Autor: |
Shi YF; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China., Gao ZF; Department of Pathology, Peking University Third Hospital, Beijing 100191, China Department of Pathology, Beijing Boren Hospital, Beijing 100070, China., Li XH; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China., Guo LG; Department of Pathology, Beijing Boren Hospital, Beijing 100070, China., Zheng QL; Medical Laboratory of Molecular Diagnostic Laboratory, Beijing Boren Hospital Department, Beijing 100070, China., Long MP; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China., Deng LJ; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) , Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China., Du TT; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) , Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, China., Jia L; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) , Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China., Zhao W; Clinical Laboratory Center, Capital Medical University, Beijing 100069, China., Song XX; Department of Pathology, Hebei Eye Hospital, Shijiazhuang 054001, China., Li M; Department of Pathology, Peking University Third Hospital, Beijing 100191, China. |
Abstrakt: |
Objective: To explore the feasibility of predicting TP53 mutation risk by immunohistochemical staining (IHC) pattern of P53 in Chinese diffuse large B-cell lymphoma (DLBCL) and its correlation with a prognostic difference. Methods: Between January 2021 and December 2021, 51 DLBCL cases at Beijing Boren Hospital were gathered. These cases had both IHC and next-generation sequencing (NGS) results. IHC classified the P53 protein expression pattern into a loss (<1% ) , diffuse (>80% ) , and heterogeneous (1% -80% ) . The sensitivity and specificity of the predicting TP53 mutation by IHC were assessed by comparing the results of the NGS, and the TP53 high mutation risk group included both loss and diffuse expression of P53. From June 2016 to September 2019, Peking University Cancer Hospital collected 131 DLBCL cases with thorough clinicopathological and follow-up data. From their tumor blocks, tissue microarray blocks were made for IHC evaluation of P53 expression pattern, and prognosis effect of P53 studies. Results: Among 51 cases with both IHC and NGS results, 23 cases were classified as TP53 high mutation risk (7 cases loss and 16 cases diffuse) , 22/23 cases were proved with mutated TP53 by NGS. Only 1 of the 28 cases classified as TP53 low mutation risk was proved with mutated TP53 by NGS. IHC had a sensitivity and specificity of 95.7% and 96.4% for predicting TP53 mutation. NGS identified a total of 26 TP53 mutations with a mutation frequency of 61.57% (13.41% -86.25% ) . In the diffuse group, 16 missense mutations and 2 splice mutations were detected; 6 truncating mutations and 1 splice mutation were detected in the loss group; 1 truncating mutation was detected in the heterogeneous group. Multivariate analysis demonstrated that TP53 cases with high mutation risk have impartial adverse significance for the 131 patients included in survival analysis ( HR =2.612, 95% CI 1.145-5.956, P =0.022) . Conclusion: IHC of P53 exhibiting loss (<1% ) or diffuse (>80% ) pattern indicated TP53 high mutation risk, IHC can predict TP53 mutation with high specificity and sensitivity. TP53 high mutation risk is an independent predictor for adverse survival. |