Tumor angiogenesis predicts recurrence with normal serum carcinoembryonic antigen in advanced rectal carcinoma patients

Abstract

Many studies have established the usefulness of serum carcinoembryonic antigen (CEA) oriented serial monitoring for predicting recurrence and prognosis; however, few studies have so far investigated serum CEA-negative recurrence. The aim of this study was to elucidate the nature of CEA-negative recurrence regarding tumor angiogenesis. Fifty-seven patients with T3/T4 rectal cancer were divided into the two groups according to the serum CEA status. Angiogenesis was defined as the intratumoral vessel count by immunohistochemical staining using CD31. The CD31 count was significantly higher in the recurrent patients in both groups and the ratio of nodal involvement was significantly higher in the recurrent patients of the CEA-negative group. Local recurrence mainly developed in the CEA-negative group; however, the CD31 count did not predict the sites of recurrence nor the relapse period in the both groups. A multivariate analysis showed a high CD31 count >26) to be a prognostic factor not only for recurrence but also for survival (P = 0.001, 0.043, respectively). These results suggest that a high degree of tumor angiogenesis in sections of T3/T4 rectal cancer may therefore be an important predictor for CEA-negative recurrence.

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

“…To better describe the patients included in our meta-analysis, we used Dukes staging whenever possible. For one study (Ishikawa et al, 1999), in the absence of lymph node involvement or metastasis, we could convert stage T 1 -3 N 0 M 0 into stage A or B.…”

“…Thirty-two independent studies representing 3496 patients with mean age of 64.7 years (1740 male patients, 1400 female patients) included 1449 colon and 673 rectum cancers. These studies included 286 stage A, 1315 stage B, 1085 stage C and 388 stage D. There were only eight series of consecutive patients (Lindmark et al, 1996;Ishikawa et al, 1999;Vermeulen et al, 1999;Pietra et al, 2000;Prall et al, 2003;Shan et al, 2003;Galizia et al, 2004;Liang et al, 2004) and one prospective study (Nanni et al, 2002), compared to 23 retrospective studies.…”

“…Finally, statistical calculations could be performed in 22 studies for MVD including nine studies (n ¼ 957) for RFS (Engel et al, 1996;Takahashi et al, 1997;Choi et al, 1998;Ishikawa et al, 1999;Nanni et al, 2002;Shan et al, 2003;Galizia et al, 2004;Liang et al, 2004) and 18 for OS (n ¼ 2383) (see Appendix E). High MVD significantly predicted poor RFS (RR ¼ 2.32; 95% CI: 1.39 -3.90; Po0.001) and poor OS (RR ¼ 1.44; 95% CI: 1.08 -1.92; P ¼ 0.01).…”

“…We also screened references from the relevant literature, including all of the identified studies, but also reviews and editorials (Papamichael, 2001;Poon et al, 2003). We wrote or e-mailed to the authors of 20 studies (see Appendix A) for additional information and, in 5 occasions obtained the data needed for the meta-analytic calculations Ishikawa et al, 1999;Harada et al, 2001;Khorana et al, 2003;Galizia et al, 2004). We tried carefully to avoid duplication of data, by examining for each publication the names of all authors and the different medical centres involved.…”

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

“…In addition, tumour vessel density is in a variety of tumours a predictive parameter for metastatic propagation and/or overall survival or relapse-free survival, e.g., in breast (Weidner et al, 1991(Weidner et al, , 1992 and prostate cancer (Weidner et al, 1993), in melanomas (Herlyn et al, 1987), colorectal carcinomas (Ishikawa et al, 1999) and oesophageal carcinomas (Kitadai et al, 1998).…”