Aprikian A G, Sarkis A S, Fair W R, Zhang Z F, Fuks Z, Cordon-Cardo C
Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
J Urol. 1994 May;151(5):1276-80. doi: 10.1016/s0022-5347(17)35231-x.
Abnormalities of the TP53 gene are currently the most common genetic alterations associated with human malignancy. The study of altered patterns of p53 protein expression in primary prostate cancer has to date yielded a much lower incidence of alteration compared to bladder, colon, lung and breast cancer. However, the analysis of prostate cancer metastases has been limited. The objective of our study was to determine the prevalence of p53 nuclear accumulation in primary, metastatic and hormone refractory prostatic adenocarcinoma, and to characterize its relationship with conventional clinicopathological variables. We used 2 antibodies (mouse monoclonal PAb 1801 and rabbit polyclonal CM-1) and an immunohistochemical method in 93 paraffin embedded tumors (48 primary tumors, 29 lymph node metastases and 16 bone metastases) to assess p53 nuclear accumulation. Overall, p53 nuclear accumulation was observed in 19 tumors (20%), including 17 with PAb 1801 and CM-1 immunoreactivities, and 2 with CM-1 immunoreactivity only. The pattern of p53 immunoreactivity was heterogeneous in most tumors, with only 3 cases exhibiting homogeneous staining. Primary, lymph node and bone metastases exhibited p53 nuclear staining in 9 of 48 (19%), 2 of 29 (7%) and 8 of 16 (50%) cases, respectively (p = 0.003). In 6 of 10 primary hormone refractory tumors (60%) and in 3 of 38 primary hormone naive tumors (8%) p53 nuclear immunoreactivity was expressed (p = 0.002). P53 nuclear accumulation was significantly more common in higher grade primary tumors (p = 0.007). Our results suggest that p53 nuclear accumulation is relatively uncommon in prostate cancer. However, p53 nuclear accumulation appears to be associated with advanced stages of disease, as illustrated by its relatively higher occurrence in hormone refractory tumors and bone metastases. Furthermore, the significantly greater prevalence of p53 accumulation in bone metastases is currently the highest reported for prostate cancer.
TP53基因异常是目前与人类恶性肿瘤相关的最常见基因改变。与膀胱癌、结肠癌、肺癌和乳腺癌相比，原发性前列腺癌中p53蛋白表达改变模式的研究迄今显示改变发生率要低得多。然而，前列腺癌转移灶的分析一直很有限。我们研究的目的是确定p53核积聚在原发性、转移性和激素难治性前列腺腺癌中的发生率，并描述其与传统临床病理变量的关系。我们使用两种抗体（小鼠单克隆PAb 1801和兔多克隆CM-1）以及免疫组织化学方法，对93个石蜡包埋肿瘤（48个原发性肿瘤、29个淋巴结转移灶和16个骨转移灶）进行评估，以检测p53核积聚情况。总体而言，在19个肿瘤（20%）中观察到p53核积聚，其中17个同时具有PAb 1801和CM-1免疫反应性，2个仅具有CM-1免疫反应性。大多数肿瘤中p53免疫反应性模式是异质性的，只有3例显示均匀染色。原发性肿瘤、淋巴结转移灶和骨转移灶中p53核染色分别见于48例中的9例（19%）、29例中的2例（7%）和16例中的8例（50%）（p = 0.003）。10例原发性激素难治性肿瘤中有6例（60%）以及38例原发性激素初治肿瘤中有3例（8%）表达p53核免疫反应性（p = 0.002）。p53核积聚在高分级原发性肿瘤中明显更常见（p = 0.007）。我们的结果表明，p53核积聚在前列腺癌中相对不常见。然而，p53核积聚似乎与疾病的晚期阶段相关，激素难治性肿瘤和骨转移灶中其发生率相对较高就说明了这一点。此外，骨转移灶中p53积聚的显著更高发生率是目前前列腺癌报道中最高的。
