대장암 환자에서 혈청 p53 항체 측정의 의의
Detection of Serum Anti-p53 Antibodies and Their Significance in Patients with Colorectal Cancer
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배경 : 종양억제유전자 p53의 돌연변이로 인해 축적된 p53 단백은 특이면역반응을 일으켜 혈청 내 p53 항체를 생성한다. 유방암, 난소암, 폐암 등에서 p53 항체가 종양표지자로서 예후와 관련되어 평가되어왔다. 대장암 환자에서 혈청 p53 항체를 측정하고다른 종양표지자와의 연관성 및 임상적 의의를 평가하고자 하였다.방법 : 74명의 대장암 환자에서 술전에 채취한 혈청을 사용하여효소면역법으로 p53 항체, CEA, CA19-9을 측정하였다. 동시에일부 절제된 종양 조직의 p53 단백발현을 면역조직화학학적으로염색하였다.결과 : 혈청 p53항체는 대장암 환자의 34% (25/74)에서 양성이었고, 정상인에서는 모두 음성이었다. 혈청 p53 항체 양성과조직 p53 단백 발현 사이에 유의한 관계가 있었다. CEA, CA19-9은 각각 환자군의 38%, 11%에서 양성이었고 이들 종양표지자들간에는 유의한 연관성이 없었다. p53 항체 양성과 음성군에서 종양의 위치, 크기, 조직학적 분류, 침범정도, 혈관 침범, 림프절 침윤, 절제 부위 침범, 원격 전이 유무, 생존 기간에서 유의한 차이는 없었다. 결론 : 혈청 p53 항체는 단독적인 예후 인자로 사용하기에는 부적절하며, 기존의 종양표지자와 달리 발생기전과 관련된 종양의 생물학적 표지자로서 p53 유전자의 변이를 반영하는 것으로 생각된다. 혈청 p53 항체는 높은 특이도를 가지고 있어 향후 이들 환자의 절제 후 p53 항체의 측정을 통해 경과관찰 용도의 사용가능성에 대한 연구가 필요할 것으로 생각된다.
Abstract
Background : Mutations of the tumor suppressor gene p53 cause subsequent cellular accumulation of p53 gene product and a specific immunologic response. Detection of circulating antibodies against p53 protein has been evaluated for a tumor marker or prognostic factor for several cancers including those of the breast, stomach, ovary and lung. Methods : Serum samples from 74 colorectal cancer patients were obtained preoperatively and anti-p53 antibody was measured by enzyme immunoassay (Anti-P53 ELISA II: PharmaCell, France). Carcinoembryonic antigen (CEA) and Carbohydrate antigen (CA) 19-9 were measured in parallel. Tissue p53 protein expression was examined by immunohistochemical staining. Results : Anti-p53 antibodies were positive in the serum from 34% (25/74) of patients, but normal controls were all negative. Anti-p53 antibodies were significantly associated with p53 protein overexpression. CEA and CA19-9 were detected in 38% and 11%, respectively. There was no correlation among anti-p53 antibody, CEA and CA19-9. No differences were found between the anti-p53 antibody positive and negative groups in the following parameters: tumor site, histologic grades, Dukes stages, margin invasion, vessel invasion, lymph node and distant metastasis, and survival duration. Conclusions : The measurement of serum anti-p53 antibody is not suitable for preoperative markers of prognostic significance, but can be used as a simple serological marker for detection of p53 alteration. There should be more studies of the serum p53 antibody as a possible marker for postoperative monitoring in colorectal cancer.
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