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


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.

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