[CCND1 gene amplification in the adenoid cystic carcinoma of the minor salivary glands]. / Amplificación del gen de la ciclina D1 en los carcinomas adenoides quísticos de glándulas salivares menores.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumour of epithelial origin that represents the most common malignant neoplasm of the minor salivary glands. However, little is known about the genes involved in the development and progression of this tumour. Cyclin D1 gene (CCND1) plays a key role in the control of the cell cycle, and its amplification is described in numerous cancers. The aim of this study is to determine the amplification of the CCND1 gene in the ACC of the minor salivary glands. MATERIALS AND METHODS: A retrospective study was performed on 12 patients with ACC of the head and neck. The amplification of the CCND1 was determined using multiple PCR. RESULTS: Amplification of the CCND1 was found in 4 patients (33.3%). No correlation was found between CCND1 amplification and clinicopathological parameters, although disease-free survival was diminished in patients with amplification. DISCUSSION/CONCLUSIONS: Our study demonstrates for the first time the amplification of the CCND1 gene in ACC. We have found an amplification rate similar to others neoplasms. CCND1 amplification seems to be associated with a poorer prognosis in these tumours, although this needs to be confirmed in larger studies.

[Epidermal growth factor receptor gene amplification and E-cadherin expression in head and neck carcinomas]. / Amplificación del gen del receptor del factor de crecimiento epidérmico y expresión de la E-cadherina en los carcinomas de cabeza y cuello.

INTRODUCTION: The E-cadherin adhesion molecule is fundamentally involved in the maintenance of normal epithelial morphology and differentiation. The scattering and invasion of cancer cells induced by epidermal growth factor receptor (EGFR) activation has been suggested to be probably by affecting E-cadherin function. The aim of this study is to confirm whether EGFR amplification is related to E-cadherin expression in head and neck squamous cell carcinomas. MATERIAL AND METHODS: Fifty patients with head and neck squamous cell carcinoma were studied. EGFR amplification was analyzed by semiquantitative PCR. E-cadherin expressión was determined by immunohistochemistry. RESULTS: EGFR amplification was found in 9 cases (18%). E-cadherin expression was generally weaker in tumors than in adjacent normal epithelium. No relationship was found between EGFR amplification and E-cadherin expression. CONCLUSION: EGFR amplification did not affect the level of E-cadherin expression, suggesting a complementary role of both of these molecules in reduction of cellular adhesion in head and neck squamous cell carcinomas.

[Inactivation of p53 and amplification of cyclin D1 in squamous cell carcinomas of the head and neck]. / Inactivación de P53 y amplificación de la ciclina D1 en los carcinomas epidermoides de cabeza y cuello.

P53 and CCND1 (cyclin D1) genes play a critical role in the cell cycle regulation. Abnormalities of these genes are frequent in different types of cancers, including those of the head and neck. The aim of this work is to investigate whether P53 inactivation (determined by loss of heterozygosity analysis) is related to CCND1 gene amplification (determined by differential PCR analysis), and if these alterations are correlated with clinical outcome in a series of 56 patients with squamous cell carcinoma of the head and neck. Loss of heterozygosity of the P53 gene was found in 39 cases (70%) and CCND1 amplification in 17 cases (30%). Both abnormalities together were found in 11 cases (20%), without a significant association between them (P = 0.83). No relationship was found between P53 inactivation, the clinico-pathological parameters analyzed and the clinical outcome. CCND1 amplification was associated with advanced T-stages (P = 0.02), nodal metastases (P = 0.01) and a decreased survival (P = 0.002). The combination of both abnormalities shows a pattern that seems to be additive, since it was associated with an increase in tumor recurrences and a decrease in survival that was higher than for either of them individually. In conclusion, P53 and CCND1 abnormalities are frequent in squamous cell carcinomas of the head and neck. The combined analysis of these abnormalities seems to be more informative than either of them individually and may have a prognostic value in these carcinomas.

[Prognostic significance of the expression of adhesion molecules E-cadherin, Cd44s and CD44V6 in supraglottic squamous carcinoma]. / Significado pronóstico de la expresión de las moléculas de adhesión E-cadherina, CD44s y CD44V6 en los carcinomas epidermoides supraglóticos.

OBJECTIVE: To establish the prognostic significance of the expression of adhesion molecules E-cadherin, CD44s and CD44v6 in squamous cell carcinomas of the supraglottic larynx. MATERIAL AND METHODS: The expression of the studied molecules was determined by immunohistochemistry in paraffin-embedded tissue specimens from 101 patients. RESULTS: The expression of the three molecules was reduced in carcinomas compared to normal epithelium. The cases with recurrence showed an E-cadherin and CD44s expression significantly lower than those cases without recurrence. Reduced expression of any of the three molecules correlated with a decrease in survival, although the differences were not significant. In multivariate analysis only nodal stage (N) was an independent prognostic factor. CONCLUSIONS: Although reduced expression of E-cadherin, CD44s and CD44v6 seems to be related to a poor prognosis in supraglottic squamous cell carcinomas, these changes do not offer a useful adjunct to current prognostic indicators.

[CCND1 oncogene amplification and cellular DNA content in squamous cell carcinomas of the head and neck]. / Amplificación del oncogén CCND1 y contenido celular de ADN en los carcinomas epidermoides de cabeza y cuello.

Cyclin D1 protein (encoded by the CCND1 gene) contributes to the progression of the cell cycle in the G1/S checkpoint. Cyclin D1 overexpression (for instance as a consequence of CCND1 amplification) might result in loss of control over genetic damage at this point and in an accumulation of chromosomal aberrations. In this work we analyze whether CCND1 amplification is associated with a higher incidence of alterations in cellular DNA content. 31 squamous cell carcinomas of the head and neck were studied. CCND1 amplification was determined by polymerase chain reaction. Cellular DNA content was determined by flow cytometry. CCND1 amplification was found in 6 (19%) cases. Thirteen (42%) cases were diploid and 18 (58%) were aneuploid. Two (33%) of the 6 cases with CCND1 amplification were aneuploid compared with 16 (64%) of the cases without CCND1 amplification (P = 0.36). We conclude that CCND1 amplification is not associated to a higher incidence of chromosomal aberrations in squamous cell carcinomas of the head and neck.

[Relationship between the integration of human papillomavirus and loss of heterozygosity of the P53 gene in squamous cell carcinomas of the head and neck]. / Asociación entre la integración del virus del papiloma humano y la pérdida de heterozigosidad del gen p53 en los carcinomas epidermoides de cabeza y cuello.

Human papillomavirus integration in cellular DNA and loss of heterozygosity of P53 gene are both related with tumour formation process by promoting genomic instability that leads to DNA abnormalities accumulation. In order to analyze the relationship between both events, 26 squamous cell carcinomas of the head and neck were studied. HPV 16 and 6b DNA was detected by PCR in 8 cases (31%), whereas P53 loss of heterozygosity was present in 16 cases (61%). No correlation was found between both events and they were not related to clinical factors neither the prognosis. Consequently, HPV integration and loss of heterozygosity of P53 seem to act independently in the genesis of these tumours.