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Sialyl Lewis X expression and lymphatic microvessel density in primary tumors of node-negative colorectal cancer patients predict disease recurrence.

Doekhie FS, Morreau H, de Bock GH, Speetjens FM, Dekker-Ensink NG, Putter H, van de Velde CJ, Tollenaar RA, Kuppen PJ - Cancer Microenviron (2008)

Bottom Line: 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).Our results are consistent with the notion that both lymphatic and hematogenous metastasis play a role in colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, K6-R, Leiden University Medical Center, Leiden, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus

Tumor cell invasion in lymphatic and blood vessels in colorectal tumors. Lymphatic vessel invasion seen on a hematoxylin and eosin stained section (a) and immunohistochemically stained section by the antibodies D2–40 (b); lymphatic vessels were brown stained by D2–40. Blood vessel invasion seen on a hematoxylin and eosin stained section (c) and immunohistochemically stained section by the antibodies CD31 (d); blood vessels were brown stained by CD31
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Fig3: Tumor cell invasion in lymphatic and blood vessels in colorectal tumors. Lymphatic vessel invasion seen on a hematoxylin and eosin stained section (a) and immunohistochemically stained section by the antibodies D2–40 (b); lymphatic vessels were brown stained by D2–40. Blood vessel invasion seen on a hematoxylin and eosin stained section (c) and immunohistochemically stained section by the antibodies CD31 (d); blood vessels were brown stained by CD31

Mentions: Lymphatic vessel invasion was seen in 8 of 96 (8%) D2–40 stained tumor sections (Fig. 3a,b) and blood vessel invasion was only seen in one of 96 (1%) sections stained with antibodies directed against CD31 (Fig. 3c,d). Seven of the 8 patients with lymphatic vessel invasion detected on the D2–40 stained sections had been recognized on the HE stained sections and the one tumor with blood vessel invasion was also seen on the HE stained section (Fig. 3g). These results show that morphological vaso-invasion scored on HE stained sections overestimated the actual blood and lymphatic vessel invasion as seen after immunohistochemical staining.Fig. 3


Sialyl Lewis X expression and lymphatic microvessel density in primary tumors of node-negative colorectal cancer patients predict disease recurrence.

Doekhie FS, Morreau H, de Bock GH, Speetjens FM, Dekker-Ensink NG, Putter H, van de Velde CJ, Tollenaar RA, Kuppen PJ - Cancer Microenviron (2008)

Tumor cell invasion in lymphatic and blood vessels in colorectal tumors. Lymphatic vessel invasion seen on a hematoxylin and eosin stained section (a) and immunohistochemically stained section by the antibodies D2–40 (b); lymphatic vessels were brown stained by D2–40. Blood vessel invasion seen on a hematoxylin and eosin stained section (c) and immunohistochemically stained section by the antibodies CD31 (d); blood vessels were brown stained by CD31
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Related In: Results  -  Collection

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Fig3: Tumor cell invasion in lymphatic and blood vessels in colorectal tumors. Lymphatic vessel invasion seen on a hematoxylin and eosin stained section (a) and immunohistochemically stained section by the antibodies D2–40 (b); lymphatic vessels were brown stained by D2–40. Blood vessel invasion seen on a hematoxylin and eosin stained section (c) and immunohistochemically stained section by the antibodies CD31 (d); blood vessels were brown stained by CD31
Mentions: Lymphatic vessel invasion was seen in 8 of 96 (8%) D2–40 stained tumor sections (Fig. 3a,b) and blood vessel invasion was only seen in one of 96 (1%) sections stained with antibodies directed against CD31 (Fig. 3c,d). Seven of the 8 patients with lymphatic vessel invasion detected on the D2–40 stained sections had been recognized on the HE stained sections and the one tumor with blood vessel invasion was also seen on the HE stained section (Fig. 3g). These results show that morphological vaso-invasion scored on HE stained sections overestimated the actual blood and lymphatic vessel invasion as seen after immunohistochemical staining.Fig. 3

Bottom Line: 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).Our results are consistent with the notion that both lymphatic and hematogenous metastasis play a role in colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, K6-R, Leiden University Medical Center, Leiden, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus