Perinucleolar compartment prevalence is a phenotypic pancancer marker of malignancy.
BACKGROUND
The perinucleolar compartment (PNC) is a subnuclear structure localized at the nucleolar periphery. Previous studies using breast cancer as a model system demonstrated that PNC prevalence (the percentage of cells with 1 or more PNC) increased with disease progression and was associated with poor patient outcomes.


METHODS
To evaluate the validity of developing PNC prevalence as a novel pancancer prognostic marker, the authors investigated whether PNC prevalence was correlated with malignancy in a spectrum of tissue types and evaluated its selective association with malignancy under various experimental conditions.


RESULTS
PNC prevalence was low in primary and immortalized cells and in cell lines derived from hematologic malignancies, but it was heterogeneous in cell lines derived from solid tumors, including those of epithelial and nonepithelial origins. Studies using human myometrial tissue and thyroid cancer cell lines with various levels of malignancy demonstrated a correlation between high PNC prevalence and malignant potential. Furthermore, PNC prevalence corresponded directly to metastatic capacities in a series of well characterized cell lines of the same origin that were selected for various levels of metastatic capacity in a mouse model. Conversely, PNC prevalence was reduced experimentally by over expressing an antimetastatic protein in breast cancer cells. However, PNC prevalence was not associated with traits that were shared by both cancer and normal cells, including proliferation, glycolysis, and differentiation.


CONCLUSIONS
Together, these observations helped to verify that PNC prevalence selectively represents malignancy in a broad spectrum of solid tissue tumors, demonstrating its potential to be developed as a pancancer prognostic marker of malignancy.
Department of Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
John T
JT
Norton
Callie B
CB
Pollock
Chen
C
Wang
Julian C
JC
Schink
J Julie
JJ
Kim
Sui
S
Huang
D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D002466:Cell Nucleolus; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000175:diagnosis* / Q000648:ultrastructure; D010641:Phenotype
D015415:Biomarkers