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ITALIAN JOURNAL OF MAXILLOFACIAL SURGERY
A Journal on Maxillofacial Surgery
Official Journal of the Italian Society of Maxillofacial Surgery
Rivista Italiana di Chirurgia Maxillo-Facciale 2001 April;12(1):37-47
Expression of cell cycle regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA in malignant salivary gland tumors. Prognostic implications
Claudio P. P. 1,2, Zamparelli A. 1,2, Califano L. 1, Zupi A., Bellan C. 2,3, Minimo C. 2, Howard C. M. 2, Carrillo G. 4, Micheli P. 5, Cinti C. 2,6, Leoncini L. 3, Giardino C. 1, Giordano A. 2
From the 1 Dipartimento di Scienze Odontostomatologiche e Maxillo-Facciali, Università degli Studi di Napoli «Federico II», Napoli, Italy
2 Department of Pathology, Anatomy and Cell Biology Thomas Jefferson University, Philadelphia, USA
3 Istituto di Anatomia e Istologia Patologica Università di Siena, Siena, Italy
4 Servizio di Anatomia Patologica e Citopatologia Diagnostica, Ospedale «Cardarelli», Napoli, Italy
5 Servizio di Anatomia ed Istologia Patologica, Azienda Ospedaliera «Cotugno», Napoli, Italy
6 Institute of Normal and Pathological Cytomorphology CNR, Bologna, Italy
Background. The retinoblastoma (Rb) family consists of the nuclear tumor suppressor phosphoprotein pRb/p105 and related proteins p107 and pRb2/p130. The involvement of cell cycle regulatory proteins in head and neck tumors has been the subject of numerous investigations. Recent studies on proteins of the retinoblastoma family in oral carcinomas as well as in Burkitt lymphomas and nasopharyngeal carcinomas, showed a direct involvement of pRb2/p130 in the tumorigenesis of the head and neck district. Moreover, we described in a previous report a prevailing nuclear exclusion of pRb2/p130 in lymphoid tumors depending on the presence of mutations that affect the nuclear localization signal (NLS) of pRb2/p130. Extending the studies on head and neck tumors we investigated a group of salivary glands, which would provide a broader perspective on such matter.
Methods. We studied the expression of pRb2/p130, p107, E2F4, p27 and pCNA by immunohistochemistry in a panel of 22 malignant salivary gland tumors.
Results. We have found an inverse correlation between the nuclear expression of pRb2/p130 and tumor grading (degree of malignant potential) and the presence of metastasis that was highly statistically significant (p<0.001). Additionally, decreased nuclear pRb2/p130 expression was significantly associated with a decreased probability of survival (p<0.001). Interestingly, p107 showed a strong direct correlation when compared to the same parameters. pRb2/p130 (p<0.0001) showed the highest percentage of undetectable levels in all the specimens examined and the closest inverse correlation (p<0.0001) with both the histological grading and pCNA expression in the most aggressive tumor types. Additionally, E2F4 showed an identical localization pattern to pRb2/p130.
Conclusions. These data propose an important role for pRb2/p130 in the pathogenesis and progression of certain salivary gland cancers suggesting that pRb2/p130 may be considered a new prognostic marker for salivary gland neoplasms.