Cell Proliferation of Human Bladder Tumors

The cell proliferation of bladder tumors was assessed via an immunohistochemical technique using anti-bromodeoxyuridine (BrdUrd) antibody. The incorporation of the thymidine analogue, BrdUrd, into DNA synthesis phase was performed by an in vitro labeling technique. The percentage of labeled S-phase cells was expressed as the labeling index (LI). Discrimination between BrdUrd-labeled and unlabeled cells was easy because of the absence of background staining. The average LI obtained using this method in normal, normal epithelium bearing bladder tumors and cystitis was 5.0%, 4.0% and 5.0%, respectively. On the other hand, LI in bladder tumors was 13.0%, while the difference from non-malignant bladder epithelium was significant. As in high grade tumors, the labeled cells distributed throughout both the basal and surface layers of epithelium, compared to low grade tumors and controls. However, there was some variation in the distribution pattern within the same tumor depending on the histological site. On the other hand, the higher S-phase fraction was found in high grade or invasive bladder tumors. Bladder tumors with lymph node involvement had higher LI than those without the involvement. In patients who underwent TUR, the LI was as high as 10.0% in the recurrent group compared with 7.3% in the non-recurrent group. Moreover, in the total cystourethrectomy group, higher LI's were obtained in a patient dying of cancer (20.0%) and a patient with postoperative metastasis (21.0%) than in the non-recurrent group (14.8%). The high frequency of S-phase cells within tumor tissue appears to indicate a more malignant potential and thus a poor prognosis. Although further studies are required for its full significance, the measurement of BrdUrd labeling index by in vitro labeling method promises to afford useful information regarding the biological behavior of bladder tumors.