title: Sialyl Lewis X expression and lymphatic microvessel density in primary tumors of node-negative colorectal cancer patients predict disease recurrence.
abstract: Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX), vascular endothelial growth factor (VEGF)-C and VEGF-D expression; B) blood and lymphatic microvessel density (BMVD/LMVD); and C) the presence of blood and lymphatic vessel invasion. Thirty-six cases (disease recurrence within 5 years) and 72 controls (no disease recurrence for at least 5 years) were selected in a case-control design. Tumor sections were stained by antibodies CSLEX1 (sLeX), anti-VEGF-C, anti-VEGF-D, anti-CD31 (BMVD) or D2-40 (LMVD) to determine the parameters as mentioned above. A multivariate analysis showed sLeX expression and high LMVD (odds ratio 5.1, 95% confidence interval 1.3-20.0 and odds ratio 3.1, 95% confidence interval 1.0-10.0, respectively) to be independent factors predicting disease recurrence. Expression of sLeX correlated with liver metastases (P = 0.015). A high LMVD was related to regional intra-abdominal or intrapelvic metastases in lymph nodes and distant metastases other than in the liver and lungs such as peritoneum, bones, brain and adrenal glands (P = 0.004). A high BMVD in the invasive front correlated with lung metastases (P = 0.018). We show that high-risk node-negative colorectal cancer patients can be identified by primary tumor assessment for sLeX expression and LMVD. Our results are consistent with the notion that both lymphatic and hematogenous metastasis play a role in colorectal cancer.
authors.affiliation: Department of Surgery, K6-R, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Fania S
authors.initials: FS
authors.lastname: Doekhie
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Frank M
authors.initials: FM
authors.lastname: Speetjens
authors.forename: N Geeske
authors.initials: NG
authors.lastname: Dekker-Ensink
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen