Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation.
Ontology highlight
ABSTRACT: Background
Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC).Methods
We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC.Results
Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (κ-value of 0.87).Conclusion
Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients.
SUBMITTER: Hiraoka N
PROVIDER: S-EPMC2965866 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The pathological prognostic factors in pancreatic cancer patients who have received neoadjuvant therapy (NAT) are still elusive. The aim of the present study was to investigate the prognostic potential of histological tumor necrosis (HTN) in patients who received NAT and to evaluate tumor changes after NAT. HTN was studied in 44 pancreatic cancer patients who received NAT followed by surgery (NAT group) compared with 263 patients who received upfront surgery (UFS group). The prognostic factors in the NAT group were analyzed, and carbonic anhydrase 9 (CA‑9) expression was compared between the NAT and USF group to evaluate the hypoxic microenvironment changes during NAT. HTN was found in 15 of 44 patients in the NAT group, and its frequency was lower than that in the UFS group (34 vs. 51%, P=0.04). Cox proportional hazards models identified HTN as an independent risk factor for relapse‑free survival in the NAT group [risk ratio (RR), 5.60; 95% confidence interval (CI): 2.27‑14.26, P<0.01]. Significant correlations were found between HTN and CA‑9 expression both in the NAT and UFS groups (P<0.01 for both). CA‑9 expression was significantly upregulated in the NAT group overall, although this upregulation was specifically induced in patients without HTN. In conclusion, HTN was a poor prognostic factor in pancreatic cancer patients receiving NAT followed by surgery, and the present study suggests a close association between HTN and tumor hypoxia. Increased hypoxia after NAT may support the thesis for re‑engineering the hypoxia‑alleviating tumor microenvironment in NAT regimens for pancreatic cancer.
| S-EPMC9164264 | biostudies-literature
Project description:Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&E) and pancytokeratin. Tumor budding was scored by independent observers at five participating centers in Switzerland, Germany, and Canada. Pathologists assessed tumor budding on a digital platform comparing H&E with pancytokeratin staining in 10 high-power fields (10HPF) and one HPF hotspot (1HPF). Additionally, tumor budding was assessed in one H&E hotspot at × 20 magnification, as suggested by the International Tumor Budding Consensus Conference (ITBCC). Correlation coefficients for bud counts between centers ranged from r = 0.58648 to r = 0.78641 for H&E and from r = 0.69288 to r = 0.81764 for pancytokeratin. The highest interobserver agreement across all centers was observed for pancytokeratin 10HPFs (ICC = 0.6). ICC values were 0.49, 0.48, 0.41, and 0.4 for H&E in 1HPF hotspot, H&E in 10HPFs, pancytokeratin in 1HPF, and H&E in one hotspot at ×20, respectively (ITBCC method). This interobserver study reveals a range between moderately poor to moderate agreement levels between pathologists for the different tumor budding assessment methods in PDAC. Acceptable levels of agreement were reached with the pancytokeratin 10HPF method, which can thus be recommended for the assessment of tumor budding in PDAC resection specimens. To improve the levels of interobserver agreement, the implementation of machine learning applications should be considered.
| S-EPMC7990816 | biostudies-literature
Project description:Podocalyxin overexpression associates with poor survival in pancreatic cancer (PDAC). We investigated whether podocalyxin expression correlates with treatment response or survival in neoadjuvant-treated PDAC. Through immunohistochemistry, we evaluated podocalyxin expression in 88 neoadjuvant and 143 upfront surgery patients using two antibodies. We developed a six-tier grading scheme for neoadjuvant responses evaluating the remaining tumor cells in surgical specimens. Strong podocalyxin immunopositivity associated with poor survival in the patients responding poorly to the neoadjuvant treatment (HR 4.16, 95% CI 1.56-11.01, p = 0.004), although neoadjuvant patients exhibited generally low podocalyxin expression (p = 0.017). Strong podocalyxin expression associated with perineural invasion (p = 0.003) and lack of radiation (p = 0.036). Two patients exhibited a complete neoadjuvant response, while a strong neoadjuvant response (≤ 5% of residual tumor cells) significantly associated with lower stage, pT-class and grade, less spread to the regional lymph nodes, less perineural invasion, and podocalyxin negativity (p < 0.05, respectively). A strong response predicted better survival (HR 0.28, 95% CI 0.09-0.94, p = 0.039). In conclusion, strong podocalyxin expression associates with poor survival among poorly responding neoadjuvant patients. A good response associates with podocalyxin negativity. A strong response associates with better outcome.
| S-EPMC8110523 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC.MethodsThree independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined.ResultsHigher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68-6.17, Ptrend < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour.ConclusionsOur results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.
| S-EPMC10241859 | biostudies-literature
Project description:The Ki-67 Labelling Index (LI) is used as an ancillary tool in glioma diagnostics. Interobserver variability has been reported and no precise guidelines are available. Nor is it known whether novel digital approaches would be an advantage. Our aim was to evaluate the inter- and intraobserver variability of the Ki-67 LI between two pathologists and between pathologists and digital quantification both in whole tumour slides and in hot spots using narrow but diagnostically relevant intervals.In samples of 235 low and high grade gliomas, two pathologists (A and B) estimated the Ki-67 LI (5-10% intervals) for whole tumour slides and for hot spots. In 20 of the cases intraobserver variability was evaluated. For digital quantification (C) slides were scanned with subsequent systematic random sampling of viable tumour areas. A software classifier trained to identify positive and negative nuclei calculated the Ki-67 LI. The interobserver agreements were evaluated using kappa (?) statistics.The observed proportions of agreement and ? values for Ki-67 LI for whole tumour slides were: A/B: 46% (??=?0.32); A/C: 37% (??=?0.26); B/C: 37% (??=?0.26). For hot spots equivalent values were: A/B: 14% (??=?0.04); A/C: 18% (??=?0.09); B/C: 31% (??=?0.21).Interobserver variability was pronounced between pathologists and for pathologists versus digital quantification when attempting to estimate a precise value of the Ki-67 LI. Ki-67 LI should therefore be used with caution and should not be over interpreted in the grading of gliomas. Digital quantification of Ki-67 LI in gliomas was feasible, but intra- and interlaboratory robustness need to be determined.
| S-EPMC5994254 | biostudies-other
Project description:Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.
| S-EPMC6722558 | biostudies-other
Project description:BackgroundALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been suggested to have a relevant impact on tumour invasion. Although the expression of ALCAM is a valuable prognostic and predictive marker in several types of epithelial tumours, its role as a prognostic marker in pancreatic cancer has not yet been reported.MethodsIn this study, paraffin-embedded samples of 97 patients with pancreatic cancer undergoing potentially curative resection were immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was semiquantitatively evaluated and correlated to clinical and histopathological parameters.ResultsWe could show that in normal pancreatic tissue, ALCAM is predominantly expressed at the cellular membrane, whereas in pancreatic tumour cells, it is mainly localised in the cytoplasm. In addition, univariate and multivariate analyses show that increased expression of ALCAM is an adverse prognostic factor for recurrence-free and overall survival. Overexpression of ADAM17 in pancreatic cancer, however, failed to be a significant prognostic marker and was not coexpressed with ALCAM.ConclusionsOur findings support the hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer.
| S-EPMC2720248 | biostudies-literature
Project description:Pancreatic adenocarcinoma (PAAD) is a major threat to people's health. PRDM1 is a transcription factor with multiple functions, and its functions have been validated in a variety of tumors; however, there are few studies reported on PRDM1 in PAAD. Using the GEPIA2 database, this research found that PRDM1 expression in PAAD was significantly higher than that in normal pancreatic tissue. The Kaplan-Meier Plotter database showed that high expression of PRDM1 in PAAD has a poor prognosis, suggesting that PRDM1 may be a potential prognostic marker in PAAD. The cBioPortal database shows that the expression of PRDM1 in PAAD is significantly correlated with its methylation degree. Further analysis on the coexpressed genes of PRDM1 in PAAD was performed by using LinkedOmics database to explore potential mechanisms. Based on gene enrichment analysis, PRDM1 was implicated in many pathways involved in tumor progression. In the construction of a PPI network of PRDM1 and its coexpressed gene protein via the STRING database, we found that PRDM1 may be involved in the pathogenesis and development of PAAD. TIMER database suggested that a high level of PRDM1 has a significant positive correlation with macrophages, neutrophils, and DCs. Potential methylation sites of PRDM1 were found through DNMIVD database, and MethSurv database explored eight sites which were significantly related with the prognosis of PAAD. In conclusion, PRDM1 may work as a prognostic marker or even provide a potential therapeutic strategy in PAAD.
| S-EPMC9123419 | biostudies-literature
Project description:BackgroundKi67 labeling index (LI) is used as a predictive marker and is associated with prognosis in breast cancer. However, standardised methodologies for measurement are lacking which has limited its application in clinical practice. In this study, we evaluated the interobserver concordance of visual assessment of Ki67 LI in breast cancer.MethodsKi67-immunostained slides of 160 cases of primary invasive breast cancer were visual assessed by five breast pathologists with two different methods to choose the scoring fields: (1) hot-spot score, (2) average score. Proportions of positive invasive tumor cells at 10 % intervals were scored. The intra-class correlation coefficient (ICC) was used to assess the interobserver reproducibility.Results(1) A perfect concordance of Ki67 LI was demonstrated according to both score methods (P<0.0001). Average score method (ICC, 0.904) demonstrated a better correlation than hot-spot score method (ICC, 0.894). (2) By respective means according to two score methods, all cases were classified into three groups (?10%, 11%-30% and >30% Ki-67 LI). The concordance was relatively low in intermediate Ki67 LI group compared with low and high Ki67 LI groups. (3) All cases were classified into three groups by paired-difference (d) between means of hot-spot score and average score (d<5, 5?d<10, d?10). The consistency was observed to decrease with increasing paired-difference according to both methods.ConclusionsVisual assessment of Ki67 LI at 10 % intervals is a candidate for a standard method in breast cancer clinical practice. Average score and hot-spot score of visual assessment both demonstrated a perfect concordance, and an overall average assessment across the whole section including hot spots may be a better method. Interobserver concordance of intermediate Ki67 LI in which most cutoffs are located for making clinical decisions was relatively low.
| S-EPMC4416820 | biostudies-literature
Project description:The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm).Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management.The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact.Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.
| S-EPMC5545779 | biostudies-other