title: Perinucleolar compartment prevalence has an independent prognostic value for breast cancer.
abstract: The perinucleolar compartment (PNC) is a multicomponent nuclear structure enriched with RNAs transcribed by RNA pol III and RNA binding proteins. Studies in cultured cells showed an association between PNC and transformed phenotype. To evaluate the relationship between structure and malignancy in vivo, we examined PNC prevalence (the percentage of cells containing at least one PNC) in normal and cancerous paraffin-embedded breast tissues using immunohistochemistry against a PNC-associated protein. Five hundred nuclei in the most active area of each sample were scored for PNC prevalence. The results show that PNC prevalence significantly correlates with the progression of breast cancer (by the criteria of staging). PNC prevalence in primary tumors, lymph nodes, and distant metastases shows a stepwise increase from a median of 23% in primary tumors to approximately 100% in distant metastases. In addition, univariate and multivariate (controlling for tumor size and grade) analyses show that early-stage patients with invasive ductal carcinomas containing a higher PNC prevalence have a significantly poorer prognosis. These findings link PNC prevalence with the progression of breast cancer in vivo and suggest that PNC-containing cells have metastatic advantages. These findings also show the potential of PNC prevalence as a prognostic marker for breast cancer.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: Rajesh V
authors.initials: RV
authors.lastname: Kamath
authors.forename: Ann D
authors.initials: AD
authors.lastname: Thor
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Edgerton
authors.forename: Alicja
authors.initials: A
authors.lastname: Slusarczyk
authors.forename: D J
authors.initials: DJ
authors.lastname: Leary
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: E L
authors.initials: EL
authors.lastname: Wiley
authors.forename: B
authors.initials: B
authors.lastname: Jovanovic
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Nayar
authors.forename: P
authors.initials: P
authors.lastname: Kovarik
authors.forename: F
authors.initials: F
authors.lastname: Shi
authors.forename: Sui
authors.initials: S
authors.lastname: Huang
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology*; D002466:Cell Nucleolus / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis