Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.
New three-tier Smad4 immunohistochemical classification predicts SMAD4 mutations better than traditional methods
Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.
Mutations in four major driver genes- KRAS, CDKN2A, TP53, and SMAD4 -are central to the pathogenesis of pancreatic ductal adenocarcinoma (pancreatic ductal adenocarcinoma) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment.
We retrospectively enrolled 63 pancreatic ductal adenocarcinoma patients and systematically characterized the typical immunohistochemical expression patterns of p53 and Smad4.
new intermediate-category scheme correctly predicts SMAD4 mutation status in most cases
Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4 , missense mutations constituted the most frequent variant type.
Using next-generation sequencing as the reference standard, we validated the diagnostic utility of a three-tiered p53 immunohistochemical classification system, particularly in fine-needle biopsy (fine-needle biopsy) specimens.
Our study highlights the complementary diagnostic value of p53 and Smad4 immunohistochemical relative to molecular testing in pancreatic ductal adenocarcinoma, especially when tissue is limited, as commonly encountered in fine-needle biopsy specimens.
The newly established Smad4 immunohistochemical classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.