In the Journals

Tumor protein 53 adversely affects survival rates in esophageal cancer

Overall survival rates were found to be reduced in patients with esophageal adenocarcinoma who also had the gene mutation tumor protein 53, or TP53, compared with patients with esophageal adenocarcinoma who did not have TP53 as a biomarker. Furthermore, the association existed in patients independent of tumor stage.

Oliver M. Fisher, MD, of the gastroesophageal cancer program, St. Vincent’s Centre for Applied Medical Research University of New South Wales, Sydney, and colleagues discussed the rapidly growing incidence of esophageal adenocarcinoma and the need for biomarkers to help clinicians manage these patients with esophageal adenocarcinoma. 

“The incidence of [esophageal adenocarcinoma] has increased faster than any other cancer since the 1970s in many Western countries with highest incidence rates found in Northern and Western Europe, Northern America and Oceania, with a greater than sixfold increase during the past 3 decades,” the researchers wrote. 

In this study, Fisher and colleagues conducted a systematic review of prospective or retrospective clinical studies found by searching Medline, Embase, PubMed and Current Contents. The studies that were included measured TP53 status and had sufficient data to calculate HRs or the estimation of HR for survival in patients with esophageal adenocarcinoma and TP53 or a subgroup of patients with esophageal adenocarcinoma alone. In 16 studies, 888 patients were identified and assigned to subgroups of either having TP53 mutation status or not having the mutation status for comparison. The studies used in the review were all published between 1990 and February 2015.

The researchers found that TP53 mutations in patients with esophageal adenocarcinoma were associated with reduced survival (HR = 1.48; 95% CI, 1.16-1.9). 

There were 14 studies that recorded survival time data for the subgroup of patients with TP53. Researchers calculated that the median survival time for these patients was 18.9 months (n = 488) compared with 26.2 months for patients who did not have the TP53 mutation status (n = 423). 

Also, the researchers recorded a greater prognostic effect (HR = 2.11; 95% CI, 1.35-3.31) in a sensitivity analysis of studies assessed at a low risk of bias that only reported survival for patients with esophageal adenocarcinoma alone.

“This study indicates that mutated TP53 negatively impacts overall survival in patients with [esophageal adenocarcinoma], independent of tumor stage. This effect is estimated as a relative increase in hazard of death of 48%, with up to a 211% increase when studies of mixed histology cohorts or high risk of bias are excluded. This corresponds to a reduced survival time of approximately 7 months based on median survival from the included studies. This effect size is similar to the difference in median survival of stage IIIA compared with stage IIIC [esophageal adenocarcinoma]. To our knowledge, this is the first comprehensive systematic review and meta-analysis of the prognostic impact of TP53 mutations in patients with [esophageal adenocarcinoma] that includes an assessment independent of tumor stage,” the researchers wrote.

Disclosure: Fisher is supported by the Swiss Cancer League (BIL-KLS 133-02-2013), the Australian National Health & Medical Research Council (GNT1094423) and the Swiss National Science Foundation (P1SKP3_161806). Another researcher was supported by the Swedish Society of Medicine, the Maggie Stephens Foundation and the Sparre Foundation.

Overall survival rates were found to be reduced in patients with esophageal adenocarcinoma who also had the gene mutation tumor protein 53, or TP53, compared with patients with esophageal adenocarcinoma who did not have TP53 as a biomarker. Furthermore, the association existed in patients independent of tumor stage.

Oliver M. Fisher, MD, of the gastroesophageal cancer program, St. Vincent’s Centre for Applied Medical Research University of New South Wales, Sydney, and colleagues discussed the rapidly growing incidence of esophageal adenocarcinoma and the need for biomarkers to help clinicians manage these patients with esophageal adenocarcinoma. 

“The incidence of [esophageal adenocarcinoma] has increased faster than any other cancer since the 1970s in many Western countries with highest incidence rates found in Northern and Western Europe, Northern America and Oceania, with a greater than sixfold increase during the past 3 decades,” the researchers wrote. 

In this study, Fisher and colleagues conducted a systematic review of prospective or retrospective clinical studies found by searching Medline, Embase, PubMed and Current Contents. The studies that were included measured TP53 status and had sufficient data to calculate HRs or the estimation of HR for survival in patients with esophageal adenocarcinoma and TP53 or a subgroup of patients with esophageal adenocarcinoma alone. In 16 studies, 888 patients were identified and assigned to subgroups of either having TP53 mutation status or not having the mutation status for comparison. The studies used in the review were all published between 1990 and February 2015.

The researchers found that TP53 mutations in patients with esophageal adenocarcinoma were associated with reduced survival (HR = 1.48; 95% CI, 1.16-1.9). 

There were 14 studies that recorded survival time data for the subgroup of patients with TP53. Researchers calculated that the median survival time for these patients was 18.9 months (n = 488) compared with 26.2 months for patients who did not have the TP53 mutation status (n = 423). 

Also, the researchers recorded a greater prognostic effect (HR = 2.11; 95% CI, 1.35-3.31) in a sensitivity analysis of studies assessed at a low risk of bias that only reported survival for patients with esophageal adenocarcinoma alone.

“This study indicates that mutated TP53 negatively impacts overall survival in patients with [esophageal adenocarcinoma], independent of tumor stage. This effect is estimated as a relative increase in hazard of death of 48%, with up to a 211% increase when studies of mixed histology cohorts or high risk of bias are excluded. This corresponds to a reduced survival time of approximately 7 months based on median survival from the included studies. This effect size is similar to the difference in median survival of stage IIIA compared with stage IIIC [esophageal adenocarcinoma]. To our knowledge, this is the first comprehensive systematic review and meta-analysis of the prognostic impact of TP53 mutations in patients with [esophageal adenocarcinoma] that includes an assessment independent of tumor stage,” the researchers wrote.

Disclosure: Fisher is supported by the Swiss Cancer League (BIL-KLS 133-02-2013), the Australian National Health & Medical Research Council (GNT1094423) and the Swiss National Science Foundation (P1SKP3_161806). Another researcher was supported by the Swedish Society of Medicine, the Maggie Stephens Foundation and the Sparre Foundation.