Cyclin D1 expression is predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes.

BACKGROUND: The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control. RESULTS: Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059). CONCLUSIONS: Our study indicates that the expression of cyclin D1 correlates with the presence of occult cervical metastases in head and neck carcinoma patients, thus suggesting that its immunohistochemical evaluation in biopsy samples may be used as an additional tool for identifying patients to be treated with elective neck dissection.

Immunohistochemical and molecular analysis of bax, bcl-2 and p53 genes in laryngeal squamous cell carcinomas.

BACKGROUND: We investigated the role of apoptosis and its potential alterations in laryngeal squamous cell carcinomas (LSCCs) by evaluating bax, bcl-2 and p53 protein expression in 50 cases and by characterising the molecular status of the bax and p53 genes. MATERIAL AND METHODS: p53 and bax gene mutations were investigated by means of PCR/SSCP and direct DNA sequencing, and bax, bcl-2 and p53 protein expression by means of immunohistochemistry. RESULTS: We identified p53 gene mutations in 17/50 cases (34%); p53 expression in 26 of the 50 cases (52%); bcl-2 expression in 5/50 cases (10%); bax expression in 32/47 cases (68%). 18/33 cases with a wild type p53 gene overexpressed p53 protein: 12 cases (approximately 66%) were bax+/bcl-2-. Of the remaining cases without p53 protein expression, seven cases (approximately 47%) were bax+/bcl-2-. CONCLUSIONS: Our observations suggest that the overexpression of p53 may contribute to the repression of bcl-2 and the induction of bax expression in LSCCs. However, the fact that a number of cases not expressing p53 did not present any clear up-regulation of bax or down-regulation of bcl-2 suggests that bcl-2 and bax may be regulated by various mechanisms other than p53.

Cyclin D1 protein expression is related to clinical progression in laryngeal squamous cell carcinomas.

The expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell carcinomas (LSCCs) in order to determine its clinical and prognostic value. Overexpression of cyclin D1 was detected immunohistochemically using DCS6 monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin D1 expression was detected in 22 of the 74 cases investigated (30 per cent), thirteen of which presented nodal metastases (59 per cent); of the patients without any detectable cyclin D1 protein expression, six presented nodal metastases (12 per cent). Cyclin D1 protein expression was found in five per cent of the specimens of normal mucosa, eight per cent of those with low-grade dysplasia and 20 per cent of those with high-grade dysplasia. A statistically significant association was found between cyclin D1 expression and the supraglottic site (p < 0.05), tumour extension (p < 0.001), the presence of lymph node metastases (p < 0.001), and advanced clinical stage (p < 0.001). Cyclin D1 expression analysis is an important tool in the selection of LSCC patients with an aggressive clinical course.