The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery.
The goal of targeted therapy has driven a search for markers of prognosis and response to adjuvant therapy. The surgical resection of a solid tumour induces tissue ischaemia and acidosis, both potent mediators of gene expression. This study investigated the impact of colorectal cancer (CRC) surgery on prognostic and predictive marker levels. Tumour expression of thymidylate synthase, thymidine phosphorylase, cyclin A, vascular endothelial growth factor (VEGF), carbonic anhydrase-9, hypoxia inducible factor-1alpha, and glucose transporter-1 (GLUT-1) proteins was determined before and after rectal cancer surgery. Spectral imaging of tissue sections stained by immunohistochemistry provided quantitative data. Surgery altered thymidylate synthase protein expression (P=0.02), and this correlated with the change in the proliferation marker cyclin A. The expression of hypoxia inducible factor-1alpha, VEGF, and GLUT-1 proteins was also different following surgery. Colorectal cancer surgery significantly impacts on intratumoral gene expression, suggesting archival specimens may not accurately reflect in situ marker levels. Although rectal cancer was the studied model, the results may be applicable to any solid tumour undergoing extirpation in which molecular markers have been proposed to guide patient therapy.
Atkin
G K
GK
Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK, and Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201-2013, USA. gkatkin@blueyonder.co.uk
Daley
F M
FM
Bourne
S
S
Glynne-Jones
R
R
Northover
J M A
JM
Wilson
G D
GD
D000230:Adenocarcinoma / Q000378:metabolism / Q000601:surgery*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D013505:Digestive System Surgical Procedures / Q000009:adverse effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012004:Rectal Neoplasms / Q000378:metabolism / Q000601:surgery*; D012007:Rectum / Q000098:blood supply; D013940:Thymidylate Synthase / Q000378:metabolism
D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase