褪色的守护者:TP53空突变在高级别浆液性卵巢癌中的临床相关性。
The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers.
发表日期:2023
作者:
Chiara M Biatta, Michele Paudice, Marco Greppi, Veronica Parrella, Alessia Parodi, Giuseppa De Luca, Gianna Maria Cerruti, Serafina Mammoliti, Cinzia Caroti, Paola Menichini, Gilberto Fronza, Silvia Pesce, Emanuela Marcenaro, Valerio G Vellone
来源:
Frontiers in Immunology
摘要:
我们评估了一系列高级别浆液性卵巢癌(HGSOC)中免疫组化p53染色和TP53基因突变之间的一致性。此外,我们还寻找了p53过度表达和缺失表达组之间的预后差异。包括受HGSOC影响的患者,对每个病例进行了p53免疫组化染色和分子检测(Sanger测序)。进行Kaplan-Meier生存分析以确定TP53突变类型或p53染色模式是否影响总生存率(OS)和无进展生存率(PFS)。共考虑了34例HGSOC。所有免疫组化p53表达为零的病例(n=16)显示了TP53基因突变(n=9个无义突变,n=4个内移缺失突变,n=2个剪接突变,n=1个内移插入突变)。18例p53过度表达的病例中有16例显示了TP53基因错义突变。共有33例病例的随访数据可用(中位随访时间15个月)。我们观察到p53表达为空组的OS显著降低(HR = 3.64,95% CI 1.01-13.16)。免疫组化检测是大多数情况下TP53基因突变的可靠替代方法。尽管研究人群规模较小且中位随访时间有限,我们可以推断,携带p53基因空突变的HGSOC是一个更具侵袭性的亚组。版权所有© 2023 Biatta, Paudice, Greppi, Parrella, Parodi, De Luca, Cerruti, Mammoliti, Caroti, Menichini, Fronza, Pesce, Marcenaro和Vellone。
we evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups.patients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS).34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16].immunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup.Copyright © 2023 Biatta, Paudice, Greppi, Parrella, Parodi, De Luca, Cerruti, Mammoliti, Caroti, Menichini, Fronza, Pesce, Marcenaro and Vellone.