Ann Thorac Surg 2007;83:221-222
© 2007 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Invited commentary
Thomas D’Amico, MD
Department of Surgery, Duke University Medical Center, Box 3496, Duke South Room 3589, Durham, NC 27710
(Email: damic001{at}mc.duke.edu).
The use of molecular techniques in the staging of malignancy (ie, molecular biologic substaging) may improve the assessment of prognosis and the assignment of therapy for patients with nonsmall cell lung cancer (NSCLC). The current staging system tends to under-stage patients, and clinical staging is even less accurate than pathologic staging. Molecular biologic substaging may be applied to the primary tumor to assess prognosis or chemoresistance, and to lymph nodes, serum, or bone marrow to assess occult systemic metastases.
If it were possible to identify which patients with lung cancer will have systemic recurrence develop prior to the development of clinical or radiographic evidence, systemic therapy may be more effective in improving the outcomes of patients after resection. Molecular analysis of the primary tumor has demonstrated the ability to identify patients with increased risk of recurrence after resection for NSCLC, although this technology has not yet been investigated in phase III clinical trials, and clinical efficacy has not yet been proven. Tumor-related proteins may be secreted into the peripheral circulation of patients with cancer and are detectable by protein analysis. The measurement of serum proteins involved in the pathophysiology of invasion and metastases may be effective in providing prognostic stratification and allowing earlier therapeutic intervention.
The use of serum markers has not yet reached acceptance in assessing prognosis or assigning therapy after complete resection for NSCLC. In 1997 the American Thoracic Society and The European Respiratory Society jointly published guidelines for assessment of NSCLC, indicating that no serum tumor markers had sensitivity and specificity sufficient to reliably detect occult disease or influence treatment. Most tumor proteins are elevated in a minority of patients prior to resection; using a panel of markers may allow a majority of patients to be eligible for surveillance.
Although prognostic information may be attained from initial serum titers of tumor markers, these markers continue to be secreted into the peripheral circulation of patients with continued and recurrent disease. The use of serial serum determinations enables analysis of protein expression within time, and changes in protein levels may be more important than the absolute value of the protein. However, tumor proteins in the serum may be detectable prior to the point at which a recurrent tumor can be identified with conventional radiographic techniques; recently this has been demonstrated. The authors are to be commended for this important study [1]. Molecular biologic substaging of patients with early stage NSLCL using proteomic and genomic strategies should be investigated to improve the accuracy of the TNM staging system to assess prognosis, to identify patients who may benefit from adjuvant therapy, and to predict recurrence.
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- Mizuguchi S, Nishiyama N, Iwata T, et al. Clinical value of serum cytokeratin 19 fragment and Sialyl-Lewis X in non-small cell lung cancer Ann Thorac Surg 2007;83:216-222.[Abstract/Free Full Text]
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