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From the Division of Surgical Oncology, University of Louisville, James Graham Brown Cancer Center, Louisville, Kentucky.
Correspondence: Address correspondence to: Kelly M. McMasters, MD, PhD, University of Louisville, James Graham Brown Cancer Center, 529 S. Jackson St., Louisville, KY 40202; Fax: 502-629-3393; E-mail: kelly.mcmasters{at}nortonhealthcare.org
Prognostic factors are a dime a dozen. In melanoma, there are dozens of prognostic factors that have been proposed over the years, many of which have fallen by the wayside. The status of the regional lymph nodes has long been considered the single most important independent prognostic factor for patients with melanoma.1 Breslow thickness has become well established as the most important feature of the primary tumor. Clark’s level has largely been superseded by Breslow thickness but still has prognostic significance, especially for thin melanomas. Ulceration of the primary tumor has become a very important prognostic factor that has been underrecognized in the past. Ulceration will be featured prominently in the new American Joint Committee on Cancer (AJCC) staging system for melanoma that will take effect in 2002.2,3
The new AJCC staging system incorporates tumor thickness, ulceration, and nodal status. Clark’s level also is used for subclassification of T1 tumors. It does not incorporate the innumerable other prognostic factors that have been proposed over the years. Having taken part in the AJCC Staging Committee meetings for melanoma, I can attest to the fact that it is not easy to get melanoma experts to agree on a staging system comprised of even these few factors. Stage groupings were constructed based on incremental differences in survival. It was felt that these stage groupings could help to stratify patients for clinical trials and to provide homogeneous prognosis-based patient populations for study.
In this issue of Annals of Surgical Oncology, Chung and colleagues4 from the John Wayne Cancer Institute report the use of the serum TA90 immune complex assay to predict recurrence and survival among patients with thick primary melanomas. The TA90 assay, developed at the John Wayne Cancer Institute, was discovered as an antigen found in the urine and sera of patients with metastatic melanoma. Previously, Dr. Morton’s group has reported a significant correlation between TA90 status and outcome.5,6 In the present study, patients with thick primary tumors (>4 mm thick) were evaluated. The actuarial 5-year survival rate for patients with a negative TA90 test was 89% versus 44% with a positive TA90 test. Furthermore, using a combination of TA90 and sentinel lymph node biopsy, it was possible to identify patients with thick primary tumors who have an estimated 5-year survival rate ranging from 18% for those who were sentinel node–positive and TA90-positive versus 82% for those who were sentinel node–negative and TA90-negative. Interestingly, the patients who were sentinel node–positive and TA90-negative had an estimated 5-year survival rate of 92%, which may simply be a reflection of the small numbers of patients in the study.
The differences in the survival curves for TA90-negative and -positive patients are, quite simply, huge. TA90 does not appear to be like other prognostic factors where small changes in the estimated survival rate are predicted that barely reach significance on multivariate analysis. TA90 seems to hold the keys to life or death in melanoma. Few of us can argue with the impressive differences in recurrence and survival predicted by this test, if in fact these results can be reproduced.
Several questions, of course, remain. What is TA90, what is its function, and why is it found in the serum and urine of patients with melanoma? When will the TA90 gene be cloned so that we can get further information that may help us engineer new molecular or immunologic strategies for treatment of melanoma? Does the quantitative titer of TA90 correlate with outcome? What is the optimal timing for TA90 evaluation? When TA90 is found to be positive, does it remain positive for the remainder of the patient’s follow-up period? How does TA90 correlate with positron emission tomography scan and other imaging studies? Do TA90 positivity and titers decline during and after adjuvant therapy with interferon, cancer vaccines, or other therapies? For which patients should this test be used? When will this assay be available outside of the John Wayne Cancer Institute for study?
The answers to these and other questions will undoubtedly be forthcoming in the next few years. The available evidence from the ongoing studies at the John Wayne Cancer Institute, however, suggest that TA90 is not just another prognostic factor to add to a multitude of others in our multivariate analyses. Understanding TA90 may fundamentally change our understanding of melanoma metastasis. If this assay can be validated in prospective studies, it certainly will take its rightful place in the AJCC staging system. And, if it is as good as it looks so far, we may have fewer prognostic factors to haggle about in those staging committee meetings.
Received for publication October 9, 2001. Accepted for publication October 10, 2001.
REFERENCES
This article has been cited by other articles:
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  J. K. Wall, M. Florero, N. A. Accortt, R. Allen, M. Kashani-Sabet, E. Morita, and S. P. L. Leong Impact of Multiple Lymphatic Channel Drainage to a Single Nodal Basin on Outcomes in Melanoma Arch Surg, August 1, 2007; 142(8): 753 - 758. [Abstract] [Full Text] [PDF]
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