Kandioler Daniela, Zwrtek Ronald, Ludwig Carmen, Janschek Elisabeth, Ploner Meinhard, Hofbauer Friedrich, Kührer Irene, Kappel Sonja, Wrba Friedrich, Horvath Manfred, Karner Josef, Renner Karl, Bergmann Michael, Karner-Hanusch Judith, Pötter Richard, Jakesz Raimund, Teleky Bela, Herbst Friedrich
Department of Surgery, University of Vienna, Vienna, Austria.
Ann Surg. 2002 Apr;235(4):493-8. doi: 10.1097/00000658-200204000-00006.
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.
Recent studies show that p53 may be a determinant of radiosensitivity being required for induction of apoptosis in case of radiation-induced DNA damage.
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.
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 postradiotherapy 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.
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.
评估并比较p53基因分析与p53免疫组化染色对可手术直肠癌术前25 Gy短期放疗反应的预测能力。
近期研究表明，p53可能是放射敏感性的决定因素，在辐射诱导的DNA损伤情况下，它是诱导细胞凋亡所必需的。
分析64例直肠癌患者放疗前的活检样本。通过对2至10号外显子进行完全直接测序来检测p53基因的遗传改变。通过免疫组化染色评估核磷蛋白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联。
45%的肿瘤存在p53基因突变。p53基因正常的患者具有显著的生存优势。比较放疗前后的T分期，仅在p53基因型正常的患者中观察到分期降低。突变型p53基因型在指示放疗后T分期的疾病稳定方面具有高度特异性。61%检测到蛋白过表达。p53蛋白过表达与生存或反应无关。免疫组化与测序之间的一致性仅为0.51。
作者表明短期放疗后可能会出现分期降低，但仅在p53基因正常的肿瘤中可见。此外，p53基因型而非p53免疫组化可预测术前短期放疗的反应和患者生存。
