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.
Cancer Genomics Proteomics. 2023 Nov-Dec;20(6):522-530. doi: 10.21873/cgp.20402.
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.
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.
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.
In patients with primary PETs, p21 IHC is superior to conventional criteria in predicting presence or absence of liver metastases.
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。
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。
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%。
在原发性 PETs 患者中，p21 IHC 在预测肝转移的存在或不存在方面优于传统标准。
