Limits...
COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis.

Pomianowska E, Schjølberg AR, Clausen OP, Gladhaug IP - BMC Cancer (2014)

Bottom Line: In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival.In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002).In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. ewa.pomianowska@medisin.uio.no.

ABSTRACT

Background: Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas.

Methods: The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed.

Results: COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model.

Conclusions: COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis.

Show MeSH

Related in: MedlinePlus

Overall survival analysis stratified by COX-2 expression. a Ampullary cancer (AC), b Distal bile duct cancer (DBC), c Pancreatic cancer (PC). d-f Overall survival analysis for AC, DBC and PC with pancreatobiliary differentiation stratified by COX-2 expression. g-i Overall survival analysis for AC, DBC and PC with intestinal differentiation stratified by COX-2 expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4230243&req=5

Figure 2: Overall survival analysis stratified by COX-2 expression. a Ampullary cancer (AC), b Distal bile duct cancer (DBC), c Pancreatic cancer (PC). d-f Overall survival analysis for AC, DBC and PC with pancreatobiliary differentiation stratified by COX-2 expression. g-i Overall survival analysis for AC, DBC and PC with intestinal differentiation stratified by COX-2 expression.

Mentions: COX-2 staining was very similar in all three tumour types, with a positivity rate of 71% in PC, 72% in DBC, and 77% in AC. The COX-2 expression was detected in the cytoplasm of cancer cells in all three types of adenocarcinoma. No COX-2 immunostaining was detected in the stroma cells (Figure 1a,b, and e). The expression pattern showed heterogeneity both among different tumours and within the individual tumour, as areas with moderate to strong staining coexisted with negative areas within the same tumour (Figure 1c). Islet cells expressed moderately to strong COX-2 staining in all cases including those with no COX-2 expression in the tumour (Figure 1d). Irrespective of tumour origin, overall patient survival was more favourable in COX-2 positive than COX-2 negative tumours (Figure 2a-c). This was particularly prominent in AC (p = 0.011) and PC (p = 0.043) whereas the same tendency was seen in DBC although not reaching significance (p = 0.06). COX-2 expression varied according to the type of histological differentiation. In tumours with pancreatobiliary type of differentiation, two thirds of the tumours were COX-2 positive irrespective of anatomical origin (67%, 69%, and 68% in AC, DBC and PC, respectively). However there was no significant difference in overall survival when comparing COX-2 positive and negative tumours in this group (Figure 2d-f). All PC and DBC tumours with intestinal type of differentiation were COX-2 positive whereas 84% of the intestinal AC tumours expressed COX-2. The survival data of the intestinal AC tumours showed a favourable prognosis for patients with tumours expressing COX-2 (p = 0.003) (Figure 2g-i).


COX-2 overexpression in resected pancreatic head adenocarcinomas correlates with favourable prognosis.

Pomianowska E, Schjølberg AR, Clausen OP, Gladhaug IP - BMC Cancer (2014)

Overall survival analysis stratified by COX-2 expression. a Ampullary cancer (AC), b Distal bile duct cancer (DBC), c Pancreatic cancer (PC). d-f Overall survival analysis for AC, DBC and PC with pancreatobiliary differentiation stratified by COX-2 expression. g-i Overall survival analysis for AC, DBC and PC with intestinal differentiation stratified by COX-2 expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230243&req=5

Figure 2: Overall survival analysis stratified by COX-2 expression. a Ampullary cancer (AC), b Distal bile duct cancer (DBC), c Pancreatic cancer (PC). d-f Overall survival analysis for AC, DBC and PC with pancreatobiliary differentiation stratified by COX-2 expression. g-i Overall survival analysis for AC, DBC and PC with intestinal differentiation stratified by COX-2 expression.
Mentions: COX-2 staining was very similar in all three tumour types, with a positivity rate of 71% in PC, 72% in DBC, and 77% in AC. The COX-2 expression was detected in the cytoplasm of cancer cells in all three types of adenocarcinoma. No COX-2 immunostaining was detected in the stroma cells (Figure 1a,b, and e). The expression pattern showed heterogeneity both among different tumours and within the individual tumour, as areas with moderate to strong staining coexisted with negative areas within the same tumour (Figure 1c). Islet cells expressed moderately to strong COX-2 staining in all cases including those with no COX-2 expression in the tumour (Figure 1d). Irrespective of tumour origin, overall patient survival was more favourable in COX-2 positive than COX-2 negative tumours (Figure 2a-c). This was particularly prominent in AC (p = 0.011) and PC (p = 0.043) whereas the same tendency was seen in DBC although not reaching significance (p = 0.06). COX-2 expression varied according to the type of histological differentiation. In tumours with pancreatobiliary type of differentiation, two thirds of the tumours were COX-2 positive irrespective of anatomical origin (67%, 69%, and 68% in AC, DBC and PC, respectively). However there was no significant difference in overall survival when comparing COX-2 positive and negative tumours in this group (Figure 2d-f). All PC and DBC tumours with intestinal type of differentiation were COX-2 positive whereas 84% of the intestinal AC tumours expressed COX-2. The survival data of the intestinal AC tumours showed a favourable prognosis for patients with tumours expressing COX-2 (p = 0.003) (Figure 2g-i).

Bottom Line: In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival.In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002).In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. ewa.pomianowska@medisin.uio.no.

ABSTRACT

Background: Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas.

Methods: The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed.

Results: COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model.

Conclusions: COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis.

Show MeSH
Related in: MedlinePlus