Performance of Immunohistochemistry to Detect Rb/p53 Alterations in High-Grade Neuroendocrine Neoplasms: Staining...

Area of Science:

• Oncology
• Molecular Pathology
• Cancer Biomarkers

Background:

• Rb and p53 protein status are critical for classifying high-grade neuroendocrine neoplasms (HG-NENs) and predicting platinum-based chemotherapy response.
• Traditional methods for assessing Rb and p53, like next-generation sequencing (NGS), face limitations with formalin-fixed paraffin-embedded (FFPE) samples and detecting small deletions in routine practice.

Purpose of the Study:

• To characterize the immunohistochemical (IHC) staining patterns of Rb, p16, and p53 in a large cohort of well and poorly differentiated lung and pancreatic HG-NENs.
• To compare the performance of Rb/p53 NGS profiling with IHC in detecting molecular alterations within these tumors.

Main Methods:

• Immunohistochemistry (IHC) was used to determine Rb, p16, and p53 protein status in 132 HG-NENs (79 pulmonary, 53 pancreatic).
• Next-generation sequencing (NGS) was performed on a subset of 63 tumors for comparative analysis.
• Three distinct IHC patterns (loss, variable, strong expression) were identified for Rb and p53.

Main Results:

• IHC revealed distinct expression patterns: Rb loss in 45.4%, variable Rb expression in 40.8%, and strong Rb expression in 13.6%. p53 loss was observed in 32.6%, variable p53 in 37.1%, and strong p53 in 30.3%.
• Agreement between NGS and IHC was 76.2% for Rb and 82.5% for p53.
• NGS missed abnormal Rb and p53 IHC profiles in 42% and 20.5% of cases, respectively, highlighting potential underdetection of molecular alterations.

Conclusions:

• Immunohistochemistry (IHC) serves as a reliable, rapid, and cost-effective screening method for assessing Rb and p53 status in HG-NENs.
• IHC is superior to NGS in detecting certain molecular alterations, making it a valuable tool in routine clinical practice for HG-NEN diagnosis and management.