MOLECULAR ANALYSIS OF SURGICAL MARGINS WITH EIF4E IN CAN

描述（改编自研究者摘要）：头颈癌治疗的进步并没有改变这种疾病的不良预后。复发率高（50-60%），特别是晚期疾病。标准的治疗方法是手术后进行放疗。然而，病人死于局部和区域性疾病。因此，能够控制局部疾病复发的治疗将对这些患者有很大的好处。完全切除肿瘤的指导是手术边缘的组织学评估。鉴于遗传改变先于表型改变，组织学评估可能不足以预测复发。分子标记可以更好地识别将发生恶性转化的组织。这在头颈部鳞状细胞癌（HNSCC）中尤其如此。组织学上“无肿瘤”手术切缘的4E升高与较高的局部区域复发率相关，似乎是复发的独立预后因素。我们建议进行一项前瞻性研究，使用4E抗体对手术切缘进行免疫组织化学分析，以确定切缘4E升高是否与肿瘤大小、淋巴结状态、分期、分级、肿瘤中4E水平和切缘发育不良程度无关，是复发的预测因子。我们还将确定4E是否与p53呈正相关。在初步研究中，尽管接受了术后放射治疗，边缘4E水平升高的患者仍会复发。因此，进一步的再切除或辅助治疗可能有助于降低4E阳性切缘患者的复发率。4E的过表达是通过VEGF和FGF-2的升高来实现的。因此，4E边缘阳性的患者可能会受益于额外的治疗，包括抗血管生成药物。与其他癌基因不同，4E似乎是一个有希望的标志物，因为它在100%的HNSCC中升高。它也被发现在乳腺癌中过度表达，因此也可能是其他实体肿瘤手术切除的潜在标志。

DESCRIPTION (As Adapted from the Investigator's Abstract): Advances in the treatment of head and neck cancer has not changed the poor outcome of this disease. Recurrent rates are high (50-60%) especially for advanced stage disease. The standard treatment is surgery followed by postoperative radiation. However patients succumb from local and regional disease. Therefore treatment that can control the local disease recurrences will be of great benefit to these patients. Complete excision of cancer is guided by histologic assessment of surgical margins. Given that genetic alterations precede phenotypic changes, histologic assessment may be inadequate in predicting recurrence. Molecular markers may better identify tissue that will undergo malignant transformation. This is especially true in head and neck squamous cell cancers (HNSCC). 4E elevation in histologically "tumor-free" surgical margins has correlated with a higher loco-regional recurrence and appears to be an independent prognostic factor of recurrence. We propose to perform a prospective study, using immuno- histochemical analysis of surgical margins with an antibody to 4E, to determine whether 4E elevation in the margins was a predictor of recurrence, independent of tumor size, nodal status, stage, grade, 4E levels in the tumor and the degree of dysplasia in the margins. WE will also determine id 4E is positively associated with p53. In preliminary studies patients with elevated levels of 4E in the margins recurred in spite of receiving post-operative radiation therapy. Hence further re-excision or adjuvant therapy may be useful in decreasing the recurrence rate of 4E positive margin patients. Overexpression of 4E was accomplished by an elevation in VEGF and FGF-2. Hence patients with 4E positive margins may benefit from additional therapy which could include anti-angiogenic drugs. 4E appears to be a promising marker as it is elevated in a 100% of HNSCC, unlike other oncogenes. It has also been found to be overexpressed in breast cancer and hence may be a potential marker in the surgical excision of other solid tumors as well.