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Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer.

Smith RA, Tang J, Tudur-Smith C, Neoptolemos JP, Ghaneh P - Br. J. Cancer (2011)

Bottom Line: Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data.There was evidence of significant heterogeneity in four of the seven study groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Royal Liverpool University Hospital, 5th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK.

ABSTRACT

Background: The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods: Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log(e) hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ(2) test for heterogeneity and its impact on the meta-analysis was assessed by the I(2) statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.

Results: Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18-1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38-0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48-0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43-0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups.

Conclusion: These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.

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Related in: MedlinePlus

Forrest plot to assess overall effect of p53, smad4 and EGFR expression on survival.
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fig2: Forrest plot to assess overall effect of p53, smad4 and EGFR expression on survival.

Mentions: The 11 eligible studies (all retrospective) included a total of 767 patients with a median number of 62 patients per study (range=19–142). Table 2 outlines the demographic, clinico-pathological, methodological and outcome characteristics of these studies. The median quality score was recorded as 70% (range=60–95%). There was no significant difference in median quality scores between significant and non-significant studies (Mann–Whitney, P=0.516). Similarly, there was no significant correlation between study size and quality scores (Spearman's ρ=0.139, P=0.698). Figure 1 illustrates the Forrest plot for the survival data. Significant heterogeneity was demonstrated according to Cochran's χ2 test (χ2=22.08, P=0.01; I2=54.7%). The combined HR was recorded as 1.51 (95% CI=1.18–1.92), indicating that positive immunostaining for VEGF was significantly associated with adverse survival in the pooled patient group. When assessing the funnel plot for this analysis (Figure 2), the data points approximated a symmetrical distribution (Egger's test, P=0.269), indicating that publication bias is unlikely to be a significant confounding factor in describing this relationship.


Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer.

Smith RA, Tang J, Tudur-Smith C, Neoptolemos JP, Ghaneh P - Br. J. Cancer (2011)

Forrest plot to assess overall effect of p53, smad4 and EGFR expression on survival.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101928&req=5

fig2: Forrest plot to assess overall effect of p53, smad4 and EGFR expression on survival.
Mentions: The 11 eligible studies (all retrospective) included a total of 767 patients with a median number of 62 patients per study (range=19–142). Table 2 outlines the demographic, clinico-pathological, methodological and outcome characteristics of these studies. The median quality score was recorded as 70% (range=60–95%). There was no significant difference in median quality scores between significant and non-significant studies (Mann–Whitney, P=0.516). Similarly, there was no significant correlation between study size and quality scores (Spearman's ρ=0.139, P=0.698). Figure 1 illustrates the Forrest plot for the survival data. Significant heterogeneity was demonstrated according to Cochran's χ2 test (χ2=22.08, P=0.01; I2=54.7%). The combined HR was recorded as 1.51 (95% CI=1.18–1.92), indicating that positive immunostaining for VEGF was significantly associated with adverse survival in the pooled patient group. When assessing the funnel plot for this analysis (Figure 2), the data points approximated a symmetrical distribution (Egger's test, P=0.269), indicating that publication bias is unlikely to be a significant confounding factor in describing this relationship.

Bottom Line: Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data.There was evidence of significant heterogeneity in four of the seven study groups.

View Article: PubMed Central - PubMed

Affiliation: Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Royal Liverpool University Hospital, 5th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK.

ABSTRACT

Background: The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods: Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log(e) hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ(2) test for heterogeneity and its impact on the meta-analysis was assessed by the I(2) statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.

Results: Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18-1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38-0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48-0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43-0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups.

Conclusion: These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.

Show MeSH
Related in: MedlinePlus