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In Reply:

Department of Experimental Medicine and Pathology, and Division of Plastic Surgery, Institute of Dermatology, University of Rome "La Sapienza", Rome, Italy

We are very grateful to Dr Cao and colleagues for their interest in our paper. One year after the publication of our original article, we have the opportunity to add further data about the correlation of survivin expression in melanoma sentinel lymph nodes and patients' clinical outcome. In the time between writing our paper and today (17 months), none of the 10 patients in the group of survivin-negative sentinel lymph nodes has shown progression of the disease (up to date follow-up periods: 78, 66, 64, 63, 63, 61, 59, 105, 105, and 87 months, respectively; median follow-up of 75.1 months). Thus, we can assure Cao et al that all the 10 patients with survivin-negative results, also with a longer follow-up (previous median follow-up of 52.9 months), are still distributed in the group of patients without progression of disease. On the contrary, in some patients in the group of survivin-positive patients, we observed neoplastic disease progression during the last 17 months. These further data strengthen what we previously "suggested" in our paper, that survivin-based reverse transcriptase polymerase chain reaction (RT-PCR) assay in sentinel lymph nodes of melanoma patients may identify a group of patients at risk of disease progression. This was merely suggested, since we were aware that the number of patients enrolled on the study is too exiguous to make an extrapolation of results and evaluate the real role of survivin expression as a prognostic marker.

In reply to the other considerations about our paper taken into account by Cao et al, we would underline the following: (1) based on previous literature data, the aim of our study was the analysis of apoptosis-related gene expression in sentinel lymph nodes, identified positive for occult melanoma cells using RT-PCR, in order to search for a possible prognostic role of some of these genes. Since it has been demonstrated that hematoxylin and eosin staining underestimates the true incidence of melanoma metastases, we selected sentinel lymph nodes by means of RT-PCR and not by histologic technique. Thus, to select the samples to include in the study, we used tyrosinase and melanoma-inhibitory activity RT-PCR. Therefore, we did not investigate the correlation between tyrosinase and melanoma-inhibitory activity expression and outcome of patients; this was the aim of a series of previously published reports. In addition, since we know that the tyrosinase assay can give false-positive results for the presence of nevus cells, as reported in our paper, all the tyrosinase-positive samples were investigated by an experienced pathologist to exclude samples positive for melanocitic nevus cells from the study; (2) in regards to MART-1, in a recent report, we studied the correlation between tyrosinase and MART-1 expression in sentinel lymph nodes and the outcome of malignant melanoma patients, and found that the RT-PCR negativity is a very favorable prognostic factor¹; (3) and in response to the comments concerning the immunohistochemical data, the results have been set out in great detail in the paragraph, and they strictly correlate with the results in Table 1 of our article.² The positivity of all three proteins correlated to infiltrating cells is related only to positive samples (as is clearly described in the last sentence of the immunohistochemistry paragraph).

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Ribuffo D, Gradilone A, Vonella M, et al: Prognostic significance of reverse transcriptase-polymerase chain reaction-negative sentinel lymph nodes in malignant melanoma. Ann Surg Oncol 10:396-402, 2003[CrossRef][Medline]

2. Gradilone A, Gazzaniga P, Ribuffo D, et al: Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from melanoma patients. J Clin Oncol 21:306-312, 2003[Abstract/Free Full Text]

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