Growth, microvessel density and tumor cell invasion of human colon adenocarcinoma under repeated treatment with hyperthermia and serotonin.

The intratumoral microvessel density of malignant breast cancer has been shown to be an important prognostic marker. In this study, we tested whether repeated treatment with hyperthermia and serotonin (5-hydroxytryptamine) reduces tumor growth and alters tumor histology of a colon adenocarcinoma, and whether capillary density in this tumor can also be regarded as an important prognostic marker. Previously we have shown that acute treatment of colon adenocarcinoma with hyperthermia, alone or in combination with serotonin, selectively constricted tumor microvessels, which could reduce blood flow and inhibit tumor growth. Fourteen days after human colon adenocarcinoma had been transplanted under the dorsal epidermis of the ear of athymic nude mice, the surgically unprepared tumor-bearing ear of the sodium-pentobarbital-anesthetized animal was treated with hyperthermia alone (group 1, 43 degrees C for 45 min), or with hyperthermia plus topically applied serotonin (1 mM/l, 43 degrees C for 45 min, group 2) twice per week for 5 weeks. Control animals were not treated (group 3). Histological slides (stained with hematoxylin/eosin) were prepared 42 days after implantation, for analysis of tumor grading, tumor cell invasion into the surrounding tissue and microvessels, and the number of intratumoral microvessels. Repeated hyperthermia inhibited tumor growth, reduced the number of intratumoral microvessels, did not change tumor cell invasion and increased the necrotic area. Hyperthermia and serotonin did not influence tumor growth, but strongly reduced cell invasion and the number of microvessels. The area of necrosis was very large. Thus, analysis of microvessel density in colon adenocarcinoma seems not to be an important tool for predicting therapeutic efficacy.