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. 2010 May 25;102(11):1600-7.
doi: 10.1038/sj.bjc.6605686. Epub 2010 May 11.

Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy

K R Fareed  1 , A Al-Attar, I N Soomro, P V Kaye, J Patel, D N Lobo, S L Parsons, S Madhusudan
Affiliations

Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy

K R Fareed et al. Br J Cancer. .

Abstract

Aims: Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro-oesophageal adenocarcinoma. Previously, we validated the utility of the tumour regression grade (TRG) as a histopathological marker of tumour downstaging in patients receiving platinum-based neoadjuvant chemotherapy. In this study we profiled key DNA repair and damage signalling factors and correlated them with clinicopathological outcomes, including TRG response.

Methods and results: Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays (TMAs). The first set consisted of 142 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 103 gastric/gastro-oesophageal cancer cases exposed to preoperative platinum-based chemotherapy. Expressions of ERCC1, XPF, FANCD2, APE1 and p53 were investigated using immunohistochemistry. In patients who received neoadjuvant chemotherapy, favourable TRG response (TRG 1, 2 or 3) was associated with improvement in disease-specific survival (P=0.038). ERCC1 nuclear expression correlated with lack of histopathological response (TRG 4 or 5) to neoadjuvant chemotherapy (P=0.006) and was associated with poor disease-specific (P=0.020) and overall survival (P=0.040).

Conclusions: We provide evidence that tumour regression and ERCC1 nuclear protein expression evaluated by immunohistochemistry are promising predictive markers in gastro-oesophageal cancer patients receiving neoadjuvant platinum-based chemotherapy.

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Figures

Figure 1
Figure 1
Kaplan–Meier curves representing the relationship between tumour regression grade (TRG) and disease-specific and overall survival in months from time of diagnosis in patients having received neoadjuvant chemotherapy.
Figure 2
Figure 2
Kaplan–Meier curves representing the relationship between tumour regression grade (TRG) and disease-specific and overall survival in months from time of diagnosis in patients who received surgery only.
Figure 3
Figure 3
Microphotographs of ERCC1 (strongly positive), APE1 (strongly positive) and p53 (>50% nuclei staining) immunohistochemical staining showing nuclear expression in tissue microarray cores (magnification × 100).
Figure 4
Figure 4
Kaplan–Meier curves representing the relationship between ERCC1 nuclear expression and disease-specific and overall survival in months from the time of diagnosis in the neoadjuvant group (n=57 patients).
Figure 5
Figure 5
Kaplan–Meier curves representing the relationship between APE1 expression and disease-specific survival in the neoadjuvant group (n=46 patients).
Figure 6
Figure 6
Kaplan–Meier curves representing the relationship between p53 nuclear expression and disease-specific survival in the primary surgery group.
See this image and copyright information in PMC

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