Detection of occult N2 disease with molecular techniques

Lymph node involvement is the most important factor affecting the prognosis and treatment of patients with potentially resectable NSCLC. Radiographic imaging is inadequate to ascertain lymph node involvement accurately. Currently, lymph nodes are histologically examined with standard histopathologic techniques, such as H&E staining; however, lymph node micrometastases (occult N2 disease) may be missed, leading to inaccurate staging and suboptimal treatment. More accurate strategies, using molecular biologic techniques, are currently being studied. IHC using antibodies to cytokeratins improves the sensitivity of lymph node assessment. Other techniques, such as RT-PCR, may be superior to IHC, and the detection of various cancer-specific gene transcripts by RT-PCR is being evaluated. Many transcripts with high sensitivity also demonstrate low specificity, either because of their presence in non-neoplastic tissue or (as is the case of CK-19) because of the existence of associated pseudogenes. At the present time, the most promising molecular detector may be KS1/4, which is infrequently present in noncancerous cells but has a high sensitivity in metastatic nodes. Genomic analysis of lymph nodes, which may be used to improve the detection of micrometastases and to improve risk stratification, is currently being studied. Genomic signatures have the potential to guide therapeutic decision making as well.