Brain Metastasis in Patients with Non-Small Cell Lung Cancer: Immunohistochemical Markers

Abstract

Lung cancer is the leading cause of cancer death in developed countries. Because of the lack of diagnostic tools for early detection and of efficient treatment for advanced disease, the prognosis of lung cancer is still poor, with 5-year survival estimated at less than 15%. Among patients treated for early non-small cell lung cancer (NSCLC), nearly 40% will relapse within 2 years and die of metastatic disease. To date, histologic features of the lung tumor and clinical factors have been of limited value in predicting patient outcome. Advances in combined modality therapy for lung cancer have resulted in improved local disease control and limited extrathoracic metastatic spread. Recently, several lines of studies investigating the molecular pathways involved in the pathogenesis of lung cancer provided a basis for early detection of NSCLC. Despite these advances, intracranial recurrence rates remain high. Prophylactic cranial irradiation is a therapeutic modality designed to eradicate subclinical central nervous system metastases in order to prevent intracranial relapse, and therefore, increase overall survival. However, many questions regarding the optimal dose, fractionation, and toxicity of prophylactic cranial irradiation remain unanswered. Of particular importance, there are no defined guidelines as to what group or subgroup of patients with NSCLC should be treated. In the last few years, several molecular markers have been investigated as potential predictors of the development of brain metastases. Identification of such markers is particularly needed to identify that group of patients with NSCLC who are at an increased risk of developing brain metastases and, therefore, might benefit from prophylactic brain irradiation. Preliminary studies by our group and others identified certain molecular markers with potential benefits in identifying patients with NSCLC who are at increased risk of developing brain metastases. These results indicated that patients with NSCLC who had high Ki-67 expression, low caspase-3 expression, high vascular endothelial growth factor C expression, and low E-cadherin expression in their tumors are at increased risk of developing brain metastases and may benefit from close clinical surveillance and perhaps prophylactic brain irradiation.