This study explored the relationships of serum
insulin-like growth factors,
IGF-I and
IGF-II, and their
binding proteins (IGFBP)-2 and
IGFBP-3, with key clinicopathological parameters in 92 patients with
colorectal cancer (cases). Comparisons were made with 57 individuals who had a normal colonoscopy (controls). Serial changes were examined in 27 cases. As IGF-related
peptides are age- and sex-dependent, absolute concentrations were converted to standard deviation scores (SDS). Mean
IGF-II SDS were elevated in Dukes A (n = 12, P< 0.001) and Dukes B (n = 25, P< 0.001) cases compared with controls, but not in advanced disease. Compared with controls, mean
IGFBP-2 SDS were significantly elevated in patients with Dukes B (P< 0.001), Dukes C (n = 13, P< 0.001) and advanced disease (n = 42, P< 0.0001), with a significant trend from early to advanced disease (one-way ANOVA, P< 0.001). Furthermore,
IGFBP-2 SDS were positively related to tumour size (P = 0.01) and fell significantly in patients following curative resection (P = 0.04), suggesting that circulating levels reflect tumour load. We tested the potential tumour marker characteristics of
IGFBP-2 SDS against three endpoints:
metastasis alone; local pelvic recurrence alone; and
metastasis and recurrence combined. The sensitivities for
IGFBP-2 alone (>/= + 2SD) were modest at 55%, 46%, and 52%, but in combination with CEA, increased substantially to 90%, 77% and 86%, respectively. We conclude that the serum
IGF-II and
IGFBP-2 profiles may provide insights into underlying
biological mechanisms, and that serum
IGFBP-2 may have an adjunct role in
cancer surveillance in patients with
colorectal cancer.