Expression of P63 and its correlation with prognosis in diffuse large B-cell lymphoma: a single center experience
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RESEARCH
Open Access
Expression of P63 and its correlation with prognosis in diffuse large B-cell lymphoma: a single center experience Wan-Ming Hu1,2,3,4†, Jie-Tian Jin1,2,3†, Chen-Yan Wu1,2,3, Jia-Bin Lu1,2,3, Li-Hong Zhang1,2,3, Jing Zeng1,2,3* and Su-Xia Lin1,2,3*
Abstract Background: Large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma among adults. In some cases, DLBCL may seem similar to carcinoma cells, presenting a round, oval, or polygonal shape and clear nuclei. We found that the expression of P63 accounted for a considerable proportion of DLBCL cases. Under the circumstances, P63 expression may lead to a misdiagnosis, especially with a small biopsy. We aim to investigate the expression status and prognostic significance of P63 in a cohort of Chinese DLBCL patients. Methods: P63, ΔNP63(P40), P53 and Ki67 were detected by immunohistochemistry (IHC). A ROC curve was adopted to find the best cut-off value for positive P63/P53 expression and high Ki67 expression. We defined P53 as positive when ≥50% of the tumor cells showed staining. The relationship between P63 and P53/Ki67 expression was examined. Time-to-event endpoints were estimated according to the Kaplan-Meier method. Moreover, multivariate analyses were conducted to evaluate the prognostic factors in DLBCL. Results: Out of all the 159 DLBCL cases, 76 (47.8%) expressed P63 in the nuclei, while 41 (25.8%) were determined to have high expression by using a ROC cut-off value “≥6”. Examination of the different P63 isoforms revealed that the ΔNP63(P40) was unclearly and weakly expressed in only 3 cases, showing a fuzzy yellow cytoplasm. P63 expression was not correlated with subtype (GCB or non-GCB) or P53 but was correlated with a high proliferative index (Ki67). KaplanMeier analyses revealed that P63 expression was correlated with overall survival, and P63 positive cases showed poor survival outcomes (P75%”, and the staining intensity was scored as “0 for no staining, 1 for light yellow, 2 for yellowish brown, and 3 for brown”. The ROC curve was used to find the cut-off value of P63/P53 positive expression and Ki67 high expression. Using the ROC curve, we defined the following: P53 was positive when ≥50% of tumor cells showed staining, a positive P63 expression value was determined when “P63 expression≥6”, and Ki67 high expression was determined when “Ki67 ≥ 80%”. TCGA dataset
The TCGA (The Cancer Genome Atlas) cohort of 47 DLBCL patients with detailed clinical information was downloaded from the public database (https://tcga-data. nci.nih.gov/tcga/tcgaDownload.jsp) and analyzed with the GEPIA tool [9] (http://gepia.cancer-pku.cn/). Statistical analysis
The relationship between P63, P53, and Ki67 expression and clinic-pathological parameters was evaluated by a Chi-square test. The Kaplan-Meier method was used to draw the survival curves, and they were compared by log-rank test. Univariate and/or multivariate Cox regression analyses were used to assess the influence of variables on survival. P < 0.05 was defined as signific
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