Ann Thorac Surg 2003;76:1673
© 2003 The Society of Thoracic Surgeons
Original article: general thoracic
Invited commentary
Joseph Rubin, MD, CMa
a 22 River Reach Way, Charleston, SC 29407-3372, USA
e-mail: jrubin{at}knology.net
Doctor Watanabe and colleagues have introduced a simple, innovative scheme for diagnosing lung cancer that should serve as a departure point for developing a new paradigm for early detection. Although the study was based on a small sample—12 people with adenocarcinoma in peripheral nodules ranging from 8 mm to 28 mm in diameter—the authors were able to demonstrate that CYFRA and CEA marked the malignant nodules even when routine sputum cytology failed. Because of the small study group, the practicing community must regard the findings as preliminary, awaiting further confirmation and development. As the authors point out, the bronchoscopic microsampling probe in its present iteration has its physical limitations; ie, it cannot bend around sharp corners. Nevertheless, the authors' concept opens the way for clinicians to apply protein profiling at the molecular level for accurate and early detection of lung cancer other than adenocarcinoma, potentially eliminating more risky invasive procedures now commonly used to distinguish benign from malignant nodules.
Tumor markers from bronchoalveolar lavage and serum are notoriously insensitive in detecting lung cancer. The authors hypothesized that markers released from small, peripheral malignancies of the lung would be diluted away in epithelial lining fluid (ELF) to levels indistinguishable from background concentrations. They conceived that their microsampling probe would soak up small samples of ELF near the peripheral nodule during bronchoscopy. They noted that there were, in fact, significantly higher concentrations of CYFRA and CEA in ELF next to peripheral adenocarcinomas, compared to levels detected in ELF retrieved from contralateral lung of the same subject and the lungs of individuals who did not have cancer. SLX, the third marker tested, was not expressed in the adenocarcinomas of their study sample.
Novel molecular technologies that can identify cellular changes at the level of the genome or proteome have revitalized early-detection research [1]. Sophisticated data analysis has demonstrated that gene expression patterns distinguish multiple tumor types. The authors' method opens the way to enlarge an existing database of protein expression that is a resource for biomarker identification in lung cancer and other types of cancer. The database integrates two-dimensional gel profiles, mass spectrometry data, quantitative protein data, and gene expression data at the RNA level [2]. These analyses have led to the detection of new tumor markers and markers of tumor progression. Gene expression arrays are also capable of predicting the survival of patients with various malignancies including lung cancer [3]. The authors have bridged a gap between clinical and theoretical, an advance that should enhance early detection as well as therapy of lung cancer.
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- Hanash S., Brichory F., Beer D. A proteomic approach to the identification of lung cancer markers. Dis Markers 2001;17:295-300.[Medline]
- Etzioni R., Urban N., Ramsey S., et al. The case for early detection. Nat Rev Cancer 2003;3:243-252.[Medline]
- Yeatman T.J. The future of clinical cancer management: one tumor, one chip. Am Surg 2003;69:41-44.[Medline]
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