TP53 genotype but not p53 immunohistochemical result predicts response to Preoperative short-term radiotherapy in rectal cancer
TP53 genotype but not p53 immunohistochemical result predicts response to Preoperative short-term radiotherapy in rectal cancer
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DOI：
10.1097/00000658-200204000-00006
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发表时间：
2002-04-01
影响因子：
9
通讯作者：
Herbst, F
中科院分区：
文献类型：
--
作者：
Kandioler, D;Zwrtek, R;Herbst, F
目的 评估和比较 p53 基因分析与 p53 免疫组织化学染色对可手术直肠癌术前 25 Gy 短期放疗反应的预测能力。 背景资料摘要 最近的研究表明，在辐射引起的 DNA 损伤的情况下，p53 可能是诱导细胞凋亡所需的放射敏感性的决定因素。 方法 对 64 例直肠癌患者的放射前活检样本进行分析，p53 基因的遗传改变通过外显子 2 至 10 的完整直接测序来检测。通过免疫组织化学染色评估核磷蛋白 p53 的表达。结果分别与切除标本的组织病理学和随访数据相关。结果 p53 基因突变存在于 45% 的肿瘤中。 p53 基因正常的患者具有显着的生存优势。比较放疗前和放疗后的 T 类别，仅在 p53 基因型正常的患者中观察到减少。突变的 p53 基因型在指示辐射后 T 类疾病稳定方面具有高度特异性，检测到 61% 的蛋白质过度表达。 p53 蛋白的过度表达与生存或反应无关。免疫组化和测序之间的一致性仅为0.51。结论作者表明，短期放射后可能发生降期，但仅见于p53基因正常的肿瘤。此外，p53 基因型而非 p53 免疫组织化学可预测术前短期放疗的反应和患者生存。
Objective To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer.Summary Background Data Recent studies show that p53 may be a determinant of radiosensitivity being required for induction of apoptosis in case of radiation-induced DNA damage.Methods Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed, Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively.Results Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and post radiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation, Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51.Conclusions The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.