Prognostic significance of molecular alterations in human pancreatic carcinoma – an immunohistological study

1998 ◽  
Vol 383 (2) ◽  
pp. 152-155 ◽  
Author(s):  
Frank Gansauge ◽  
Susanne Gansauge ◽  
Erika Schmidt ◽  
Jörg Müller ◽  
H. G. Beger
Keyword(s):  
Pancreatic Carcinoma ◽  
Prognostic Significance ◽  
Molecular Alterations ◽  
Immunohistological Study

scholarly journals Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Annamaria Biczok ◽  
Felix L. Strübing ◽  
Julia M. Eder ◽  
Rupert Egensperger ◽  
Oliver Schnell ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Molecular Markers ◽  
Prognostic Significance ◽  
The Elderly ◽  
Molecular Profile ◽  
Diffuse Astrocytoma ◽  
Molecular Alterations ◽  
High Grade Astrocytoma ◽  
Dismal Prognosis ◽  
Few Data

AbstractPrimary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

scholarly journals Systemic immune‐inflammation index has prognostic significance in pancreatic carcinoma patients: a meta-analysis

2021 ◽  
Author(s):  
Xiaocheng Li ◽  
Huapeng Lin ◽  
Renbin Ouyang ◽  
Yaowei Yang ◽  
Jing Peng
Keyword(s):  
Pancreatic Carcinoma ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Cochrane Library ◽  
Cancer Specific Survival ◽  
Non Invasive ◽  
Promising Tool ◽  
Immune Inflammation

Abstract Background Systemic immune-inflammation index (SII) is reportedly a prognostic indicator for several malignancies, including pancreatic carcinoma, although there exists no consensus regarding its significance. In the current study, we used a systematically meta-analysis to evaluate the association between SII and prognosis in pancreatic carcinoma patients. Methods We screened PubMed, Embase and Cochrane Library databases, through May 2020, and retrieved studies describing the prognostic role of SII in pancreatic carcinoma. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) using a random or fixed effects models to reveal the correlation between SII and prognosis. Results A total of 4 studies, comprising 1,749 patients, met our inclusion criteria and were therefore eligible for inclusion. Our meta-analysis showed that elevated SII indicated significantly worse overall survival in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24–1.65, P < 0.001), with subgroup analyses, stratified by the TNM stage and treatment, further validating these results. In addition, patients with high SII had poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55–3.48, P < 0.001). However, we found no significant associations between SII with disease-free and relapse-free survival. Conclusions These findings indicate that SII is a potential non-invasive and promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, further studies using adequate designs and larger sample sizes are required to validate our findings.

La citogenetica e la genetica molecolare nella prognosi del carcinoma della vescica: Cytogenetics and molecular genetics in bladder carcinoma prognosis

1995 ◽  
Vol 62 (2) ◽  
pp. 196-208
Author(s):  
A. D'Amico ◽  
V. Ficarra ◽  
F. Mastroeni ◽  
G. Caleffi ◽  
A. Porcaro ◽  
...  
Keyword(s):  
Molecular Genetics ◽  
Predictive Factors ◽  
Genetic Information ◽  
Tumour Progression ◽  
Prognostic Significance ◽  
Chromosomal Alterations ◽  
Suppressor Genes ◽  
Molecular Alterations ◽  
Bladder Tumours

The use of cytogenetics in the characterization of bladder tumours has made it possible to demonstrate that chromosomal alterations are correlated with stage and grade of the tumour and have a predictive value as regards both tumour recurrences and progression. In the last decade the chromosomes involved in the main aberrations have been identified, and a negative prognostic significance has been suggested for some chromosomal aberrations. The knowledge of cytogenetics has been deepened by the sophisticated methods of molecular genetics, that have discovered many oncogenes and suppressor genes probably involved in the development of bladder tumours. The most characteristic molecular alterations of these tumours are losses of genetic information on chromosomes 9, 11 and 17, as a consequence of deletions and/or mutations. Such alterations probably cause the loss and/or the inactivation of suppressor genes (partly hypothetic still) and could represent important predictive factors of tumour progression.

Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Human Pancreatic Adenocarcinomas: Clinicopathologic and Prognostic Significance of Matrilysin Expression

2001 ◽  
Vol 19 (4) ◽  
pp. 1118-1127 ◽  
Author(s):  
Hiroyuki Yamamoto ◽  
Fumio Itoh ◽  
Shouhei Iku ◽  
Yasushi Adachi ◽  
Hiroshi Fukushima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Matrix Metalloproteinases ◽  
Pancreatic Carcinoma ◽  
Prognostic Significance ◽  
Carcinoma Cells ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Invasive Front ◽  
Clinicopathologic Characteristics ◽  
Tissue Inhibitors

PURPOSE: A disruption in the balance between the matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), has been implicated in the progression of many types of cancer. The aim of this study was to determine whether a specific MMP or TIMP has clinicopathologic and prognostic significance in pancreatic carcinoma. PATIENTS AND METHODS: Using immunohistochemistry, we analyzed 70 pancreatic ductal adenocarcinoma tissues for expression of MMP-1, MMP-2, MMP-3, MMP-7 (matrilysin), MMP-9, MT1-MMP, TIMP-1, and TIMP-2. The results were matched with clinicopathologic characteristics and patients’ survival. The effects of the suppression of a specific MMP on in vitro invasiveness of pancreatic carcinoma cells were also examined. RESULTS: Expression of MMP-1, MMP-2, MMP-3, matrilysin, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 was detected in either tumor cells or tumor stromal cells, or in both components, at varying frequencies. Among MMPs, matrilysin showed a unique distribution in the tumor nests; its expression was usually most pronounced at the invasive front of the tumors. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 40 cases (57%), were judged to be positive for matrilysin. Matrilysin positivity was significantly correlated with pT, pN, and pM categories and with more advanced pathologic tumor-node-metastasis stages. Patients with matrilysin-positive carcinoma had a significantly shorter overall survival time than did those with matrilysin-negative carcinoma. Matrilysin was a significant independent prognostic factor for overall survival in multivariate analysis. In contrast, there was no correlation between the presence of other MMPs or TIMPs and clinicopathologic characteristics, nor was the presence of individual MMPs or TIMPs related to survival. Antisense matrilysin-transfected CFPAC-1 cells expressed reduced levels of matrilysin and demonstrated a similar growth potential but were less invasive in vitro compared with neotransfected CFPAC-1 cells. CONCLUSION: Our results suggest that matrilysin may play a key role in progression of pancreatic carcinoma and thereby contribute to a poor prognosis. Because different synthetic MMP inhibitors affect different types of MMPs to a different degree, examination of the expression of MMPs, especially that of matrilysin, may serve as an indicator for selecting the most effective MMP inhibitor.

Prevalence and Prognostic Implications of WT1 Mutations in Pediatric AML Â: Report from Children’s Oncology Group

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 143-143 ◽  
Author(s):  
Jessica A Pollard ◽  
Rong Zeng ◽  
Phoenix Ho ◽  
Todd Alonzo ◽  
Robert Gerbing ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Direct Sequencing ◽  
Prognostic Significance ◽  
Normal Karyotype ◽  
Wt1 Gene ◽  
Molecular Alterations ◽  
Microcapillary Electrophoresis ◽  
Pediatric Aml ◽  
Wbc Count ◽  
Wt1 Mutation

Abstract Molecular alterations of the WT1 gene have been associated with clinical outcome in adult AML. We evaluated the prevalence and prognostic significance of WT1 mutations in a cohort of 842 pediatric patients treated on pediatric AML trials CCG-2941, CCG-2961, or COG-AAML03P1. Exons 6–10 of the WT1 gene were evaluated by microcapillary electrophoresis and direct sequencing. Of the 842 samples diagnostic specimens analyzed, 68 (8%) contained mutations in exon 7 (n=62), exon 8 (n= 5), or exon 9 (n=1). Correlation analyses were done to determine whether the presence of WT1 mutations is associated with laboratory and disease characteristics and clinical outcome. There were no differences in sex, race, median diagnostic blast %, or median diagnostic WBC count between samples from patients carrying WT1 mutations and those from patients who did not; however, such mutations were less common in the younger patients (age, 0–2 years; p&lt;0.001) and in those with FAB M5 AML (p=0.009). Our evaluation of clinical outcome showed that the rate of complete remission after the first round of induction chemotherapy for those with and without WT1 mutations 74% and 80%, respectively (P=0.3) Actuarial overall survival (OS) from the time of study entry for patients with WT1 mutations was 35% vs. 52% for those without WT1 mutations; p=0.014. Corresponding event-free survival (EFS) was also significantly worse for those with WT1 mutations (27% vs. 41%; p=0.013). We also evaluated associations between WT1 mutations and cytogenetic and molecular alterations. In the patients with WT1 mutations, 31% had inv(16) or t(8;21). There was also substantial overlap between WT1 mutation and FLT3/ITD, i.e., 29% of those carrying a WT1 mutation were FLT3/ITD- positive, whereas only 7% of patients without WT1 were FLT3/ITD-positive (p&lt;0.001). In addition, 11q23 alterations were rare in patients with WT1 mutations (4% vs. 24%; p=0.002). Prognostic significance of WT1 mutations in FLT3/ITD-negative patients was determined. In a comparison of samples from FLT3/ITD-negative patients with WT1 mutations and those from patients who did not carry the 2 mutations, the OS (51% vs. 54%, respectively; p=0.5) and the corresponding EFS (34% and 43%, respectively; p=0.22) were not significantly different. The prognostic significance of the WT1 mutation was also determined in patients with a normal karyotype who were FLT3/ITD-negative. No significant differences were found in the OS (40% and 55%, respectively; p=0.23) or in the corresponding EFS values (31% and 45%, respectively; p=0.335). We conclude that about 8% of children with AML carry WT1 mutations, including novel mutations identified in exon 8. These mutations are associated with other cytogenetic and molecular alterations, and despite their overall association with poor outcome, the prognostic significance of WT1 mutations is less pronounced once the data are corrected for FLT3/ITD and cytogenetic abnormalities.

scholarly journals Prognostic Biomarkers in Pancreatic Cancer: Avoiding Errata When Using the TCGA Dataset

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 126 ◽  
Author(s):  
Remy Nicolle ◽  
Jerome Raffenne ◽  
Valerie Paradis ◽  
Anne Couvelard ◽  
Aurelien de Reynies ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Pancreatic Tumors ◽  
Expression Data ◽  
Web Based ◽  
Molecular Alterations ◽  
Cancer Genome Atlas ◽  
Tcga Dataset

Data from the Cancer Genome Atlas (TCGA) are now easily accessible through web-based platforms with tools to assess the prognostic value of molecular alterations. Pancreatic tumors have heterogeneous biology and aggressiveness ranging from the deadly adenocarcinoma (PDAC) to the better prognosis, neuroendocrine tumors. We assessed the availability of the pancreatic cancer TCGA data (TCGA_PAAD) from several repositories and investigated the nature of each sample and how non-PDAC samples impact prognostic biomarker studies. While the clinical and genomic data (n = 185) were fairly consistent across all repositories, RNAseq profiles varied from 176 to 185. As a result, 35 RNAseq profiles (18.9%) corresponded to a normal, inflamed pancreas or non-PDAC neoplasms. This information was difficult to obtain. By considering gene expression data as continuous values, the expression of the 5312 and 4221 genes were significantly associated with the progression-free and overall survival respectively. Considering the cohort was not curated, only 4 and 14, respectively, had prognostic value in the PDAC-only cohort. Similarly, mutations in key genes or well-described miRNA lost their prognostic significance in the PDAC-only cohort. Therefore, we propose a web-based application to assess biomarkers in the curated TCGA_PAAD dataset. In conclusion, TCGA_PAAD curation is critical to avoid important biological and clinical biases from non-PDAC samples.

scholarly journals Systemic Immune‐Inflammation Index Has Prognostic Significance In Pancreatic Carcinoma Patients: A Meta-Analysis

2020 ◽  
Author(s):  
Xiaocheng Li ◽  
Huapeng Lin ◽  
Renbin Ouyang ◽  
Yaowei Yang ◽  
Jing Peng
Keyword(s):  
Pancreatic Carcinoma ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Cochrane Library ◽  
Cancer Specific Survival ◽  
Non Invasive ◽  
Promising Tool ◽  
Immune Inflammation

Abstract Background: Systemic immune-inflammation index (SII) is reportedly a prognostic indicator for several malignancies, including pancreatic carcinoma, although there exists no consensus regarding its significance. In the current study, we used a systematically meta-analysis to evaluate the association between SII and prognosis in pancreatic carcinoma patients.Methods: We screened PubMed, Embase and Cochrane Library databases, through May 2020, and retrieved studies describing the prognostic role of SII in pancreatic carcinoma. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) using a random or fixed effects models to reveal the correlation between SII and prognosis.Results: A total of 4 studies, comprising 1,749 patients, met our inclusion criteria and were therefore eligible for inclusion. Our meta-analysis showed that elevated SII indicated significantly worse overall survival in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24-1.65, P < 0.001), with subgroup analyses, stratified by the TNM stage and treatment, further validating these results. In addition, patients with high SII had poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55-3.48, P < 0.001). However, we found no significant associations between SII with disease-free and relapse-free survival.Conclusions: These findings indicate that SII is a potential non-invasive and promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, further studies using adequate designs and larger sample sizes are required to validate our findings.

scholarly journals Prognostic significance of the systemic immune-inflammation index in pancreatic carcinoma patients: A meta-analysis

2021 ◽  
Author(s):  
Xiaocheng Li ◽  
Huapeng Lin ◽  
Renbin Ouyang ◽  
Yaowei Yang ◽  
Jing Peng
Keyword(s):  
Pancreatic Carcinoma ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Cochrane Library ◽  
Cancer Specific Survival ◽  
Non Invasive ◽  
Promising Tool ◽  
Immune Inflammation

Background: Systemic immune-inflammation index (SII) is a prognostic indicator for several malignancies, including pancreatic carcinoma, however, there is no consensus on its significance. In the current study, a systematic meta-analysis was used to explore the correlation between SII and prognosis in pancreatic carcinoma patients. Methods: PubMed, Embase and Cochrane Library databases were screened from inception to May 2020. Studies describing the prognostic role of SII in pancreatic carcinoma were then retrieved. The pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated using random or fixed effects models to determine the correlation between SII and prognosis. Results: A total of 4 studies, comprising 1,749 patients, met the inclusion criteria of the study and were therefore included in this meta-analysis. The meta-analysis showed that high SII indicated was correlated with worse overall survival in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24-1.65, P &lt; 0.001). These findings were validated through subgroup analyses, stratified by the AJCC stage. In addition, patients with high SII showed poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55-3.48, P &lt; 0.001). However, analysis showed no significant correlations between SII and disease-free and relapse-free survival. Conclusion: These findings indicate that SII is a potential non-invasive and a promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, the current research did not explore whether neoadjuvant therapy has an effect on the prognostic value of SII. Further studies using adequate designs and larger sample sizes are required to validate these findings.

scholarly journals Diagnostic and Prognostic Significance of CA 19-9 as Tumour Marker in Pancreatic, Hepatobiliary and Other Gastrointestinal Cancers

2021 ◽  
Author(s):  
Mitsu Vinay Vaishnav ◽  
Sameep Shyamlal Garg ◽  
Mayur Jitubhai Kokani
Keyword(s):  
Pancreatic Carcinoma ◽  
Predictive Value ◽  
Tertiary Care ◽  
Prognostic Significance ◽  
Tumour Marker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Care Hospital ◽  
Prognostic Information ◽  
Cross Sectional

Introduction: The CA 19-9 antigen isolated by Koprowski and colleagues in 1979 is a lacto-N-fucopentaose II-like substance and one of the tumour-associated antigens present in serum in the mucin fraction. Close attention has been paid to the role CA 19-9 in the diagnosis of digestive tract tumours. In this study, serum analysis of CA 19-9 levels in 91 patients with gastrointestinal, hepatobiliary and pancreatic carcinoma was done. These data was used to evaluate the clinicians with adequate information on use of CA 19-9 as tumour marker- both diagnostic and prognostic. Aim: To study the role of tumour marker, CA 19-9 as a diagnostic and prognostic tool, and also to monitor the response of gastrointestinal, hepatobiliary and pancreatic cancer to treatment. Materials and Methods: This cross-sectional study was done on 91 cases of gastrointestinal, hepatobiliary and pancreatic carcinomas conducted in tertiary care hospital associated with medical college in Jamnagar, Gujarat, India were studied from September 2012 to March 2015 for two years and five months. The sample size was of 91 patients. Statistical method used was sensitivity, specificity, positive predictive value and negative predictive value. The material used was serum of the patient both pre as well as postoperatively and CalBiotech CA 19-9 Elisa Kit was used to determine the Value. The collected data were entered into Microsoft Excel spread sheet. The statistical methods used for variables were Mean and median along with Sensitivity and Specificity. Software used was “Epi Info”, version 7.0. Results: Total 91 cases of gastrointestinal, hepatobiliary and pancreatic carcinomas were studied. Enzyme Linked Immunosorbent Assay (ELISA) was used preoperatively and post operatively to determine the CA 19-9 values in patients of gastrointestinal, hepatobiliary and pancreatic carcinomas. It was found that CA 19-9 is an important tumour marker with sensitivity of 76.31% and specificity of 73.33% for diagnosis of the gastrointestinal, hepatobiliary and pancreatic carcinoma. When aided with Fine Needle Aspiration Cytology (FNAC) and histopathological findings it helps in giving a sure shot diagnosis. It also provides useful prognostic information for the same. Conclusion: This study helps to understand the role of CA 19-9 as diagnostic and prognostic marker for pancreatic, hepatobiliary and gastrointestinal carcinomas.

Prognostic Significance of DNA Ploidy in Pancreatic Carcinoma

Pancreas ◽  
1994 ◽  
Vol 9 (6) ◽  
pp. 764-772 ◽  
Author(s):  
Stefan Linder ◽  
Ursula Falkmer ◽  
Torbjörn Hagmar ◽  
Margareta Blåsjö ◽  
Pär Sundelin ◽  
...  
Keyword(s):  
Pancreatic Carcinoma ◽  
Dna Ploidy ◽  
Prognostic Significance
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