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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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Representative histology of massive necrosis (upper columns) and micronecrosis (lower columns). Arrows indicate necrotic area. Left, centre, and right columns are in low ( × 6.25), middle ( × 20), and high magnification ( × 100), respectively. High power view of histology in right columns corresponds to the rectangle (solid line) in left or middle column. Middle power view of histology in centre columns corresponds to the rectangle (dotted line) in left columns.
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fig1: Representative histology of massive necrosis (upper columns) and micronecrosis (lower columns). Arrows indicate necrotic area. Left, centre, and right columns are in low ( × 6.25), middle ( × 20), and high magnification ( × 100), respectively. High power view of histology in right columns corresponds to the rectangle (solid line) in left or middle column. Middle power view of histology in centre columns corresponds to the rectangle (dotted line) in left columns.

Mentions: Tumour necrosis in PDCs was reported previously (Couvelard et al, 2005; Mitsunaga et al, 2005), having been defined as ‘confluent cell death in invasive areas of primary cancer, visible at an objective lens magnification of × 4′ (Mitsunaga et al, 2005), which is the same to the definition having been mentioned in breast cancer. Tumour histology often varies among the organs in which tumours develop. We noticed that small areas of necrosis were evident in PDCs, wherein gland formation by cancer cells was ruptured, usually in association with neutrophil infiltration. We refer to this hereafter as micronecrosis, and to the former as massive necrosis. As sometimes it is difficult to differentiate necrotic lesions into either of these two patterns, we combined these two types of lesions solely as ‘necrosis'. The definition of histological necrosis is as follows. Necrosis occurs in cancer tissue regardless of its extent, and is usually found in both cancer cells and cancer stroma (Figure 1). When coagulation necrosis is extensively developed (massive necrosis), it corresponds to what was referred to as necrosis previously (Couvelard et al, 2005; Mitsunaga et al, 2005). Smaller areas of necrosis (micronecrosis) often recognised adjacent to ruptured cancer-forming tubules is almost always accompanied by neutrophil infiltration (Figure 1).


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)

Representative histology of massive necrosis (upper columns) and micronecrosis (lower columns). Arrows indicate necrotic area. Left, centre, and right columns are in low ( × 6.25), middle ( × 20), and high magnification ( × 100), respectively. High power view of histology in right columns corresponds to the rectangle (solid line) in left or middle column. Middle power view of histology in centre columns corresponds to the rectangle (dotted line) in left columns.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Representative histology of massive necrosis (upper columns) and micronecrosis (lower columns). Arrows indicate necrotic area. Left, centre, and right columns are in low ( × 6.25), middle ( × 20), and high magnification ( × 100), respectively. High power view of histology in right columns corresponds to the rectangle (solid line) in left or middle column. Middle power view of histology in centre columns corresponds to the rectangle (dotted line) in left columns.
Mentions: Tumour necrosis in PDCs was reported previously (Couvelard et al, 2005; Mitsunaga et al, 2005), having been defined as ‘confluent cell death in invasive areas of primary cancer, visible at an objective lens magnification of × 4′ (Mitsunaga et al, 2005), which is the same to the definition having been mentioned in breast cancer. Tumour histology often varies among the organs in which tumours develop. We noticed that small areas of necrosis were evident in PDCs, wherein gland formation by cancer cells was ruptured, usually in association with neutrophil infiltration. We refer to this hereafter as micronecrosis, and to the former as massive necrosis. As sometimes it is difficult to differentiate necrotic lesions into either of these two patterns, we combined these two types of lesions solely as ‘necrosis'. The definition of histological necrosis is as follows. Necrosis occurs in cancer tissue regardless of its extent, and is usually found in both cancer cells and cancer stroma (Figure 1). When coagulation necrosis is extensively developed (massive necrosis), it corresponds to what was referred to as necrosis previously (Couvelard et al, 2005; Mitsunaga et al, 2005). Smaller areas of necrosis (micronecrosis) often recognised adjacent to ruptured cancer-forming tubules is almost always accompanied by neutrophil infiltration (Figure 1).

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