RESUMO
PURPOSE: To analyze the expression of excision repair cross-complementation group 1 (ERCC1) protein in predicting the clinical outcome of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The histologic specimens of 258 patients with Stage III to IVB nonkeratinizing NPC who were treated with radiotherapy alone (Group I) or concurrent-adjuvant chemoradiotherapy (Group II) were retrieved. Immunostaining on ERCC1 protein was performed. The relationship of ERCC1 expression and clinical outcomes was analyzed. RESULTS: The median ERCC1 score (proportion score of positively stained cells times intensity) was 200 (range, 0-300), and ERCC1 expression was defined as high if the score was above the median. In Group I high-score tumor had a statistically lower locoregional failure-free rate (LRFFR) compared with low-score tumor (p < 0.05) but not distant failure-free rate (DFFR) and overall survival (OS). In Group II no statistically differences were noted in LRFFR, DFFR and OS with regard to the ERCC1 expression. Resistance to cisplatin-containing chemotherapy in high-ERCC1 score tumor was not observed in Group II. Interestingly, low-score tumor in Group I achieved similar local and distant control compared with Group II. Multivariate analysis showed that ERCC1 score was an independent prognostic factor in LRFFR (p < 0.05) and approached statistical significance in failure-free survival (p = 0.08) and OS (p = 0.07). Tumor with high ERCC1 score had a 2-fold (95% confidence interval, 1.02-3.85) increased risk of locoregional failure. This may imply an association of ERCC1 expression with the repair of radiation damage. CONCLUSIONS: High ERCC1 expression predicts poor locoregional control in NPC. Chemotherapy response is not affected by ERCC1 expression. Further validation is required.
Assuntos
Proteínas de Ligação a DNA/análise , Endonucleases/análise , Proteínas de Neoplasias/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/química , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Medicina de Precisão , Adulto JovemRESUMO
BACKGROUND: Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials. AIMS: To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications. METHODS: Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry. RESULTS: Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p = 0.423). CONCLUSION: COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.
Assuntos
Neoplasias Nasofaríngeas/química , Prostaglandina-Endoperóxido Sintases/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/irrigação sanguínea , Carcinoma in Situ/química , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/química , Ciclo-Oxigenase 2 , Epitélio/química , Epitélio/patologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica/métodos , Queratinas/metabolismo , Proteínas de Membrana , Microcirculação , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/irrigação sanguínea , Estadiamento de Neoplasias , Peroxidases/metabolismoRESUMO
In order to elucidate the mechanisms of cisplatin (cis-diamminedichloroplatinum; CDDP)-resistant tumor cells, we previously established a CDDP-resistant KB cell line (KBrc cells) from a parental KB cell line derived from epidermoid carcinoma (KB cells). The KBrc cells were resistant to 5 kinds of platinum (Pt) drugs. Intracellular Pt concentrations in KBrc cells were lower than in KB cells. Decrease of intracellular Pt concentrations was one of the CDDP-resistant mechanisms. When we measured changes of intracellular calcium ion concentration ([Ca2+]i) during exposure to high-dose CDDP, a sustained elevation of the [Ca2+]i level was observed in the KB cells. These results suggest that the mechanisms underlying CDDP resistance involve changes in calcium channels and an alteration of calcium homeostasis in the tumor cell line.