Cancers of the Digestive Tract

The prognostic value of microvessel density was little investigated in esophageal cancers. The study by Kumano et al. (103) suggested a significant association of high vascularization with the expansive and down-growth patterns of tumor growth patterns. Moreover, both carcinoma in situ and microinvasive cancers had higher microvessel counts, compared to the adjacent normal mucosa. Tanigawa et al. (104) stained intratumoral microvessels of 43 esophageal squamous cell carcinomas with anti-CD34 and fVIII-RA antibodies. Both the markers were found to be significant and independent prognostic markers. Regarding gastric carcinomas, the studies by Maeda et al. (105) and Tanigawa et al. (106) found that tumor angiogenesis was predictive of recurrence and time to progression and overall survival, respectively, in patients with invasive gastric carcinomas. Microvessel density was found to be significantly higher in VEGF-positive gastric carcinomas than in those VEGF-negative. Moreover, the patients with VEGF-positive tumors had a significantly poorer prognosis, with a particularly high frequency of hepatic metastases (107).

At least 5 studies (108-112) assessed the prognostic value of microvessel density in colorectal cancer (Table 6). Tumor angiogenesis was found to be significantly associated with transmural penetration and early death in a series of 48 patients with heterogeneous stages of rectal carcinoma (108). Subsequent studies by Tomisaki et al. (109) and Takebayashi et al. (110) suggested that the degree of angiogenesis of primary colorectal cancers is in prognostic value, and predictive of high probability of liver metastasis. Bossi et al. (111) observed that invasive carcinomas of the colorectum had a significantly higher vascularization of adenomas of normal mucosa. However, angiogenesis was not found to be of prognostic value in the series of 178 patients with heterogeneous stage of disease. Finally, the study by Lindmark et al. (112) compared three markers to highlight microvessels, and then assessed neovascularization of 212 consecutive patients with colorectal cancer using fVIII-RA. Contrary to the findings reported in all the other studies published up until now on angiogenesis and prognosis in solid tumors, the authors (112) observed that the patients with highly vascularized cancers had a significantly longer survival than those with low angiogenic tumors. However, these unexpected results may be impaired by some weaknesses in the methodology used (113). Studies performed by Vermeulen et al. (114) suggest that anti-CD31 antibody is the more sensitive marker for assessing angiogenesis in colorectal cancer, that the endothelial cells have a lower pro-

Table 6

Prognostic Value of Microvessel Density in Esophageal and Gastrointestinal Tumors

Median

Endothelial follow-up Prognostic

Author marker No. pts. Stage (mo) value Ref.

Esophageal cancer

Median

Endothelial follow-up Prognostic

Author marker No. pts. Stage (mo) value Ref.

Esophageal cancer

Tanigawa

CD34/fVIII-RA

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