C-reactive protein is associated with distant metastasis of T3 colorectal cancer.

Few studies have examined the relationship between systemic inflammatory response (SIR) and distant metastasis in patients with T3 colorectal cancer (T3 CRC). Uni- and multivariate analyses were performed in order to evaluate the influence of SIR on distant metastasis in patients with T3 CRC using collected clinical data. Between January 2000 and August 2009, 335 patients with pathologically diagnosed T3CRC were enrolled. Univariate analysis revealed that tumor differentiation, lymphatic invasion, venous invasion, lymph node metastasis, serum carcinoembryonic antigen (CEA) level, carbohydrate antigen 19-9 (CA 19-9) level, C-reactive protein (CRP) level and the Glasgow Prognostic Score (GPS) were associated with distant metastasis. Multivariate analysis using these selected characteristics disclosed that the CRP level was associated with distant metastasis of T3 CRC, as well as with lymph node metastasis, and CEA and CA19-9 levels. The level of CRP is one of the important clinical characteristics associated with distant metastasis of T3 CRC. A preliminary study conducted by our group (1) has demonstrated that the systemic inflammatory response (SIR) (2) including the Glasgow Prognostic Score (GPS) (3, 4), which reflects the levels of C-reactive protein (CRP) and albumin in serum, is associated with distant metastasis in patients with T1 or T2 colorectal cancer (CRC) (1). However, since only four patients with distant metastasis were included, the significance of the relationship between SIR and distant metastasis remained statistically unproven in that setting. Therefore, we considered that it would be valuable to examine the relationship between SIR and distant metastasis in the setting of T3 CRC, as T3 CRC is considered to be an ideal study model for this purpose in three respects. Firstly, because T3 CRC is diagnosed on the basis not only of infiltration to the serosa or subserosa, but also the lack of direct infiltration to other organs, it is theoretically resectable, as well as T1 or T2 CRC. Secondly, because T3 CRC infiltrates more deeply than T1 or T2 CRC, the former is well known to have a much higher rate of distant metastasis than the latter two. Thirdly, since T3 CRC has three independent stages, it is acceptable to hypothesize that patients with T3 CRC with distant metastasis (stage IV) would have a greater degree of hypercytokinemia (5), which is thought to induce SIR, than patients without distant metastasis (stage III) or lymph node metastasis (stage II). In fact, recent studies have shown that evaluation of SIR, and especially the GPS (3), is more useful for predicting postoperative survival in patients with advanced cancer than in those with early-phase cancer (6-8). Moreover, several studies have demonstrated that there is a close relationship between SIR (9-11) and surgical outcome in patients with CRC. In order to strengthen the evidence obtained in our previous study (1), the present investigation was conducted in a similar manner in order to evaluate the relationship between SIR and distant metastasis of T3 CRC using the clinical characteristics of the patients.