title: Expression of bcl-2 in oral squamous cell carcinoma: an immunohistochemical study of 90 cases with clinico-pathological correlations.
abstract: Apoptosis is a genetically determined process playing an active role in tissue size regulation, morphogenesis and removing damaged cells that could be potentially dangerous for their host. Several agents involved in apoptosis regulation, such as the bcl-2 family components, act as oncogenes and are involved in oral carcinogenesis. Aim of this study is to explore bcl-2 immunoreactivity in oral cancers and to assess its potential clinico-pathological implications. Ninety oral squamous cell carcinoma and 10 normal mucosal formalin-fixed, paraffin-embedded samples were analysed for bcl-2 expression by immunohistochemistry. Normal oral mucosa showed a cytoplasmic pattern of bcl-2 immunoreactivity in the basal cell layers. Seventy-four cases of carcinoma (83%) showed no immunoreactivity, at variance with 16 cases (17%) manifesting consistent cytoplasmic positivity. Overall, the peripheral cells of differentiating epithelial tumour islands were intensely stained, with decreasing immunoreactivity toward the centre of the neoplastic nests. Fully keratinised tumour cells showed inconspicuous or absent bcl-2 immunoreactivity. No statistically significant correlations could be demonstrated between bcl-2 immunoreactivity and the sex of the patients, tumour size and with the occurrence of lymph node metastases. Though a direct correlation was found between bcl-2 immunoreactivity and increasing tumour stage, this did not reach statistical significance. Furthermore, G1 and G3 tumours displayed higher percentages of bcl-2-positive cells in comparison with G2 neoplasms and the different distribution of bcl-2 immunoreactivity in G2 and G3 was statistically significant (p<0.05). Finally, patients with absent or low (scores 0 and 1) bcl-2 immunoreactive tumours manifested poorer overall survival rates in comparison with patients with moderate or high (scores 2 and 3) bcl-2 immunoreactive tumours but the difference was not statistically significant. In normal oral mucosa bcl-2 protein is selectively present in the basal cell layers and possibly participates in the control of the terminal keratinocytes differentiation. The study of bcl-2 immunoreactivity possibly may be useful for better characterising and predicting the prognosis of oral SCC but cooperative studies are needed to assess its applications in the clinical practice.
authors.affiliation: Institute of Dental Sciences, Faculty of Medicine, University of Ancona, Italy. lomuziol@tin.it
authors.forename: L
authors.initials: L
authors.lastname: Lo Muzio
authors.forename: M D
authors.initials: MD
authors.lastname: Mignogna
authors.forename: G
authors.initials: G
authors.lastname: Pannone
authors.forename: C
authors.initials: C
authors.lastname: Rubini
authors.forename: R
authors.initials: R
authors.lastname: Grassi
authors.forename: P F
authors.initials: PF
authors.lastname: Nocini
authors.forename: F
authors.initials: F
authors.lastname: Ferrari
authors.forename: R
authors.initials: R
authors.lastname: Serpico
authors.forename: G
authors.initials: G
authors.lastname: Favia
authors.forename: G
authors.initials: G
authors.lastname: De Rosa
authors.forename: E
authors.initials: E
authors.lastname: Maiorano
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2