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Expression of Cell Cycle–Regulated Proteins pRB2/p130, p107, E2F4, p27, and pCNA in Salivary Gland Tumors: Prognostic and Diagnostic Implications

Authors' Affiliations: ¹ Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University; ² Department of Pathology and Laboratory Medicine, College of Medicine, Drexel University, Philadelphia, Pennsylvania; ³ Department of Human Pathology and Oncology, University of Siena, Nuovo Policlinico "Le Scotte", Siena; ⁴ Dipartimento di Medicina di Laboratorio ed Anatomia Patologica, A.O. "Antonio Cardarelli"; and ⁵ Dipartimento di Scienze Odontostomatologiche e Maxillo-Facciali, Universita' degli Studi di Napoli "Federico II", Naples, Italy

Requests for reprints: Pier Paolo Claudio, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Biology-Life Sciences Building, Suite 333, 1900 North 12th Street, Philadelphia, PA 19122-6099. Phone: 215-204-9523; Fax: 215-204-9522; E-mail: claudio{at}temple.edu.

The retinoblastoma family consists of the tumor suppressor nuclear phosphoprotein pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in lung and endometrial cancer and choroidal melanomas show a tight inverse correlation between the histologic grading in the most aggressive tumor types and pRb2/p130 expression. This led us to investigate the role of pRb2/p130 in salivary tumors. We studied the expression of pRb2/p130, p107, E2F4, p27, and PcNA by immunohistochemistry in a panel of 44 salivary gland tumors. We found a direct correlation between the cytoplasmic expression of pRb2/p130 and tumor grading and the presence of metastasis that was highly statistically significant (P < 0.001). Additionally, increased cytoplasmic pRb2/p130 expression was significantly correlated with a decreased probability of survival (P < 0.001). Interestingly, p107 nuclear expression showed a strong direct correlation when compared with the same variables. pRb2/p130 showed the highest percentage of undetectable nuclear levels in the specimens examined and the tightest inverse correlation (P < 0.0001) with both the histologic grading and pCNA expression in malignant salivary tumors. Additionally, E2F4 showed an identical localization pattern as to that of pRb2/p130. These data suggests an important role for pRb2/p130 in the pathogenesis and progression of certain salivary gland cancers.

Key Words: Salivary gland tumors • Retinoblastoma • Cell cycle • Prognostic factor