ORIGINAL ARTICLES   

Rivista Italiana di Chirurgia Maxillo-Facciale 2001 April;12(1):37-47

Copyright © 2002 EDIZIONI MINERVA MEDICA

language: English

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.