MOLECULAR ANALYSIS OF SURGICAL MARGINS WITH EIF4E IN CAN

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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.