Ann Thorac Surg 2003;76:218
© 2003 The Society of Thoracic Surgeons
Original article: general thoracic
Invited commentary
James S. Allan, MDa
a Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, 55 Fruit Street, Blake 1570, Boston, MA 02114, USA
e-mail: jallan{at}partners.org
The CD44 receptor is a transmembrane glycoprotein whose principal ligand is hyaluronate. As such, the CD44 receptor plays a significant role in the anchoring of cells to a basement membrane and in the maintenance of epithelial cell polarity. Altered expression of the CD44 receptor (and its splice-variant isoforms) is known to be associated with tumor progression and metastases in a variety of cancers.
Lee and colleagues have now examined CD44 expression in both normal human thymic tissue and in resected thymomas of varying histologic subtypes and clinical stages. Their results show that normal thymic tissue occasionally expresses the CD44 receptor, and typically shows no expression of the CD44v5 and CD44v6 isoforms. In contrast, a significant elevation in the expression of the CD44v5 isoform was observed in the neoplastic cells located in the tumor capsules of thymomas. Moreover; they have demonstrated a positive correlation between CD44v5 expression and the Masaoka stage of the thymomas. Using a proportional hazards model, they have further shown that the increased expression of the CD44v5 isoform is an independent adverse prognosticator in the survival of these patients.
From a mechanistic viewpoint, these data suggest that specific alterations in molecules responsible for the maintenance of epithelial integrity do indeed influence the propensity of a malignancy to metastasize. Ultimately, these altered membrane receptors may prove to be useful targets for the directed delivery of chemotherapeutic or immunomodulatory agents.
These data also join an increasing body of literature demonstrating the importance of the molecular staging of malignancy. To date, our clinical practice has been largely dictated by the anatomic staging of histologic findings. Lee and colleagues’ data suggest that a patient-specific finding of an altered molecular marker could, a priori, indicate the aggressiveness of an individual thymoma, irrespective of the clinical stage. It is likely within the next decade that the inclusion of molecular staging information into our current pathologic staging paradigms will not only allow us to better define an individual’s prognosis, but also permit us to tailor surgical and nonsurgical interventions to achieve the best clinical outcome.
