RESUMO
OBJECTIVES: The prevalence of distant metastasis and second primary tumors is increasing with improved locoregional control in patients with head and neck squamous cell carcinoma. Traditionally, clinicopathologic evidence has been the gold standard used to distinguish distant metastasis from second primary tumors. We report a case in which loss of heterozygosity testing was used to clarify the clonal relationship between the 2 sites of head and neck squamous cell carcinoma. METHODS: A patient with squamous cell carcinoma in the larynx and mandible underwent loss of heterozygosity testing. RESULTS: The loss of heterozygosity testing confirmed that the mandibular cancer was a metastatic presentation of the laryngeal squamous cell carcinoma. CONCLUSIONS: We conclude that loss of heterozygosity testing can be useful in differentiating distant metastasis from second primary cancers in patients with 2 sites of head and neck squamous cell carcinoma, consequently providing important prognostic and staging information.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Perda de Heterozigosidade/genética , Neoplasias Mandibulares/genética , Neoplasias Mandibulares/secundário , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Marcadores Genéticos , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Segunda Neoplasia Primária , Tomografia Computadorizada por Raios XRESUMO
Amyloid precursor protein (APP) has been implicated in squamous cell carcinoma. In this study we show that forced expression of the transcription factor activating protein 2alpha (AP-2alpha) results in significantly increased steady state levels of APP mRNA in human keratinocytes. Sequence analysis of the 5' end of the human APP gene revealed five putative binding sites for AP-2, suggesting that APP is a direct target for transactivation by AP-2. AP-2 protein bound at least 3 of these putative promoter elements in vitro as determined by electrophoretic mobility shift assay. Chromatin immunoprecipitation (ChIP) analysis showed that these binding sites were occupied by AP-2 in cells, thus indicating the relevance to AP-2 binding in vivo. We then analyzed APP and AP-2 mRNA and protein expression in squamous cell carcinoma tumor samples. Analysis of RNA extracted from human tissue showed a significant positive correlation between AP-2alpha and APP mRNA expression. Immunohistochemical staining of tumor samples also demonstrated a positive correlation which was substantiated through western blot studies. Taken together, these findings demonstrate a role for the transcription factor AP-2alpha in the regulation of APP gene expression in human keratinocytes.
Assuntos
Precursor de Proteína beta-Amiloide/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/genética , Receptores de Superfície Celular/genética , Fator de Transcrição AP-2/genética , Fator de Transcrição AP-2/fisiologia , Transcrição Gênica , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Cromatina/genética , Primers do DNA , Humanos , Queratinócitos/fisiologia , Neoplasias Bucais/patologia , Nexinas de Proteases , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
CONTEXT: Differential expression of cell cycle-associated proteins may correlate with human papillomavirus status and may help delineate degree of dysplasia in upper aerodigestive tract squamous lesions. OBJECTIVE: To determine intraepithelial height of immunohistochemical staining for p16, p53, pRb, and Ki-67 in upper aerodigestive tract lesions with reference to degree of dysplasia. Human papillomavirus status was ascertained to correlate with p16 expression. DESIGN: Biopsy specimens of 53 squamous dysplastic and 13 keratotic/hyperplastic lesions were immunohistochemically stained for p16, p53, pRb, and Ki-67. Mean height and proportion of positive staining were quantified and compared for keratotic/hyperplastic, mild, moderate, and severe dysplasia/carcinoma in situ. DNA extracted from paraffin-embedded blocks was evaluated for human papillomavirus by polymerase chain reaction amplification using consensus primers for mucosal viral types. RESULTS: Height of Ki-67 staining within the epithelium increased significantly between mild and moderate and between mild and severe dysplasia, with a trend toward increasing height between moderate and severe dysplasia. The percentage of cases with p16 staining decreased significantly with increasing degree of dysplasia; however, no significant trend in staining height or proportion was observed with p16, p53, or pRb in relation to degree of dysplasia, or between dysplastic and keratotic/hyperplastic lesions. Only 1 of 53 dysplastic lesions was positive for human papillomavirus. CONCLUSIONS: This series of upper airway dysplastic mucosal lesions demonstrated a positive correlation between intraepithelial Ki-67 staining height and degree of dysplasia, offering a diagnostic aid in delineating degree of dysplasia in difficult squamous lesions.
