H&E and Ki-67 immunostaining of tumor tissue from nude mice xenografts. (a, c) Solid aggregates of highly atypical tumor cells showing large, round nuclei, prominent nucleoli and abundant cytoplasm were visible in tumors isolated from the placebo group. (b) In vorinostat-treated tumors, highly atypical tumor cells associated with abundant apoptosis were seen. Areas of apoptosis (marked by arrows) show tumor cells with smaller, dark nuclei with condensed chromatin and small rim of cytoplasm. Note the presence of vacuolated cytoplasm, fragmented tumor cells and isolated nuclei of tumor cells. (d) Aggregate of tumor cells with an apoptotic body characterized by dense eosinophilic cytoplasm and hyperchromatic nuclear fragments (marked by arrow). (e, f) More than 95% of tumor cells showed a positive nuclear immunoreaction for Ki-67, both in placebo and in vorinostat-treated tumors.