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Perinucleolar Compartment Prevalence Has an Independent Prognostic Value for Breast Cancer

Departments of ¹ Cell and Molecular Biology, ² Pathology, and ³ Preventive Medicine, Northwestern University Medical School; ⁴ Department of Pathology, John H. Stroger, Jr., Hospital of Cook County, Chicago, Illinois; ⁵ Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and ⁶ Department of Pathology, Sun Yet-Sen University Cancer Center, Guangzhou, People's Republic of China

Request for reprints: Sui Huang, Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Ward Building, 11-240, Chicago, IL 60611. Phone: 312-503-4269; Fax: 312-503-7912. E-mail: s-huang2{at}northwestern.edu.

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 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.

Key Words: Perinucleolar Compartment (PNC) Prevalence • Nuclear Structure • Breast Cancer • Prognosis • Tumor Marker

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