Distinctive clinicopathological associations of amplification of the cortactin gene at 11q13 in head and neck squamous cell carcinomas.

Amplification of the 11q13 region is a prevalent genetic alteration in head and neck squamous cell carcinoma (HNSCC). We investigated the clinical significance of cortactin (CTTN) and cyclin D1 (CCND1) amplification in both malignant transformation and tumour progression. CTTN and CCND1 amplification was analysed by differential and real-time PCR in a prospective series of laryngeal/pharyngeal carcinomas and archival premalignant tissues. CTTN mRNA and protein expression were respectively determined by real-time RT-PCR and immunohistochemistry, and correlated with gene status. Molecular alterations were associated with clinicopathological parameters and disease outcome. CTTN and CCND1 amplifications were respectively found in 75 (37%) and 90 (45%) tumours. Both correlated with advanced disease; however, only CTTN amplification was associated with recurrence and reduced disease-specific survival (p = 0.0022). Strikingly, CTTN amplification differentially influenced survival depending on tumour site (p = 0.0001 larynx versus p = 0.68 pharynx) and was an independent predictor of reduced survival in the larynx (p = 0.04). CCND1 amplification was detected in early tumourigenesis and increased with the severity of dysplasia. Importantly, CTTN amplification was only found in high-grade dysplasias that progressed to invasive carcinoma. CTTN gene status strongly correlated with mRNA and protein expression. Furthermore, CTTN overexpression correlated significantly with reduced disease-specific survival (p = 0.018). Taken together, these data indicate that CTTN may serve as a valuable biomarker to identify patients with laryngeal tumours at high risk of recurrence and poor outcome.

Lectin-like transcript 1 (LLT1) expression is associated with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

The interaction of lectin-like transcript 1 (LLT1) with CD161 inhibits Natural Killer cell activation. Overexpression of LLT1 contributes to the immunosuppressive properties of tumor cells. However, there are little data about LLT1 expression in human solid tumors. The objective of this paper is to investigate the relationship between LLT1 expression with the clinicopathologic features and its impact on the prognosis of head and neck cutaneous squamous cell carcinoma (cSCC). LLT1 expression was analyzed on paraffin-embedded tissue samples obtained from 100 patients with cSCC by immunohistochemistry. The estimator of Fine and Gray was used to estimate the cumulative incidence curves for relapse. Proportional Hazard models and Hazard ratios (HRs) were used for studying the risk of tumor relapse and mortality. LLT1 strong expression was a significant risk factor for nodal metastasis with crude and adjusted ratios (HRs) of 3.40 (95% CI 1.39-9.28) and 3.25 (95% CI 1.15-9.16); and for cSCC specific death of 6.17 (95% CI 1.79-21.2) and 6.10 (95% CI 1.45-25.7). Strong LLT1 expression is an independent predictor of nodal metastasis and poor disease-specific survival and it might be helpful for risk stratification of patients with cSCC.

[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.

[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.

[Expression of annexins Al and A2 in the mucosa of the upper airdigestive tract]. / Expresión de las anexinas Al y A2 en la mucosa del tracto aerodigestivo superior.

INTRODUCTION: Annexins A1 and A2 have been related with the maintenance of tissue integrity. They have been identified in a wide variety of tissues, but little is known regarding their expression in upper the aerodigestive tract. The aim of this work is to describe the expression of these proteins in the mucosa of the upper aerodigestive tract. MATERIAL AND METHODS: Tissue samples from respiratory (nasal and laryngeal) and digestive (oral and pharyngeal) mucosa from non-oncological patients were studied. Annexin A1 and A2 expression was determined by immunohistochemistry. RESULTS: Both annexins were expressed in the ciliated and in the stratified non-keratinized epithelia, but with a different pattern; ANXA1 was expressed in the more differentiated cells whereas ANXA2 was expressed in the less differentiated ones (with the exception of the cilia of ciliated cells). CONCLUSION: Although annexins A1 and A2 are structurally and philogenetically related its expression pattern in the upper aerodigestive tract suggests that they have different functions.

[Detection of herpes simplex virus and Epstein-Barr virus in squamous cell carcinoma of the upper airways and digestive system]. / Detección del virus herpes simplex y del virus de Epstein-Barr en los carcinomas de células escamosas de vías aerodigestivas superiores.

OBJECTIVE: Previous studies have investigated the role of viruses in tumor origin of head and neck cancer. Despite this, mechanis of viral carcinogenesis remain unclear. The aim of this study is to determine the prevalence of herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in malignant laryngeal and oropharyngeal lesions. MATERIAL AND METHODS: Fresh frozen specimens of 28 laryngeal and oropharyngeal squamous cell carcinomas were studied. The presence or absence of HSV and EBV was determined with polymerase chain reaction (PCR) assays. RESULTS: None of the samples showed evidence for EBV DNA. One tonsilar carcinoma case (3.5%) was positive for HSV DNA detection. CONCLUSIONS: These results do not support HSV and EBV as etiological factors in head and neck cancer.

[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.

[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.