HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Survivin phosphorylation and M-phase promoting factor in oral carcinogenesis

G. Pannone1, P. Bufo1, R. Serpico2, C. Rubini3, R. Zamparese1, F. Corsi1, M.C. Pedicillo1, G. Pannone1, S. Staibano4, G. De Rosa4 and L. Lo Muzio1

1Department of Surgical Science - Section of Pathology - University of Foggia, Foggia, Italy, 2Department of Oral Pathology, Second University of Naples, Naples, Italy, 3Institute of Pathology - University of Ancona, Ancona, Italy and 4Department of Biomorphological and Functional Science - Section of Pathology - University of Naples “Federico II”, Naples, Italy

Offprint requests to: Prof Lorenzo Lo Muzio, Via Carelli, 28, 71100 Foggia, Italy. e-mail: lomuziol@tin.it or llomuzio@tin.it


Summary. Survivin is a recently described inhibitor of apoptosis and mitotic regulator which is selectively over-expressed in human tumors. Its expression rate is predictive of disease progression, early recurrences and resistance to therapy. Up-regulation of survivin in oral pre-malignant lesions (OPL) and in oral squamous cell carcinoma (OSCC) has already been demonstrated in previous studies. A critical step for activation of survivin has been identified in the phosphorylation on Thr34 by the main mitotic kinase p34cdc2–cyclin B1. The aim of this work was to investigate the relationship between survivin, its phosphorylated active form (p-survivin) and M-phase promoting factor (MPF), p34cdc2-cyclin B1 in oral carcinogenesis. 32 OSCCs and 17 OPLs from surgical specimens were studied for cyclin B1, p-survivin, survivin, and p34cdc2 expression by immunohistochemistry. All cases of OSCC expressed survivin and its expression rate was correlated to p-survivin levels (P<0.05). Cyclin B1 was positive in 80% of cases, while p-34cdc2 was over-expressed in all OSCCs. All OPLs associated with OSCC expressed survivin and its levels were correlated to p-survivin levels (P<0.05). Cyclin B1 was positive in 70% of cases, while p-34cdc2 was positive in all OPLs. In conclusion, this study demonstrated that MPF, survivin and p-survivin are expressed during early and late phase of oral carcinogenesis. MPF proteins, which are co-expressed on mitotic apparatus, could represent a potential target for therapies based on manipulation of survivin phosphorylation, which would induce apoptosis in cancer cells. Histol Histopathol 22, 1241-1249 (2007)

Key words: OSCC, Survivin, p34cdc2, Cyclin-B1, p-survivin, Apoptosis, MPF

DOI: 10.14670/HH-22.1241