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Ann Thorac Surg 1997;64:953
© 1997 The Society of Thoracic Surgeons


Discussion

Discussion

See also page 949.

DR G. ALEXANDER PATTERSON (St. Louis, MO): What do you think is the stimulus for downregulation or lack of expression? Is it some circulating growth factor that comes from somewhere else, or is there something deficient in the way integrin molecules are produced in those tumors? Can you make any speculation?

DR SMYTHE:The answer to that very good question is an important one. It is important to realize that immunohistochemical staining of tumors only allows you to see what is going on at the cell surface. There are a number of steps that could be involved in downregulation of adhesion molecules in tumors, from transcription of a gene to packaging and posttranslational tailoring of the protein, or a protein that originally is expressed may be brought back within the tumor cell at some point. In short, the answer to your question is unclear and is going to require more study to determine.

One hint in regard to why this particular integrin may be downregulated is that, conversely, {alpha}V integrin, in its heterodimeric association with ß3, has been shown to correlate with tumor angiogenesis and aggressiveness in melanoma. However, in one study, it was shown that concomitant with that, {alpha}Vß5 was downregulated. It may well have something to do with angiogenesis in regard to the cause and effect of poor prognosis.

DR PATTERSON:Can you tie this work into the work that David Harpole just published recently regarding angiogenesis (ie, more angiogenesis means a poorer prognosis for the patient)?

DR SMYTHE:I think that has been shown clearly with other tumor types, for instance, carcinoma of the breast. In addition, there have been other reports of a similar nature for several other epithelial tumors.

The hope is that efforts to identify a number of markers such as this and elevated hepatocyte growth factor will be successful. One would then be able to take a series of these markers, as is done in breast carcinoma, and identify patients at particular risk who could benefit from additional therapy.


Related Article

Loss of {alpha}v Integrin Expression and Recurrence in Node-Negative Lung Carcinoma
W. Roy Smythe, Dahlia Wasfi, Joseph E. Bavaria, Steven M. Albelda, and Larry R. Kaiser
Ann. Thorac. Surg. 1997 64: 949-953. [Abstract] [Full Text]




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