Loss of S100 antigenicity in metastatic melanoma

Dara L. Aisner, Ajay Maker, Steven A. Rosenberg, David M. Berman

Research output: Contribution to journalArticlepeer-review


Melanoma is a highly malignant disease that may initially present as a poorly differentiated metastatic tumor. Therefore, the S100 immunostain, immunoreactive in 96% to 99% of melanoma, is used to evaluate poorly differentiated malignant tumors. To develop criteria for correctly diagnosing S100-negative melanomas, we studied the immunohistochemical profile of 1553 patients enrolled in ongoing National Cancer Institute clinical trials for melanoma. Seventeen patients (1%) had metastatic melanoma specimens that were negative for S100. Of the 17 S100-negative lesions, 10 (59%) were immunoreactive for both GP100 and MART-1. Of the 17 S100-negative cases, 13 had a documented primary melanoma. Twenty-four percent of the S100-negative cases had an ocular primary, whereas only 6% of all melanomas had an ocular origin. In 11 of the 17 cases with previous surgical specimens, a prior documented S100-immunoreactive specimen was identified in 9 cases (82%). The time interval for loss of S100 immunoreactivity ranged from 3 weeks to 3 years (average, 13.5 months). There was no association between S100-negative status and histological appearance or site of metastasis. We conclude that all S100-negative melanomas could be correctly identified by negative workup for carcinoma, lymphoma, and sarcoma plus (1) GP100/MART-1 immunoreactivity and/or (2) prior documentation of melanoma.

Original languageEnglish (US)
Pages (from-to)1016-1019
Number of pages4
JournalHuman pathology
Issue number9
StatePublished - Sep 2005


  • Antigenicity
  • Diagnosis
  • Melanoma
  • S100

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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