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Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation.

Hiraoka N, Ino Y, Sekine S, Tsuda H, Shimada K, Kosuge T, Zavada J, Yoshida M, Yamada K, Koyama T, Kanai Y - Br. J. Cancer (2010)

Bottom Line: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype.The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC.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.

View Article: PubMed Central - PubMed

Affiliation: Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. nhiraoka@ncc.go.jp

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.

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Kaplan–Meier survival curves showing the comparison of disease-free survival between high and low expression of CAIX (P-values obtained from log-rank test) (left columns). Kaplan–Meier survival curves showing the comparison of disease-specific survival between high and low expression of CAIX (P-values obtained from log-rank test) (right columns).
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fig3: Kaplan–Meier survival curves showing the comparison of disease-free survival between high and low expression of CAIX (P-values obtained from log-rank test) (left columns). Kaplan–Meier survival curves showing the comparison of disease-specific survival between high and low expression of CAIX (P-values obtained from log-rank test) (right columns).

Mentions: Survival analysis showed that the presence of hypoxic foci with expression of CAIX in stromal cells in cancer tissue was closely associated with shorter DFS (P=0.004) and DSS (P=0.003) (Figure 3). The presence of cancer cells expressing CAIX was also associated with shorter survival rates (Figure 3), although its occasional expression in cancer cells forming well-differentiated glands distant from necrotic areas probably indicated a cellular phenotype similar to that of normal ductal epithelial cells, and was unrelated to hypoxia. Then we used expression of CAIX in cancer stromal cells as hypoxic marker in this study. Multivariate Cox regression analysis revealed that the presence of hypoxic foci was an independent predictor of shorter DFS (P=0.005) and DSS (P=0.011) (Supplementary Table 1). The presence of necrosis was significantly correlated with the presence of hypoxic foci (Table 1). More CAIX-expressing cells were found in larger areas of necrosis.


Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation.

Hiraoka N, Ino Y, Sekine S, Tsuda H, Shimada K, Kosuge T, Zavada J, Yoshida M, Yamada K, Koyama T, Kanai Y - Br. J. Cancer (2010)

Kaplan–Meier survival curves showing the comparison of disease-free survival between high and low expression of CAIX (P-values obtained from log-rank test) (left columns). Kaplan–Meier survival curves showing the comparison of disease-specific survival between high and low expression of CAIX (P-values obtained from log-rank test) (right columns).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965866&req=5

fig3: Kaplan–Meier survival curves showing the comparison of disease-free survival between high and low expression of CAIX (P-values obtained from log-rank test) (left columns). Kaplan–Meier survival curves showing the comparison of disease-specific survival between high and low expression of CAIX (P-values obtained from log-rank test) (right columns).
Mentions: Survival analysis showed that the presence of hypoxic foci with expression of CAIX in stromal cells in cancer tissue was closely associated with shorter DFS (P=0.004) and DSS (P=0.003) (Figure 3). The presence of cancer cells expressing CAIX was also associated with shorter survival rates (Figure 3), although its occasional expression in cancer cells forming well-differentiated glands distant from necrotic areas probably indicated a cellular phenotype similar to that of normal ductal epithelial cells, and was unrelated to hypoxia. Then we used expression of CAIX in cancer stromal cells as hypoxic marker in this study. Multivariate Cox regression analysis revealed that the presence of hypoxic foci was an independent predictor of shorter DFS (P=0.005) and DSS (P=0.011) (Supplementary Table 1). The presence of necrosis was significantly correlated with the presence of hypoxic foci (Table 1). More CAIX-expressing cells were found in larger areas of necrosis.

Bottom Line: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype.The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC.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.

View Article: PubMed Central - PubMed

Affiliation: Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. nhiraoka@ncc.go.jp

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.

Show MeSH
Related in: MedlinePlus