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Douglas M. Iddings, DO; Emi A. Koda, MS; Sandeep S. Grewal, MD; Ricardo Parker, PhD; Sukamal Saha, MD; Anton Bilchik, MD, PhD

Arch Surg. 2007;142:738-745.

Hypothesis  We hypothesized that p53 mutations (mp53) are associated with decreased expression of thrombospondin 1 (TSP-1) and that decreased TSP-1 expression is associated with lymph node metastases.

Design  A retrospective study of lymphatic mapping and pathologic determination of angiogenesis markers in primary colorectal cancer.

Setting  Tertiary care cancer institute.

Patients  Sixty-one patients with colorectal cancer underwent lymphatic mapping. Lymph nodes that stained negative by hematoxylin-eosin were examined with immunohistochemistry for micrometastases. Primary tumors were analyzed by immunohistochemistry for mp53 and TSP-1 expression. The t test and the Mann-Whitney U test were used to examine the mean difference in TSP-1 expression between tumors.

Main Outcome Measures  Mutant p53 expression, TSP-1 expression, and metastatic progression.

Results  Thirty-six of the 61 patients (59%) had nodal metastases shown by hematoxylin-eosin or immunohistochemistry in the sentinel node (N2, N1, N1mi, or N0[i+]). Patients with a truly negative sentinel node (pN0[i–][sn]) had significantly higher TSP-1 expression compared with those with some degree of nodal metastases (57.7 vs 30.1; P < .001). Acquisition of mp53 was associated with a decreased mean TSP-1 expression. Tumors without mp53 expression had a mean TSP-1 optical density value of 51.3 while tumors with elevated mp53 had a mean TSP-1 optical density value of 31.8 (P < .03).

Conclusions  Patients with primary colorectal cancer with low TSP-1 expression, with or without detection of mp53 gene product, are more likely to harbor lymph node metastasis than patients with higher expression. Patients with a truly negative sentinel node (pN0[i–][sn]) frequently have higher expression of TSP-1 that may have inhibited metastatic progression. Further studies will investigate the relationship between mp53, TSP expression, and disease progression.

Author Affiliations: Department of Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California (Drs Iddings and Bilchik and Ms Koda); McLaren Regional Medical Center, Michigan State University, Flint (Drs Grewal and Saha); and Oncotech Inc, Irvine, California (Dr Parker).