SCIENCE REVIEW
Oesophagogastric cancer and VEGF: an update
Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that regulates tumour angiogenesis. The prognostic significance of VEGF expression remains incompletely investigated for patients with oesophagogastric cancer, and therefore a study undertaken by workers in Northern Ireland (Gray RT, O’Donnell ME, McGuigan JA, Spence GM. Quantification of tumour and circulating vascular endothelial growth factor [VEGF] in patients with oesophagogastric cancer: a long-term follow-up study. Br J Biomed Sci 2012; 69 [2]: 71–5) assessed the significance of tumour VEGF (T-VEGF) and circulating VEGF (C-VEGF) expression in a 10-year follow-up of patients with oesophagogastric cancer. In the study, patients undergoing surgical resection were prospectively recruited and circulating VEGF, derived both from plasma (P-VEGF) and serum (S-VEGF), and T-VEGF were assessed using a commercial enzyme- linked immunosorbent assay (ELISA). As platelet count may contribute to C-VEGF,
There is a compelling body of evidence linking tumour growth, metastasis and poor outcome with tumour angiogenesis in many solid malignancies. Vascular endothelial growth factor (VEGF) is a pro-angiogenic cytokine that is important in tumour angiogenesis. Tumour VEGF (T-VEGF) is over-expressed in 30–60% of patients with oesophageal carcinoma. In patients with squamous cell carcinoma it correlates with lymph node metastasis and outcome. However, T-VEGF expression does not appear to correlate with aggressive tumour characteristics or patient outcome in oesophageal adenocarcinoma, although it does correlate with the transition from Barrett’s oesophagus to high-grade
696 THE BIOMEDICAL SCIENTIST
pre-operative platelet levels were also recorded to exclude a confounding effect. Although a trend towards decreased survival was observed for patients who had positive lymph nodes, ELISA quantification of circulatory or T-VEGF did not appear to be a significant predictor of mortality in patients with oesophagogastric cancer. In a more recent study, a group in Osaka, Japan, looked at predictors of nodal involvement in oesophageal squamous cell carcinoma (Nakagawa Y, Ohira M, Kubo N et al. Tumour budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma. Anticancer Res 2013; 33 [11]: 5023–9). It showed significant correlation between immunohistochemical staining of C-VEGF and E-cadherin in the primary tumour and tumour budding for prediction of nodal metastasis, but found that neither correlated with poor survival.
dysplasia, and with the transition from carcinoma in situ to locally advanced disease. Measurement of VEGF levels within the systemic circulation (C-VEGF) has been identified as a useful predictor of survival in other solid organ malignancies, such as colorectal and small cell lung carcinoma. The prognostic significance of C-VEGF in oesophagogastric cancer remains unclear. Circulating VEGF has been assayed predominantly in serum, but some authors have previously implicated ex vivo platelet activation as a potential source of elevated VEGF. Consequently, plasma VEGF (P-VEGF) may be a more accurate marker of circulating VEGF in vivo.
‘Vascular endothelial growth factor is a pro-angiogenic cytokine that is important in tumour angiogenesis’
Previously, the relationship between
T-VEGF and C-VEGF has been investigated as a potential marker of angiogenesis and the presence of bone marrow micrometastases, a surrogate marker of tumour cell dissemination, in patients with oesophagogastric cancer. Plasma VEGF correlated with the detection of micrometastatic cells in bone marrow, but T-VEGF did not. The significance of bone marrow micrometastases as a marker of tumour cell dissemination and adverse prognosis in oesophagogastric cancer remains unproven.
NORTHERN IRELAND STUDY A study undertaken by workers in Northern Ireland (Gray RT, O’Donnell ME, McGuigan JA, Spence GM. Quantification of tumour and circulating vascular endothelial growth factor [VEGF] in patients with oesophagogastric cancer: a long-term follow-up study. Br J Biomed Sci 2012; 69 [2]: 71–5) aimed to assess the direct prognostic significance of P-VEGF, S-VEGF and T-VEGF in patients with oesophagogastric cancer. The prognostic significance of pre-operative platelet count was also assessed as platelets are a potential source of VEGF in the circulation. Patients in the study were followed up over a 10-year period using the Northern Ireland Cancer Registry. Sixty-one patients were recruited (men=45) with a mean age of 65.7 years. The 10-year survival was 19.7% (n=12) with a median follow-up of 808 days (interquartile range [IQR]: 349.5–2358.5). Union for International Cancer Control (UICC) tumour staging was Stage I=9 (14.8%), Stage II=15 (24.6%), Stage III=33 (54.1%) and Stage IV=4 (6.6%). The only significant relationship between
DECEMBER 2013
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