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Association Between Promyelocyte Protein and Small Ubiquitin-Like Modifier Protein and the Progression of Cervical Neoplasia

From the Departments of Obstetrics and Gynecology, and Pathology, University Hospital, Zurich, Switzerland, Beckman Laser Institute and Laser Microbeam and Medical Program, and Department of Medicine, Division of Hematology/Oncology, University of California, Irvine, Irvine, California.

Address reprint requests to: Vickie J. LaMorte, PhD, Beckman Laser Institute, 1002 Health Sciences Road East, Irvine, CA 92612; E-mail: lamorte{at}uci.edu.

OBJECTIVE: To examine the association between the size and number of promyelocyte protein-containing nuclear bodies, their colocalization with the small ubiquitin-like modifier protein, and existing histopathologic staging of cervical neoplasia progressing toward squamous cell carcinoma.

METHODS: Fluorescence-based immunodetection of the promyelocyte protein and the small ubiquitin-like modifier protein was performed on paraffin-embedded and histopathologically graded human uterine cervical tissues. Quantitative measurements of the size and number of the promyelocyte protein-containing nuclear bodies were made and statistically analyzed.

RESULTS: We found that promyelocyte protein-containing nuclear bodies exhibit changes in both size and number throughout the continuum of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. An increase in number and size of the bodies occurs with progression from normal to CIN I/CIN II. In CIN III, two new subcategories of nuclear body are present with distinctly different promyelocyte protein patterns, with the type B CIN III losing the small ubiquitin-like modifier protein partnership. In squamous cell carcinoma, we see the loss of this colocalization in both well and poorly differentiated tumors, with a distinctly different promyelocyte protein pattern. Well-differentiated tumors have bigger nuclear bodies that are more numerous than those of the poorly differentiated tumors.

CONCLUSION: These data support the use of promyelocyte and small ubiquitin-like modifier proteins as a cytodiagnostic marker that parallels cervical cancer progression.