Ann Thorac Surg 1999;68:348
© 1999 The Society of Thoracic Surgeons
Invited Commentary
Jack A. Roth, MDa
a Department of Thoracic and Cardiovascular Surgery The University of Texas M.D. Anderson Cancer Center 1515 Holcombe Blvd, Box 109 Houston, TX 77030-4095, USA
e-mail: jroth{at}mdanderson.org
Invited commentary
One of the most puzzling and troublesome aspects of treating patients with stage I lung cancer is the significant percentage of patients who recur following apparent complete resection of cancer detected at a relatively early stage. Clearly the biology of these tumors is different from other stage I cancers; however, our current staging tools are not precise enough to identify those patients who may well benefit from more aggressive multimodality treatment. Rapid progress in understanding the molecular basis of lung carcinogenesis promises to provide new biomarkers that may improve prognostication. Lee and coworkers from the National Taiwan University Hospital have studied the expression of two tumor suppressor genes that are among the most frequently dysfunctional in human cancer: p53 and Rb (retinoblastoma gene). The normal p53 protein can cause cell cycle arrest and trigger programmed cell (apoptosis) in response to extensive DNA damage. In the majority of human lung cancers, p53 is mutated, so this cannot occur. This mutation is frequently manifest as p53 protein overexpression as the normal protein has a much shorter half-life and stains minimally with antibodies. Many genes converge on Rb to tightly regulate its ability to trigger cell division. In most lung cancers these growth control genes are inactivated and Rb releases transcription factors unchecked.
Lee and coworkers found that overexpression of p53 correlated with a poor prognosis in stage I patients thus suggesting this may be a useful prognostic marker. Rb expression was not predictive of outcome, but this was not surprising given that most Rb mutations occur in small cell lung cancer. Rb expression did inversely correlate with necrosis, suggesting inhibition of rapid cell proliferation by the intact protein. However, immunostaining does not tell us the genotype and others have found that overexpression of p53 does not always correlate with mutations. Only 1% of the tumor cells were required to be stained to call a sample positive in this study, and the authors do not comment on the extent of heterogeneity that was present which would likely influence outcome. Nevertheless, this is a promising approach that is likely to improve our staging system and identify critical targets for therapeutic intervention.
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Significance of P53 and Rb protein expression in surgically treated non-small cell lung cancers
- Yung-Chie Lee, Yih-Leong Chang, Shi-Ping Luh, Jang-Ming Lee, and Jin-Shing Chen
Ann. Thorac. Surg. 1999 68: 343-347.
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