.
Immunohistochemistry of pancreatic neoplasia
Methods in molecular biology (Clifton, N.J.), 2013
Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibody-antigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate...
Current Oncology
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. Methods: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery. Results: A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (p = 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (p = 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (p = 0....
Immuno-histopathological correlations in exocrine pancreatic cancer
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
The CA19-9 antigen is a tumoral marker that can be found in high concentration within a maligned digestive pathology. Objective. Study of CA19-9 antigen from the immunological point of view, at the patients with pancreatic cancer, and his relation with the histopathological aspects. Material and method. The determinations have been done at the time of the diagnosis and after the treatment of the patients with pancreatic cancer (25). Method: indirect ELISA. Results. The values of the CA19-9 marker have been increased at the time of the diagnosis either in pancreatic cancer of the head and mid. At the moment of the diagnosis the CA19-9 marker has higher values (150-400 U/ml) in cancer of the pancreatic body than in cancer of the head of the pancreas (40-200 U/ml). Correlating the size of the tumor with the value of the CA19-9 marker in the case of pancreatic cancer we have been shown the highest serum values (300-400 U/ml) at patients whose tumor was 3 cm bigger. Four weeks post-surgery the CA19-9 values decreased (37-100 U/ml) or reached normal levels (<37 U/ml). At patients with local recurrence or metastasis, especially hepatical, CA19-9 values have increased (100-400 U/ml in case of recurrence and 800 U/ml in case of metastasis). The highest values of the CA 19-9 marker were found in cases of mid pancreas adenocarcinoma. Conclusion. CA19-9 marker values higher than normal cause problems to digestive cancer (especially pancreatic). CA19-9 is a good marker for monitoring of these cancers after treatment; the favorable development is associated with lower values in comparison to the determinations before treatment, or with normal values, unfavorable evolution (local recurrence or metastasis) being associated with very high values. The high values of CA 19-9 suggest an adenocarcinoma.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2016
Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive microenvironment that supports the growth of the malignancy as well as immune system evasion. Here we examine markers of immunosuppression in PDA within the context of the glycolytic tumor microenvironment, their inter-relationship with tumor biology and association with overall survival. We utilized tissue microarrays consisting of 223 PDA patients annotated for clinical stage, tumor size, lymph node involvement, and survival. Expression of CD163, FoxP3, PD-L1, and MCT4 was assessed by immunohistochemistry and statistical associations were evaluated by univariate and multivariate analysis. Multi-marker subtypes were defined by Random Forest analysis. Mechanistic interactions were evaluated using PDA cell lines and models for myeloid differentiation. PDA exhibits discrete expression of CD163, FoxP3 and PD-L1 with modest individual significance. However, combined low expression of these markers was associa...