Yang Y, Forslund A, Remotti H, Lönnroth C, Andersson M, Brevinge H, Svanberg E, Lindnér P, Hafström L, Naredi P, Lundholm K
Department of Oncology, Nanfang University Hospital, Guangzhou City, People's Republic of China.
Cancer. 2001 Feb 15;91(4):727-36.
The appearance of p53 mutations in colorectal carcinoma was determined, independent of differentiation and tumor stage of the primary tumors, in relation to the survival of patients who were scheduled to undergo liver resection.
Tumor material was analyzed for p53 mutations in primary colorectal tumors and subsequent liver metastases from 41 consecutive patients who were scheduled to undergo surgical liver resection. DNA sequencing and immunohistochemical staining of p53 protein within tumor nuclei were performed.
Primary tumors displayed p53 mutations within exons 5-9 in 41% of patients. No mutations were found in exons 4, 10, or 11. Forty-one percent of metastatic lesions had the same single mutation that was found in the primary tumor, whereas 11% of metastatic lesions had one additional mutation within exons 5-9; 22% had mutations only in their liver metastases, whereas corresponding primary tumors displayed wild-type p53. None of the patients had mutated p53 in their primary tumor and wild type in their metastases. Survival after undergoing liver resection was correlated negatively (P < 0.05-0.01) with Duke Stages A-D classification of the primary tumors, tumor differentiation, and radicality (> 0.7-0.8 mm) of resected liver metastases.
The presence of p53 mutations in patients with metastatic lesions was related significantly (P < 0.003) to better survival after the patients underwent liver resection compared with patients with wild type p53 in their metastatic lesions. This finding was not related to covariates, such as Duke classification, tumor differentiation, type of liver metastasis, or metastatic radicality during resections. Explanations for this unexpected finding remain unclear, although the authors speculate that occult tumor cells with p53 mutations may be less responsive to growth factor(s) exposure during hepatic regeneration after resection.
在计划接受肝切除的患者中，研究了结直肠癌中p53突变的出现情况，该情况独立于原发肿瘤的分化程度和肿瘤分期与患者生存率的关系。
对41例计划接受肝切除手术的连续患者的原发结直肠癌肿瘤及随后的肝转移灶进行p53突变分析。对肿瘤细胞核内的p53蛋白进行DNA测序和免疫组化染色。
41%的患者原发肿瘤在第5至9外显子中显示p53突变。在第4、10或11外显子中未发现突变。41%的转移灶具有与原发肿瘤相同的单一突变，而11%的转移灶在第5至9外显子中有另外一个突变；22%的转移灶仅在肝转移灶中有突变，而相应的原发肿瘤显示p53野生型。没有患者原发肿瘤p53突变而转移灶为野生型。肝切除术后的生存率与原发肿瘤的杜克分期A - D分类、肿瘤分化程度以及切除的肝转移灶的根治性（> 0.7 - 0.8 mm）呈负相关（P < 0.05 - 0.01）。
与转移灶中p53为野生型的患者相比，转移灶中存在p53突变的患者在接受肝切除术后的生存率显著更高（P < 0.003）。这一发现与诸如杜克分类、肿瘤分化程度、肝转移类型或切除术中转移灶的根治性等协变量无关。尽管作者推测切除后肝再生过程中，具有p53突变的隐匿肿瘤细胞可能对生长因子暴露反应较小，但这一意外发现的原因仍不清楚。
