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"Adapted from Zatterstrom et al., Head Neck 17(4), 312-318 (1995).

"Adapted from Zatterstrom et al., Head Neck 17(4), 312-318 (1995).

patients affected by HNSCC in various areas of the aereodi-gestive tract were examined [71]. The authors were not able to find a statistically significant difference between rate of angiogenesis in the tumors with local recurrence and rate of metastasis. However, analysis of a small number of cases, as well as the heterogeneity of the origin sites of the malignancies, may account for the discrepancy of these results.

In 1993, Gasparini and colleagues [72] assessed that 70 patients with locally advanced HNSCC, presenting loco-regional and distance metastases, displayed a significantly higher capillary density than those without metastatic diffusion. Increased angiogenesis was also correlated with relapse and metastasis in laryngeal squamous cell carcinoma [73]. Likewise, increased microvessel concentration was also found in premetastatic specimens from 66 patients diagnosed with squamous cell cancer of the oral cavity, thus suggesting that angiogenesis is likely to be an important independent predictor of nodal metastasis [74] (Fig. 7.3 and Table 7.2). However, opposing conclusions arose from a report by Leedy et al. [75], in which no correlation between tumor vascularity and nodal metastasis was determined in 57 patients affected by early (T1 and T2) tongue squamous cell carcinoma (Table 7.3). However, in an attempt to compare microvessel density in 33 late stage (T3 and T4) and metastatic versus early stage (T1 and T2) and nonmetastatic oral squamous cell carcinoma (OSCC) specimens, Alcalde and colleagues [76] observed a higher level of angiogenesis in the most advanced and invasive areas of the tumors. Likewise, another study confirmed the correlation between the count of microvessel to lymph node metastasis in 41 primary OSCC [77]. In contrast, two independent studies on T1 and T2-T4 OSCC, respectively, were performed by Gleich et al. [78,79]. In both analyses, the lack of a representative correlation between angiogenesis and either tumor aggressiveness or prognosis was detected, thereby concluding that oral tumor development may proceed independently from angiogenesis. However, it was also shown that the level of vascularity in oral carcinomas was significantly higher than that detected in normal oral tissue. Interestingly, a progressive increase in vascularity from normal to dysplastic to neoplastic tissues was found, thus suggesting that angiogenesis may be an early, rather than late, step in oral tumor progression [80] (Fig. 7.4).

40 60 80

Months {post treatment)

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