Endoglin: A marker of neoplasias or rather of neo-angiogenesis?

To the Editor: We read the recent article by Eleno et al entitled ‘‘Endoglin as a marker of cervical paragangliomas.’’ The authors analyzed and compared the expression of endoglin, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF), and of vascular cell adhesion molecule 1 (VCAM-1) in 5 surgically resected paragangliomas and in specimens of non-neoplastic lung, obtained from 5 patients submitted to pulmonary resection of lung tumors. They found a higher amount of endoglin, HIF-1, and VCAM1, but not of VEGF, in paragangliomas in comparison to lung parenchyma. Finally, they stated that endoglin may have a remarkable diagnostic, prognostic, and therapeutic relevance in tumor development and malignancy of cervical paragangliomas. In our opinion, it would have been useful to analyze the expression of the above-mentioned factors in lung parenchyma also through immunohistochemistry. Indeed, Western Blot does not allow one to assess the precise location of proteins in the different cell types within a tissue. Moreover, histologic examination of lung parenchyma used for the experiments should have been performed, since non-neoplastic alterations may also modify endoglin expression, as this protein may also be expressed by the vessels of regenerating or inflamed tissues. Besides, the authors themselves think that quantification of protein bands exhibited in immunoblots is limited and can hide some interesting considerations. In addition, we do have some reservation about the potential diagnostic and prognostic usefulness of endoglin in paragangliomas as emerging from this study. Endoglin is a 180KDa protein, which is predominantly expressed on cycling endothelial cells in tissues which undergo active angiogenesis. Its expression has been shown in the vessels of several tumors, such as meningiomas or colorectal carcinomas, and endoglin has been demonstrated as a specific marker for neo-angiogenesis in neoplasias. As such, its immunohistochemical evaluation has been largely used in order to assess the microvessels density (MVD) of tumors, which has been demonstrated to be a prognostic marker related to adverse clinical course in terms of overall and disease-free survival. The existence of neo-angiogenic switch in paragangliomas had been previously hypothesized by other authors; nonetheless, in the assessment of MVD they used CD31, a pan-endothelial marker less specific than endoglin for the evaluation of neo-angiogenesis. Thus, we suggest that endoglin immunoexpression may be used to evaluate MVD in cervical paragangliomas so as to analyze whether tumors characterized by higher counts of vessels stained by anti-endoglin antibody display different biological behavior in terms of recurrences and to investigate its correlations with the expression of proangiogenic factors. Head & Neck 32: 970–971, 2010 Published online 2 June 2010 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hed.21501