Target Marker for Immunotherapy in Metastatic Melanomas of Rare Morphology Subtypes.
Yen-Chun Liu, Steven A Rosenberg, Chyi-Chia Richard Lee. NCI, NIH, Bethesda, MD
Background: Metastatic melanoma can be a challenging diagnosis with its diversified morphology. Metastatic melanomas with rhabdoid or desmoplastic features are rare but should be included in the differential diagnoses when evaluating tumors with rhabdoid morphology or desmoplasia. Immunohistochemical staining profiling of such tumor is not only important for correct diagnosis but also critical for potential application of the adoptive cell transfer immunotherapy. By using gene-modified lymphocytes targeting a specific tumor marker, adoptive cell transfer has been shown to be a highly effective treatment for metastatic malignant melanoma. In this study, with 6 different antibodies, we characterize the expression of potential immunotherapy target markers for melanomas of rare morphology subtypes.
Design: We analyzed the expression of Melan A/MART-1, HMB45, tyrosinase, S100, KBA.62 and NY-ESO-1 by immunohistochemistry on 8 metastatic melanoma with rhabdoid features and 5 metastatic melanomas with desmoplastic changes collected between April 2008 and April 2009. Five primary melanoma lesions corresponding to the metastatic rhabdoid lesions are available for review and are concurrently examined.
Results: In our series, conventional melanoma markers including Melan A/MART-1, HMB45, Tyrosinase have high sensitivities in detecting metastatic melanomas with rhabdoid features (S100:100%, Melan A/MART-1:100%, HMB45:75%, Tyrosinase:88.9%) but low sensitivity in detecting melanomas with desmoplastic features (S100:100%, MART-1:20%, HMB45:20%, Tyrosinase:40%). The relatively new melanoma marker KBA.62 stains positive in all the rhabdoid and desmoplastic lesions (sensitivity:100%). NY-ESO-1, a cancer-testis antigen and an ideal marker for adoptive cell transfer immunotherapy, is expressed in 37.5% of the metastatic melanoma lesions with rhabdoid features (n=8) and 50% of the desmoplastic lesions examined (n=4). Intriguingly, none of the 5 primary lesions for the metastatic rhabdoid specimens have recognizable rhabdoid morphology.
Conclusions: Our results indicate that melanomas with rhabdoid features can be accurately diagnosed with conventional and novel melanoma markers though desmoplastic lesions are usually only positive for S100 and KBA.62. NY-ESO-1 is expressed in 37.5-50% of the lesions examined, which provides histologic evidence for using this specific adoptive cell transfer therapy with relatively small side effect in these patients. The metastatic rhabdoid melanomas do not have rhabdoid morphology in their primary lesions in our series.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 107, Tuesday Morning