Kamoshida S, Suzuki M, Shimomura R, Sakurai Y, Komori Y, Uyama I, Tsutsumi Y
Department of Pathology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Br J Cancer. 2007 Jan 29;96(2):277-83. doi: 10.1038/sj.bjc.6603546. Epub 2007 Jan 9.
High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers were immunostained for TS and p53 protein after appropriate antigen retrieval. Fifty-one cases without neoadjuvant chemotherapy were also studied. In the pretreatment biopsies, high expression of TS was seen in 8% of the histologic responders, in 28% of the nonresponders and in 31% of the controls. High expression of p53 was observed in 56% of the nonresponders, but in 8% of the responders and in 29% of the controls (P<0.01 and P<0.05, respectively). The TS- and/or p53-high phenotype was seen in 76% of the nonresponders and in 54% of the controls, but in 8% of the responders (P<0.0001 and P<0.005, respectively). The data of the surgical specimens were consistent with those of the pretreatment biopsies. These results suggest that immunostaining for TS and p53 protein is useful for pretreatment selection of gastric cancer patients unresponsive to S-1/cisplatin chemotherapy.
胸苷酸合成酶(TS)的高表达和p53的失活据称与化疗耐药相关。作者评估了新辅助S-1/顺铂化疗治疗的胃癌中TS和p53的表达。对41例胃癌患者治疗前活检和手术标本的石蜡切片进行适当抗原修复后,对TS和p53蛋白进行免疫染色。还研究了51例未接受新辅助化疗的病例。在治疗前活检中,组织学反应者中8%、无反应者中28%以及对照组中31%可见TS高表达。无反应者中56%观察到p53高表达,但反应者中为8%,对照组中为29%(分别为P<0.01和P<0.05)。无反应者中76%以及对照组中54%可见TS和/或p53高表型,但反应者中为8%(分别为P<0.0001和P<0.005)。手术标本的数据与治疗前活检的数据一致。这些结果表明,TS和p53蛋白免疫染色有助于对S-1/顺铂化疗无反应的胃癌患者进行治疗前选择。