Wheeler T M, Rogers E, Aihara M, Scardino P T, Thompson T C
Department of Pathology, Baylor College of Medicine, Houston, TX 77030.
J Cell Biochem Suppl. 1994;19:202-7.
Chemoprevention trials in prostate cancer would involve excessively long follow-up if conventional endpoints of efficacy are used. Prostatic intraepithelial neoplasia (PIN) may be an appropriate surrogate endpoint for monitoring outcome during prostate cancer chemoprevention studies. To address the question of whether PIN could be stratified into "stable" PIN and PIN likely to progress to invasive cancer, we selected patients with a single focus of peripheral zone cancer with ipsilateral and contralateral high-grade PIN. Sixteen patients met these criteria from a series of 550 patients treated by radical prostatectomy. We examined the rate of apoptosis in PIN and prostate cancer tissues by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on hematoxylin and eosin stained histological sections. Significant differences (ANOVA: p < 0.05) were detected between foci of prostatic intraepithelial neoplasia contralateral to the cancer and the cancer itself. There was no difference in the apoptotic index between a given cancer and a focus of PIN ipsilateral to the tumor in the same section. However, the range of apoptotic indices overlapped in all categories. Apoptotic indices appear to parallel the biological activity of PIN and malignant prostatic tissue, but may be of little benefit when used alone in monitoring the outcome of chemopreventive therapy in an individual patient.
如果采用传统的疗效终点，前列腺癌的化学预防试验将需要过长的随访时间。前列腺上皮内瘤变（PIN）可能是前列腺癌化学预防研究中监测结果的合适替代终点。为了解决PIN是否可分为“稳定”PIN和可能进展为浸润性癌的PIN这一问题，我们选择了患有单一灶外周区癌且同侧和对侧有高级别PIN的患者。在一系列550例行根治性前列腺切除术的患者中，有16例符合这些标准。我们通过对苏木精和伊红染色的组织学切片上每百个细胞中的凋亡小体数量（凋亡指数）进行定量，来检查PIN和前列腺癌组织中的凋亡率。在癌灶对侧的前列腺上皮内瘤变灶与癌灶本身之间检测到显著差异（方差分析：p < 0.05）。在同一切片中，给定癌灶与肿瘤同侧的PIN灶之间的凋亡指数没有差异。然而，所有类别中凋亡指数的范围都有重叠。凋亡指数似乎与PIN和恶性前列腺组织的生物学活性平行，但单独用于监测个体患者化学预防治疗的结果时可能益处不大。
