Correspondence

Kaposi's Sarcoma after Renal Transplantation

N Engl J Med 2005; 353:846-847August 25, 2005

Article

To the Editor:

The regression of Kaposi's sarcoma in renal-graft recipients after switching from treatment with cyclosporine and mycophenolate mofetil to sirolimus, as reported by Stallone et al. (March 31 issue),1 is remarkable and confirms earlier observations.2,3 However, the immunohistochemical results in this study1 seem to be less convincing. The detection of Flk-1/KDR was reportedly performed on “acetone-fixed kidney sections,” but it is clearly stated that patients had no visceral involvement. Figure 2A, Figure 2B, and Figure 2C of the article do not seem to show greatly different vascular endothelial growth factor (VEGF) expression, certainly not in the range of 5 to 60, as claimed in Figure 2D. The same reservation applies to Figure 3A through 3D with respect to Flk-1/KDR. The visual quantification of immunohistochemical staining on tissue sections in arbitrary units is not reliable, if at all feasible, since it depends largely on technical parameters that cannot be sufficiently standardized and, more important, on the number of cells expressing the antigen studied. For this reason, comparing normal skin with Kaposi's sarcoma tissue seems irrelevant.

Jean Kanitakis, M.D.
Edouard Herriot Hospital, 69003 Lyon, France
kanitakis@lyon.inserm.fr

3 References

1. 1

   Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005;352:1317-1323
   Full Text | Web of Science | Medline

2. 2

   Campistol J, Gutierrez-Dalmau A, Torregrosa JV. Conversion to sirolimus: a successful treatment for posttransplantation Kaposi's sarcoma. Transplantation 2004;77:760-762
   CrossRef | Web of Science | Medline

3. 3

   Lebbe C, Euvrard S, Antoine C, et al. Intérêt du sirolimus dans le traitement de la maladie de Kaposi: 3 observations chez le transplanté rénal. Ann Dermatol Venereol 2004;131:Suppl 1:127-127 abstract.
   CrossRef

To the Editor:

A striking feature in the report by Stallone et al. is that all the patients had Kaposi's sarcoma confined to the skin. This is in contrast to earlier series in which between 44 and 62 percent of patients had more extensive disease, principally involving the lungs or abdominal viscera, at the time of diagnosis.1-4 In those reports, the mean time from transplantation to the diagnosis of Kaposi's sarcoma ranged from 18 to 39 months. For Stallone et al., the median time to diagnosis is 12 months after transplantation. One interpretation of these differences is that greater vigilance by Stallone and colleagues led to a faster diagnosis of Kaposi's sarcoma, allowing the calcineurin inhibitor to be discontinued at an earlier stage of the disease and thus ensuring a better outcome.

Matthew M. Edey, M.B., B.S.
Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom
mattedey@doctors.org.uk

4 References

1. 1

   Montagnino G, Bencini PL, Tarantino A, Caputo R, Ponticelli C. Clinical features and course of Kaposi's sarcoma in kidney transplant patients: report 13 cases. Am J Nephrol 1994;14:121-126
   CrossRef | Web of Science | Medline

2. 2

   Duman S, Toz H, Asci G, et al. Successful treatment of post-transplant Kaposi's sarcoma by reduction of immunosuppression. Nephrol Dial Transplant 2002;17:892-896
   CrossRef | Web of Science | Medline

3. 3

   Moray G, Basaran O, Yagmurdur MC, Emiroglu R, Bilgin N, Haberal M. Immunosuppressive therapy and Kaposi's sarcoma after kidney transplantation. Transplant Proc 2004;36:168-170
   CrossRef | Web of Science | Medline

4. 4

   Zavos G, Bokos J, Papaconstantinou I, et al. Clinicopathological aspects of 18 Kaposi's sarcoma among 1055 Greek renal transplant recipients. Artif Organs 2004;28:595-599
   CrossRef | Web of Science | Medline

To the Editor:

Stallone and colleagues report the regression of dermal Kaposi's sarcoma in kidney-transplant recipients with a change from cyclosporine to sirolimus therapy. This study confirms our experience in two patients.1

We have now observed seven kidney-transplant recipients (at six Spanish centers) in whom dermal Kaposi's sarcoma regressed after a change to sirolimus therapy (Table 1Table 1Characteristics of the Patients.). In the study by Stallone et al., cyclosporine and mycophenolate mofetil were stopped and sirolimus was introduced simultaneously. It could be argued that remission was partially due to the minimization of immunosuppressive therapy. However, in six of the seven cases in our series, the immunosuppressive treatment was reduced considerably before sirolimus therapy was started, but the Kaposi's sarcoma lesions showed no clinical response. Regression could be achieved only after the introduction of sirolimus. This result reinforces the idea that the effect of sirolimus was an antitumor effect, rather than a reduction of immunosuppression.

Alex Gutiérrez-Dalmau, M.D.
Josep M. Campistol, M.D.
Hospital Clínic, 08036 Barcelona, Spain
adalmau@clinic.ub.es

1 References

1. 1

   Campistol JM, Gutierrez-Dalmau A, Torregrosa JV. Conversion to sirolimus: a successful treatment for posttransplantation Kaposi's sarcoma. Transplantation 2004;77:760-762
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Kanitakis raises some technical problems in the evaluation of Flk-1/KDR expression in renal biopsy specimens. We would like to emphasize the presence, in Figure 2A of our article, of autofluorescence of the basement membrane, which was subtracted during quantification. In addition, semiquantitative analysis was confirmed by a computer-based image-analysis system (ImageJ, version 1.33u, National Institutes of Health).1 We agree with Dr. Kanitakis that Flk-1/KDR expression is significantly influenced by the number of cells; indeed, most of the sarcoma cells are Flk-1/KDR-positive, and this is exactly the point raised by Figure 3 in our article.

In response to Dr. Edey: at our center, Kaposi's sarcoma constitutes almost 50 percent of all post-transplantation neoplasms, and for this reason, we have an aggressive screening protocol, including serologic evaluation for human herpesvirus 8 before or after transplantation, or at both times (10 to 15 patients test positive for the virus each year), and a careful skin examination at each visit. This approach allows prompt diagnosis and increases the chance of success with discontinuation of calcineurin, as suggested by Dr. Edey.

Giovanni Stallone, M.D.
Antonio Schena, M.D.
Giuseppe Grandaliano, M.D.
University of Bari, 70124 Bari, Italy
g.grandaliano@nephro.uniba.it

1 References

1. 1

   National Institutes of Health. ImageJ. (Accessed August 4, 2005, at http://rsb.info.nih.gov/ij/.)
   

Citing Articles (3)

Citing Articles

1. 1

   Anthony P. Monaco. (2009) The Role of mTOR Inhibitors in the Management of Posttransplant Malignancy. Transplantation 87:2, 157-163
   CrossRef

2. 2

   Alex Gutierrez-Dalmau, Josep M Campistol. (2007) Immunosuppressive Therapy and Malignancy in Organ Transplant Recipients. Drugs 67:8, 1167-1198
   CrossRef

3. 3

   Bernard Desc??udres, Olivier Giannini, Tanja Graf, J??rg Steiger, Michael Mayr. (2006) No Effect of Sirolimus for Kaposi Sarcoma in a Renal Transplant Recipient. Transplantation 81:10, 1472-1474
   CrossRef