- 作者列表："Kim H","Choi JY","Rah YC","Ahn JC","Kim H","Jeong WJ","Ahn SH
OBJECTIVE:We aimed to identify the prognostic factors in head and neck squamous cell carcinoma (HNSCC) by using gene expression analysis and candidate biomarkers for adjuvant therapy. STUDY DESIGN:Complementary DNA (cDNA) microarray analysis was performed by using samples from 8 patients, who had died as a result of fulminant recurrence shortly after postoperative radiation therapy, and the results were compared with those from patients with HNSCC of similar stage, but without recurrence. Tissue microarray and immunohistochemistry of samples from 69 patients with oral cavity squamous cell carcinoma indicated ErbB3 to be a prognostic marker, and its expression was analyzed in the HNSCC cell lines. Sapitinib was tested as a concurrent inhibitor of EGFR, ErbB2, and ErbB3. In 15 mice, tumor xenograft was implanted at the lateral tongue, and tumor growth was evaluated. RESULTS:ErbB3 overexpression in patients with treatment-resistant HNSCC was associated with relapse-free survival, disease-free survival, and overall survival (P = .018, P = .006, and P = .003, respectively). In the HNSCC cell line, ErbB2 and ErbB3 overexpression was inhibited by postoperative adjuvant therapy with sapitinib, which was also seen to improve survival in an animal model. CONCLUSIONS:ErbB3 overexpression predicts a poor clinical outcome. Sapitinib was shown to be an effective inhibitor in the HNSCC cell line and animal models of cancer but with no statistical significance. Further studies with larger groups are needed to better support these results.
目的: 我们旨在通过基因表达分析和辅助治疗的候选生物标志物来确定头颈部鳞状细胞癌 (HNSCC) 的预后因素。 研究设计: 使用来自 8 例患者的样本进行互补 DNA (cDNA) 微阵列分析，这些患者在术后放射治疗后不久因暴发性复发而死亡,并将结果与分期相似但无复发的 HNSCC 患者进行比较。69 例口腔鳞状细胞癌患者样本的组织芯片和免疫组织化学表明 ErbB3 是预后标志物，并分析其在 HNSCC 细胞系中的表达。Sapitinib 作为 EGFR 、 ErbB2 和 erbb3 的并发抑制剂进行了测试。在 15 只小鼠中，在舌外侧植入肿瘤异种移植物，并评估肿瘤生长。 结果: ErbB3 在难治性 HNSCC 患者中的过表达与无复发生存期、无病生存期和总生存期相关 (P = .018，P =。006，且 P =。003，分别)。在 HNSCC 细胞系中，术后使用 sapitinib 辅助治疗可抑制 ErbB2 和 ErbB3 过表达，这也可改善动物模型的生存率。 结论: ErbB3 过表达预示临床预后较差。Sapitinib 在 HNSCC 细胞系和癌症动物模型中被证明是一种有效的抑制剂，但无统计学意义。需要更大群体的进一步研究来更好地支持这些结果。
METHODS:INTRODUCTION:Human papillomavirus (HPV) is the most common sexually transmitted infection and is associated with several types of cancer. The number of cases of HPV-associated head and neck squamous cell carcinomas (HNSCCs), especially oropharyngeal carcinomas, has increased significantly in recent years despite decreased tobacco smoking rates. Currently, no data concerning the risk factors and prevalence of HPV in HNSCC patients in all regions of Brazil are available, making it difficult to promote advances in this field of public health. Therefore, our goal is to determine the impact of infection by HPV, including HPVs with different genotypes, on head and neck cancer and the risk factors associated with the development of head and neck cancer in all regions of Brazil. METHODS AND ANALYSIS:This is a case-control study that will include 622 patients and 622 controls from all regions of Brazil. A questionnaire will be applied to gather information on sociodemographic, behavioural and health factors. Oral, cervical or penile/scrotal, and anal specimens and serum samples will be collected from all participants. Formalin-fixed paraffin-embedded tissue from tumour biopsies will be analysed only in the case group. Molecular and serological analyses will be performed to evaluate the presence and role of HPV in the development of head and neck cancer. ETHICS AND DISSEMINATION:This project was approved by the research ethical committee of the proposing institution (Hospital Moinhos de Vento, number 2.852.060). Ethical approval from the collaborators is currently under evaluation and is not yet complete. The results of this study will be presented at meetings with the Brazilian Ministry of Health through technical reports and to the scientific community at national and international events, with subsequent publication of scientific articles.
METHODS:BACKGROUND:Factors related to head and neck cancer and the treatment of the disease can affect quality of life. The aim of this study was to determine factors associated with the severity of impact on oral health-related quality of life (OHRQoL) in survivors of head and neck cancer using a multivariate analysis. METHODS:This cross-sectional study evaluated 90 volunteers who had completed radiotherapy at least 3 months earlier. OHRQoL was assessed using oral health impact profile (OHIP-14) and the data were analyzed using robust variance poisson regression models. RESULTS:The mean total OHIP-14 score was 23.98 ± 12.55. Patients with hyposalivation had 56% higher (worse) mean OHIP-14 total scores (CI:1.11-2.18) and patients with advanced stage tumors had 31% higher mean OHIP-14 total scores (CI:1.03-1.66) in multivariate analyses. CONCLUSION:OHRQoL of survivors of head and neck cancer experienced a negative impact following radiotherapy. The impact was associated with hyposalivation and advanced stage tumors.
METHODS:BACKGROUND:To immunohistochemically evaluate the association between the presence of cancer-associated fibroblasts (CAFs) and the tumour expression of podoplanin (PDPN) in head and neck squamous cell carcinoma (HNSCC) and their association with clinicopathological variables. MATERIAL AND METHODS:A tissue microarray (TMA) with biopsy sections from patients diagnosed with HNSCC was stained with antibodies against the CAFs marker, α-smooth muscle actin (α-SMA), and PDPN. We subsequently evaluated their expression to determine the association between them and with clinicopathological variables including age, primary tumour site, TNM stage, and tumour differentiation grade. RESULTS:Positive reaction to α-SMA was observed in the tumour stroma, revealing spindle-shaped cells compatible with CAFs, which showed a high expression in 62% of cases and a significant association with laryngeal carcinomas, advanced clinical stages, and lower tumour differentiation (P ≤ 0.05). PDPN staining on tumour cells showed low expression in 72% of cases, and it was not associated with any clinicopathological variable or with the presence of CAFs. CONCLUSIONS:The presence of CAFs in the tumour stroma is related to an aggressive phenotype and could increase as the disease progresses, although based on our findings, it would have no relationship, at least directly, with the expression of PDPN.