p21 蛋白在预测胰腺内分泌肿瘤肝转移方面优于临床病理标准。

p21 Protein Outperforms Clinico-pathological Criteria in Predicting Liver Metastases in Pancreatic Endocrine Tumors.

机构信息

Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A.

Division of Neuroendocrine Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A.

出版信息

Cancer Genomics Proteomics. 2023 Nov-Dec;20(6):522-530. doi: 10.21873/cgp.20402.

DOI:10.21873/cgp.20402

PMID:37889062

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10614061/

Abstract

BACKGROUND/AIM: P21 is a cyclin-dependent kinase inhibitor regulating the cell cycle as a tumor suppressor. Using a p21 immunohistochemistry (IHC) assay, we compared tumor p21 levels with conventional clinico-pathological criteria in primary pancreatic endocrine tumor subsets with and without liver metastases.

MATERIALS AND METHODS

Sections from tissue microarray (TMA) including 13 archival metastatic primary and 18 non-metastatic primary pancreatic endocrine carcinomas/tumors (MP-PECAs/NMP-PETs) were stained with a monoclonal anti-p21 primary antibody. Tumor p21 IHCs were scored as the sum of intensity (0-3) and proportion scores (0-5) (Total Allred score: 0-8), and as p21% labelling index in the tumor. ROC curve analysis was used for most optimal p21 score cut-off (4 or >) and Fisher's exact test was used to compare the association among tumor p21 scores, conventional prognostic criteria, and liver metastases.

RESULTS

For PET/PECA patients, mean ages were 55.6 years (27-73) and 49.3 years (28-71), M/F ratios were 7/11 and 7/6. Mean p21 labelling index (%) for MP- PECAs was 24% (range=3-63%) vs. 9% for NMP-PETs (range=1-25%) (p=0.022). The mean p21 index in MP-PECAs was significantly higher (24%) as compared to PIs (7%) (p=0.0047). Using a p21 Allred score of ≥4, high p21 IHC score had strong association with the presence of liver metastases (p-value <0.001). High tumor p21 IHC score had a 93% sensitivity, 68% specificity, 78% predictive accuracy, 66% positive, and 94% negative predictive values.

CONCLUSION

In patients with primary PETs, p21 IHC is superior to conventional criteria in predicting presence or absence of liver metastases.

摘要

背景/目的：P21 是一种细胞周期依赖性激酶抑制剂，作为肿瘤抑制因子调节细胞周期。我们使用 p21 免疫组化（IHC）检测，比较了有和无肝转移的原发性胰腺内分泌肿瘤亚组的肿瘤 p21 水平与传统临床病理标准。

材料和方法

使用组织微阵列（TMA）中的切片，包括 13 例转移性原发性和 18 例非转移性原发性胰腺内分泌癌/肿瘤（MP-PECAs/NMP-PETs），用单克隆抗 p21 抗体进行染色。肿瘤 p21 IHC 评分作为强度（0-3）和比例评分（0-5）的总和（总 Allred 评分：0-8），并作为肿瘤中 p21 标记指数。ROC 曲线分析用于确定最佳 p21 评分截断值（4 或>），Fisher 确切检验用于比较肿瘤 p21 评分、传统预后标准和肝转移之间的关系。

结果

对于 PET/PECA 患者，平均年龄分别为 55.6 岁（27-73 岁）和 49.3 岁（28-71 岁），男女比例分别为 7/11 和 7/6。MP-PECAs 的平均 p21 标记指数（%）为 24%（范围=3-63%），而 NMP-PETs 为 9%（范围=1-25%）（p=0.022）。MP-PECAs 的平均 p21 指数（24%）明显高于 PIs（7%）（p=0.0047）。使用 p21 Allred 评分≥4，高 p21 IHC 评分与肝转移的存在具有很强的相关性（p 值<0.001）。高肿瘤 p21 IHC 评分的灵敏度为 93%，特异性为 68%，预测准确率为 78%，阳性预测值为 66%，阴性预测值为 94%。