Fujino M, Dosaka-Akita H, Harada M, Hiroumi H, Kinoshita I, Akie K, Kawakami Y
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Cancer. 1995 Dec 15;76(12):2457-63. doi: 10.1002/1097-0142(19951215)76:12<2457::aid-cncr2820761209>3.0.co;2-x.
Alterations of the p53 gene are one of the most common genetic changes in various types of cancer, including lung cancer. Abnormalities in the ras genes, including point mutations and overexpression, are another common feature in the molecular biology of lung cancer and are associated with a poorer prognosis. The authors' purpose was to determine expression of the mutated p53 gene in nonsmall cell lung cancer (NSCLC) specimens that were studied for expression of ras p21 and to document whether altered p53 expression was also an important factor for survival.
Ninety-six patients with NSCLC underwent surgical resection between 1977 and 1985, 63 of whom received postoperative combination chemotherapy. None received radiation therapy. Tumor specimens were analyzed for altered p53 expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between p53 expression and survival.
Fifty-six (58%) of 96 tumor specimens showed altered p53 expression, and 91 patients were analyzed for survival. Altered p53 expression did not correlate with clinicopathologic characteristics except for postsurgical pathologic tumor (pT) classification. The patients with altered p53 expression survived for a significantly shorter period after surgery than those without p53 expression, including all patients who underwent resection and potentially curative resection (P = 0.02 and P = 0.048, respectively, generalized Wilcoxon test). Multivariate analysis showed independent prognostic significance for altered p53 expression (hazard ratio [HR] = 1.72, P = 0.04) and surgical cure (HR = 4.69, P < 0.001). The combined analysis of mutated p53 and ras p21 expression in the same tumor specimens revealed that patients with p53- and ras p21-negative tumors survived the longest among those with different p53 and ras p21 features (P = 0.005, generalized Wilcoxon test).
Altered p53 expression is a significant and independent negative prognostic factor for patients with surgically resected NSCLC: Combined immunohistochemical analysis of mutated p53 and ras p21 expression can divide patients with NSCLC into more accurate prognostic groups. If the current findings can be confirmed in larger prospective studies, combined immunohistochemical analysis of mutated p53 and ras p21 expression can be a useful clinical tool for stratifying patients with NSCLC into accurate prognostic groups and for identifying the population with a different risk of recurrence.
p53基因改变是包括肺癌在内的各类癌症中最常见的基因变化之一。ras基因异常，包括点突变和过表达，是肺癌分子生物学的另一个常见特征，且与较差的预后相关。作者的目的是确定在研究了ras p21表达的非小细胞肺癌（NSCLC）标本中突变型p53基因的表达情况，并记录p53表达改变是否也是生存的一个重要因素。
96例NSCLC患者在1977年至1985年间接受了手术切除，其中63例接受了术后联合化疗。无人接受放疗。通过免疫组织化学分析肿瘤标本中p53表达的改变。进行单因素和多因素分析以评估p53表达与生存之间的关联。
96例肿瘤标本中有56例（58%）显示p53表达改变，对91例患者进行了生存分析。除了术后病理肿瘤（pT）分类外，p53表达改变与临床病理特征无关。p53表达改变的患者术后存活时间明显短于p53未表达的患者，包括所有接受切除和可能根治性切除的患者（广义Wilcoxon检验，分别为P = 0.02和P = 0.048）。多因素分析显示p53表达改变具有独立的预后意义（风险比[HR] = 1.72，P = 0.04）和手术治愈情况（HR = 4.69，P < 0.001）。对同一肿瘤标本中突变型p53和ras p21表达的联合分析显示，在具有不同p53和ras p21特征的患者中，p53和ras p21均阴性的肿瘤患者存活时间最长（广义Wilcoxon检验，P = 0.005）。
p53表达改变是手术切除的NSCLC患者的一个重要且独立的负面预后因素：突变型p53和ras p21表达的联合免疫组织化学分析可将NSCLC患者分为更准确的预后组。如果当前研究结果能在更大规模的前瞻性研究中得到证实，突变型p53和ras p21表达的联合免疫组织化学分析可成为一种有用的临床工具，用于将NSCLC患者分层为准确的预后组，并识别具有不同复发风险的人群。
