Rakozy C, Grignon D J, Sarkar F H, Sakr W A, Littrup P, Forman J
Department of Pathology, Karmanos Cancer Institute, Harper Hospital, and Wayne State University, Detroit, Michigan 48201, USA.
Mod Pathol. 1998 Sep;11(9):892-9.
Abnormalities in genes of the apoptotic pathway might contribute to survival in prostatic cancer (PCa) cells after radiation therapy (RT). We investigated the immunohistochemical expression of the products of the p53, p21WAF1, and bcl-2 genes in pre-RT and post-RT biopsy specimens from 38 patients with locally advanced PCa. All of the 38 patients underwent a uniform protocol of RT with or without neoadjuvant hormonal therapy. Immunohistochemical staining for expression of the products of the p53, p21WAF1, and bcl-2 genes was performed on material from pre-RT and post-RT specimens. Sufficient tissue for analysis was available from 25 of the pre-RT and 38 of the post-RT biopsy specimens. In benign prostatic epithelium, RT resulted in expression of p53 (2 [8%] of 25 pre-RT specimens vs. 15 [71%] of 21 post-RT specimens; P < .001) and increased expression of bcl-2 (1 [5%] of 18 pre-RT vs. 18 [86%] of 21 post-RT; P < .001). There was no change in the expression of p21WAF1 (1 [4.5%] of 22 pre-RT vs. 4 [17%] of 23 post-RT; P = NS). Post-RT specimens were positive for PCa in 24 (63%) of 38 cases. In the PCa tissue, p53 expression was seen in 10 (42%) of 24 pre-RT and 12 (63%) of 19 post-RT samples (P = NS). A significant upregulation of p53 was seen in the subgroup of patients who did not receive neoadjuvant hormonal therapy (9 [82%] of 11 vs. 3 [38%] of 8; P = .05). No significant change in p21WAF1 (5 [21%] of 24 vs. 5 [33%] of 15; P = NS), or bcl-2 (4 [18%] of 22 vs. 3 [21%] of 14; P = NS) expression was detected. There was no significant correlation between immunohistochemical expression of apoptosis-related markers and treatment failure. We concluded that RT induced upregulation of the bcl-2 and p53 gene products in benign prostatic tissue and that this likely reflected a protective mechanism in genetically unaltered epithelium. Increased p53 expression in PCa was only seen in patients without neoadjuvant hormonal treatment, indicating that the cancer cells with abnormal p53 were at least partially protected from RT-induced cell death.
凋亡途径相关基因的异常可能有助于前列腺癌细胞在放射治疗（RT）后存活。我们研究了38例局部晚期前列腺癌患者放疗前和放疗后活检标本中p53、p21WAF1和bcl-2基因产物的免疫组化表达。所有38例患者均接受了统一的放疗方案，部分患者接受了新辅助激素治疗。对放疗前和放疗后标本进行p53、p21WAF1和bcl-2基因产物表达的免疫组化染色。25例放疗前活检标本和38例放疗后活检标本中有足够的组织用于分析。在良性前列腺上皮中，放疗导致p53表达增加（25例放疗前标本中的2例[8%] vs. 21例放疗后标本中的15例[71%]；P <.001）以及bcl-2表达增加（18例放疗前标本中的1例[5%] vs. 21例放疗后标本中的18例[86%]；P <.001）。p21WAF1表达无变化（22例放疗前标本中的1例[4.5%] vs. 23例放疗后标本中的4例[17%]；P =无统计学意义）。38例放疗后标本中有24例（63%）前列腺癌呈阳性。在前列腺癌组织中，24例放疗前标本中的10例（42%）和19例放疗后标本中的12例（63%）可见p53表达（P =无统计学意义）。在未接受新辅助激素治疗的患者亚组中可见p53显著上调（11例中的9例[82%] vs. 8例中的3例[38%]；P =.05）。未检测到p21WAF1（24例中的5例[21%] vs. 15例中的5例[33%]；P =无统计学意义）或bcl-2（22例中的4例[18%] vs. 14例中的3例[21%]；P =无统计学意义）表达有显著变化。凋亡相关标志物的免疫组化表达与治疗失败之间无显著相关性。我们得出结论，放疗诱导良性前列腺组织中bcl-2和p53基因产物上调，这可能反映了基因未改变的上皮中的一种保护机制。仅在未接受新辅助激素治疗的患者中可见前列腺癌中p53表达增加，表明p53异常的癌细胞至少部分免受放疗诱导的细胞死亡。
