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 be en shown to be an important prognostic marker. In this study, we teste d whether repeated treatment with hyperthermia and serotonin (5-hydrox ytryptamine) reduces tumor growth and alters tumor histology of a colo n adenocarcinoma, and whether capillary density in this tumor can also be regarded as an important prognostic marker. Previously we have sho wn that acute treatment of colon adenocarcinoma with hyperthermia, alo ne or in combination with serotonin, selectively constricted tumor mic rovessels, which could reduce blood flow and inhibit tumor growth. Fou rteen days after human colon adenocarcinoma had been transplanted unde r 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/ 1, 43 degrees C for 45 min, group 2) twice per week for 5 weeks. Contr ol animals were not treated (group 3). Histological slides (stained wi th hematoxylin/eosin) were prepared 42 days after implantation, for an alysis of tumor grading, tumor cell invasion into the surrounding tiss ue and microvessels, and the number of intratumoral microvessels. Repe ated hyperthermia inhibited tumor growth, reduced the number of intrat umoral 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 microvess els. The area of necrosis was very large. Thus, analysis of microvesse l density in colon adenocarcinoma seems not to be an important tool fo r predicting therapeutic efficacy.