Speakers - CWC 2023

Abstract

The perinucleolar compartment (PNC) is a recently identified subnuclear structure found in the periphery of the nucleolus of malignant tumor cells. It is enriched with RNA polymerases and RNA-binding proteins. PNC is not found in normal healthy cells and becomes prevalent in cancers, particularly in metastatic tumors suggesting that it reflects the metastatic potential of cancer cells. PNC has been identified in several cancers, and its prevalence was noted to be associated with worse clinical parameters in ovarian, colorectal, and breast cancers. PCN is not present in normal healthy cells, and thus it is an ideal target for novel anticancer drugs. Metarrestin inhibits PNC assembly and thus could disrupt cellular processes that are crucial in maintaining malignant phenotype. The principal PNC components include RNA and proteins.  The polypyrimidine tract binding protein (PTB) is one of the integral PNC protein components. Detection of PTB by immunohistochemistry in tumor tissues serves as a biomarker for the presence of this structure.  We have recently studied pediatric Ewing’s sarcoma tumor cases, from Caucasian and Hispanic patients, for PNC prevalence by immunohistochemical detection of the polypyrimidine tract binding protein. EWS cases showed staining ranging from 0-100% that was categorized as diffuse (≥77%, n=9, high PNC) or not diffuse (<77%, n=31). High PNC prevalence was significantly higher in Hispanic patients from the US (n= 6, p=0.017) and in patients who relapsed with metastatic disease (n=4; p=0.011). High PNC was associated with significantly shorter disease-free survival and early recurrence compared to those with low PNC. In conclusion, this study has demonstrated the presence of PNC in EWS, reflecting its utility as a predictive biomarker associated with tumor metastasis, specific microRNA profile, Hispanic ethnic origin, and poor prognosis. Additional studies on other pediatric sarcomas for PNC prevalence and association with patients’ outcomes will be highly welcome.