Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma

Matthews, Leo H. McCormick; Noble, Fergus; Tod, Jo; Jaynes, Eleanor; Harris, Scott; Primrose, John; Ottensmeier, Christian; Thomas, Gareth J.; Underwood, Tim

doi:10.1038/bjc.2015.179

Cited by 35 publications

(18 citation statements)

References 116 publications

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“…A higher expression of P53, HER2, and GLUT1 has individually been shown to be associated with a worse survival in esophageal adenocarcinoma [19]. However, there have been a variety of other cancers which have been investigated with a similar methodology.…”

Section: Introductionmentioning

confidence: 99%

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

McCain¹,

McManus

McQuaid³

et al. 2019

Cancer Causes Control

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Purpose To investigate the association between cigarette smoking, alcohol consumption, and esophageal adenocarcinoma survival, including stratified analysis by selected prognostic biomarkers. Methods A population-representative sample of 130 esophageal adenocarcinoma patients (n = 130) treated at the Northern Ireland Cancer Centre between 2004 and 2012. Cox proportional hazards models were applied to evaluate associations between smoking status, alcohol intake, and survival. Secondary analyses investigated these associations across categories of p53, HER2, CD8, and GLUT-1 biomarker expression. Results In esophageal adenocarcinoma patients, there was a significantly increased risk of cancer-specific mortality in ever, compared to never, alcohol drinkers in unadjusted (HR 1.96 95% CI 1.13-3.38) but not adjusted (HR 1.70 95% CI 0.95-3.04) analysis. This increased risk of death observed for alcohol consumers was more evident in patients with normal p53 expression, GLUT-1 positive or CD-8 positive tumors. There were no significant associations between survival and smoking status in esophageal adenocarcinoma patients. Conclusions In esophageal adenocarcinoma patients, cigarette smoking or alcohol consumption was not associated with a significant difference in survival in comparison with never smokers and never drinkers in fully adjusted analysis. However, in some biomarker-selected subgroups, ever-alcohol consumption was associated with a worsened survival in comparison with never drinkers. Larger studies are needed to investigate these findings, as these lifestyle habits may not only be linked to cancer risk but also cancer survival.

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Section: Introductionmentioning

confidence: 99%

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

McCain¹,

McManus

McQuaid³

et al. 2019

Cancer Causes Control

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“…The fraction of Ki67‐positive tumor cells (Ki67 labeling index, Ki LI) has been proven to be an established prognostic marker for various tumor types, especially in breast cancer (Hu et al ., ; Li et al ., ). Previous studies have shown a strong linear correlation between Ki‐67 labeling index and esophageal adenocarcinoma development (McCormick Matthews et al ., ). However, the prognostic significance of Ki67 expression in ESCC remains inconclusive.…”

Section: Discussionmentioning

confidence: 97%

Prognostic value of an immunohistochemical signature in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy

Zhang

Xiu

et al. 2018

Molecular Oncology

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Here, we aimed to identify an immunohistochemical (IHC)‐based classifier as a prognostic factor in patients with esophageal squamous cell carcinoma (ESCC). A cohort of 235 patients with ESCC undergoing radical esophagectomy (with complete clinical and pathological information) were enrolled in the study. Using the least absolute shrinkage and selection operator (LASSO) regression model, we extracted six IHC features associated with progression‐free survival (PFS) and then built a classifier in the discovery cohort (n = 141). The prognostic value of this classifier was further confirmed in the validation cohort (n = 94). Additionally, we developed a nomogram integrating the IHC‐based classifier to predict the PFS. We used the IHC‐based classifier to stratify patients into high‐ and low‐risk groups. In the discovery cohort, 5‐year PFS was 22.4% (95% CI: 0.14–0.36) for the high‐risk group and 43.3% (95% CI: 0.32–0.58) for the low‐risk group (P = 0.00064), and in the validation cohort, 5‐year PFS was 20.58% (95% CI: 0.12–0.36) for the high‐risk group and 36.43% (95% CI: 0.22–0.60) for the low‐risk group (P = 0.0082). Multivariable analysis demonstrated that the IHC‐based classifier was an independent prognostic factor for predicting PFS of patients with ESCC. We further developed a nomogram integrating the IHC‐based classifier and clinicopathological risk factors (gender, American Joint Committee on Cancer staging, and vascular invasion status) to predict the 3‐ and 5‐year PFS. The performance of the nomogram was evaluated and proved to be clinically useful. Our 6‐IHC marker‐based classifier is a reliable prognostic tool to facilitate the individual management of patients with ESCC after radical esophagectomy.

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“…Previous studies that attempted to identify clinically applicable predictive biomarkers for treatment response or overall prognosis have often been underpowered or included heterogeneous patient populations with squamous cell carcinoma and adenocarcinoma. Biomarker analysis can also be hampered by different neoadjuvant treatments in advanced OAC, making comparisons between studies difficult.…”

Section: Discussionmentioning

confidence: 99%

Loss of SRY-box2 (SOX2) expression and its impact on survival of patients with oesophageal adenocarcinoma

Kate

Olphen

Bruno

et al. 2017

British Journal of Surgery

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BackgroundOesophageal adenocarcinoma (OAC) is a highly aggressive malignancy with poor survival, which is highly variable amongst patients with comparable conventional prognosticators. Therefore molecular biomarkers are urgently needed to improve the prediction of survival in these patients. SRY (sex determining region Y)‐box 2, also known as SOX2, is a transcription factor involved in embryonal development of the gastrointestinal tract as well as in carcinogenesis. The purpose of this study was to see whether SOX2 expression is associated with survival in patients with OAC.Methods SOX2 was studied by immunohistochemistry in patients who had undergone potentially curative oesophagectomy for adenocarcinoma. Protein expression of SOX2 was evaluated using tissue microarrays from resection specimens, and results were analysed in relation to the clinical data by Cox regression analysis. SOX2 was evaluated in two independent OAC cohorts (Rotterdam cohort and a multicentre UK cohort).ResultsLoss of SOX2 expression was independently predictive of adverse overall survival in the multivariable analysis, adjusted for known factors influencing survival, in both cohorts (Rotterdam cohort: hazard ratio (HR) 1·42, 95 per cent c.i. 1·07 to 1·89, P = 0·016; UK cohort: HR 1·54, 1·08 to 2·19, P = 0·017). When combined with clinicopathological staging, loss of SOX2 showed an increased effect in patients with pT1–2 tumours (P = 0·010) and node‐negative OAC (P = 0·038), with an incrementally adverse effect on overall survival for stage I OAC with SOX2 loss (HR 3·18, 1·18 to 8·56; P = 0·022).Conclusion SOX2 is an independent prognostic factor for long‐term survival in OAC, especially in patients with stage I OAC.

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Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma

Cited by 35 publications

References 116 publications

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

Alcohol intake, tobacco smoking, and esophageal adenocarcinoma survival: a molecular pathology epidemiology cohort study

Prognostic value of an immunohistochemical signature in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy

Loss of SRY-box2 (SOX2) expression and its impact on survival of patients with oesophageal adenocarcinoma

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