Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cancer Center, Union Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
BMC Cancer. 2023 Oct 19;23(1):1008. doi: 10.1186/s12885-023-11513-x.
To clarify the relationship between p53 immunohistochemistry (IHC) staining and TP53 alterations (including mutations and deletions) in large B-cell lymphomas (LBCLs) and to explore the possibility of p53 IHC expression patterns as surrogate markers for TP53 alterations.
A total of 95 patients diagnosed with LBCLs were selected, and paraffin samples were taken for TP53 gene sequencing, fluorescence in situ hybridization and p53 IHC staining. The results were interpreted by experienced pathologists and molecular pathologists.
Forty-three nonsynonymous TP53 mutations and p53 deletions were detected in 40 cases, whereas the remaining 55 cases had wild-type TP53 genes. The majority of TP53 mutations (34/43, 79.1%) occurred in exons 4-8, and R248Q was the most common mutation codon (4/43, 9.3%). The highest frequency single nucleotide variant was C > T (43.6%). p53 expression was interpreted as follows: Pattern A: p53 staining was positive in 0%-3% of tumor cells, Pattern B: p53 staining was positive in 4-65% of tumor cells, Pattern C: more than 65% of tumor cells were stained positive for p53. The p53 IHC expression patterns were associated with TP53 alterations. Gain of function variants and wild-type TP53 tended to exhibit type C and B p53 expression patterns, but loss of function variants were exclusively seen in type A cases. Additionally, interpretation of the staining by various observers produced significant reproducibility.
The p53 IHC expression patterns can be used to predict TP53 alterations and are reliable for diverse alteration types, making them possible surrogate biomarkers for TP53 alterations in LBCLs.
为了阐明 p53 免疫组化（IHC）染色与大 B 细胞淋巴瘤（LBCL）中 TP53 改变（包括突变和缺失）之间的关系，并探讨 p53 IHC 表达模式作为 TP53 改变替代标志物的可能性。
选择 95 例诊断为 LBCL 的患者，采集石蜡样本进行 TP53 基因测序、荧光原位杂交和 p53 IHC 染色。由有经验的病理学家和分子病理学家对结果进行解读。
在 40 例中检测到 43 个非同义 TP53 突变和 p53 缺失，而其余 55 例具有野生型 TP53 基因。大多数 TP53 突变（34/43，79.1%）发生在外显子 4-8 中，R248Q 是最常见的突变密码子（4/43，9.3%）。最高频率的单核苷酸变异是 C>T（43.6%）。p53 表达的解读如下：模式 A：肿瘤细胞中 p53 染色阳性率为 0%-3%，模式 B：肿瘤细胞中 p53 染色阳性率为 4%-65%，模式 C：超过 65%的肿瘤细胞染色阳性。p53 IHC 表达模式与 TP53 改变相关。功能获得性变异和野生型 TP53 倾向于表现为 C 型和 B 型 p53 表达模式，而功能丧失性变异仅见于 A 型病例。此外，不同观察者对染色的解读具有显著的可重复性。
p53 IHC 表达模式可用于预测 TP53 改变，并且对各种改变类型具有可靠性，因此可能成为 LBCL 中 TP53 改变的替代生物标志物。
