CAJ | 학술논문

目的：探讨P53、Ki-67和人表皮生长因子受体2（HER2）蛋白检测在进展期食管胃结合部腺癌患者新辅助化疗疗效的预测价值。方法收集2010年6月至2013年12月间于河南省安阳市肿瘤医院行SOX方案（奥沙利铂加替吉奥）新辅助化疗的72例SiewertⅡ型食管胃结合部腺癌患者化疗前的活检标本及临床病理资料。按照新辅助化疗疗效分为有效组（完全缓解加部分缓解）和无效组（疾病稳定加疾病进展）。用免疫组织化学方法检测两组患者P53、Ki-67和HER2蛋白的表达情况，分析不同蛋白表达情况与新辅助化疗疗效的关系。结果全组72例患者均完成2个周期的SOX方案新辅助化疗，SOX新辅助化疗有效组35例[完全缓解5例（6．9％）、部分缓解30例（41．7％）]、无效组37例[疾病稳定31例（43．1％）、疾病进展6例（8．3％）]。与新辅助化疗无效组相比，有效组的P53蛋白表达阳性率明显降低[25．0％（7／35）比45．9％（17／37），P＝0．020]，Ki-67蛋白表达阳性率明显增加[77．1％（27／35）比43．2％（16／37），P＝0．003]；而两组HER2蛋白阳性率的差异无统计学意义[42．9％（15／35）比21．6％（8／37），P＝0．053]。多因素分析结果显示，Ki-67是影响食管胃结合部腺癌新辅助化疗疗效的独立影响因素（P＝0．015）。Spearman秩相关分析显示，Ki-67表达与HER2表达呈正相关（r＝0．259，P＝0．028）；而Ki-67与P53、P53与HER2的表达均无明显相关性（均P＞0．05）。结论 SOX方案新辅助化疗治疗食管胃结合部腺癌安全、有效，其中Ki-67高表达和P53低表达患者的化疗有效率更高，可作为预测化疗疗效的参考指标；这2种蛋白表达无相关性，可共同检测以提高预测价值。
목적：탐토P53、Ki-67화인표피생장인자수체2（HER2）단백검측재진전기식관위결합부선암환자신보조화료료효적예측개치。방법수집2010년6월지2013년12월간우하남성안양시종류의원행SOX방안（오사리박가체길오）신보조화료적72례SiewertⅡ형식관위결합부선암환자화료전적활검표본급림상병리자료。안조신보조화료료효분위유효조（완전완해가부분완해）화무효조（질병은정가질병진전）。용면역조직화학방법검측량조환자P53、Ki-67화HER2단백적표체정황，분석불동단백표체정황여신보조화료료효적관계。결과전조72례환자균완성2개주기적SOX방안신보조화료，SOX신보조화료유효조35례[완전완해5례（6．9％）、부분완해30례（41．7％）]、무효조37례[질병은정31례（43．1％）、질병진전6례（8．3％）]。여신보조화료무효조상비，유효조적P53단백표체양성솔명현강저[25．0％（7／35）비45．9％（17／37），P＝0．020]，Ki-67단백표체양성솔명현증가[77．1％（27／35）비43．2％（16／37），P＝0．003]；이량조HER2단백양성솔적차이무통계학의의[42．9％（15／35）비21．6％（8／37），P＝0．053]。다인소분석결과현시，Ki-67시영향식관위결합부선암신보조화료료효적독립영향인소（P＝0．015）。Spearman질상관분석현시，Ki-67표체여HER2표체정정상관（r＝0．259，P＝0．028）；이Ki-67여P53、P53여HER2적표체균무명현상관성（균P＞0．05）。결론 SOX방안신보조화료치료식관위결합부선암안전、유효，기중Ki-67고표체화P53저표체환자적화료유효솔경고，가작위예측화료료효적삼고지표；저2충단백표체무상관성，가공동검측이제고예측개치。
Objective To investigate the predictive value of P53, Ki-67, HER2 protein detection in neoadjuvant chemotherapy for adenocarcinoma of gastroesophageal junction (AGEJ). Methods Preoperative biopsy specimens and clinical data of 72 patients of locally advanced Siewert ⅡAGEJ between June 2010 and December 2013 were reviewed. All the patients received SOX scheme neoadjuvant chemotherapy, and were divided into effective group (complete response plus partial response) and ineffective group (stable disease plus progressive disease). Expressions of above 3 proteins were detected by immunohistochemistry in all the patients before neoadjuvant chemotherapy. The relationship between various proteins and efficacy of chemotherapy was analyzed by univariate and logistic multivariate regression analyses. Results All the 72 patients successfully completed 2 cycles of SOX neoadjuvant chemotherapy, among them, 5 cases (6.9%) with complete response, 30 cases (41.7%) with partial response, 31 cases(43.1%) with stable disease, 6 cases(8.3%) with progressive disease, including 35 cases in effective group and 37 cases in ineffective group. Compared with ineffective group, the positive expression rate of P53 was significantly reduced (25.0% vs. 45.9%, P=0.020), and that of Ki-67 significantly increased (77.1% vs. 43.2%, P=0.003), however, there was no significant difference in the expression rate of HER2 between the two groups (P>0.05). Multivariate analysis showed that Ki-67 was the independent predictive factor for the efficacy of neoadjuvant chemotherapy (P=0.015). Spearman rank correlation showed that Ki-67 expression was positively correlated with HER2 expression (r=0.259, P=0.028), but P53 expression was not correlated with Ki-67 or HER2 (r=0.140, 0.042, P=0.240, 0.725, respectively). Conclusions SOX neoadjuvant chemotherapy is safe and effective for AGEJ, especially for patients with depressed expression of P53 and elevated expression of Ki-67, which both may be used as reference for the prediction of chemotherapy efficacy. There is no correlation between P53 and Ki67 proteins , so combined detection may improve the predictive value.