Expression of Cancer Testis Antigens (CTAs) and Melanocyte Differentiation Antigens (MDAs) in Malignant Melanoma of the Ano-Rectal Mucosa (MMARM)
Achim A Jungbluth, Denise Frosina, Megan Holz, Martin Weiser, Klaus J Busam. Ludwig Institue for Cancer Research, New York, NY; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: MMARMs are rare tumors carrying a poor prognosis. Recent data indicate that melanomas, not exposed to UV-light differ from their cutaneous counterparts on an antigenic and molecular level. MDAs such as Melan-A, gp100 and tyrosinase are expressed in cells and tumors of melanocytic lineage while CTAs such as MAGE and NY-ESO-1 are tumor-associated antigens which are expressed in various tumor types and in normal adult tissues solely in male germ cells. MDAs are standard diagnostic markers for melanocytic lesions. Due to their expression pattern, CTAs as well as MDAs are regarded potential vaccine targets for the immunotherapy of melanoma. However, little is known about the presence of MDAs and CTAs in MMARM.
Design: Paraffin blocks from 13 cases of MMARM were available. Standard IHC employing antigen retrieval techniques was done using mostly in-house generated(*) as well as commercial mAbs/to the following antigens: MA454*/MAGE-A1, 57B/MAGE-A4, CT7-33*/MAGE-C1, CT10#5*/MAGE-C2, #26/GAGE, E978*/NY-ESO-1; A103*/Melan-A, HMB45/gp100, and T311*/tyrosinase.
Results: MDAs Melan-A, tyrosinase and gp100 were all positive in all tested MMARM. Expression was mostly homogeneous; only one case showed solely focal expression of Melan-A and another case displayed focal presence of gp100.
All 13 MMARM cases showed expression of at least 1 CTA! MAGE-A4, MAGE-C1 and GAGE showed the highest incidence and were both positive in 10/13 (77%) cases, while MAGE-A1 showed the lowest expression (6/13 cases, 46%), NY-ESO-1 and MAGE-C1 were present in 9/13 (69%) and 7/13 (54%) cases respectively. Interestingly, 7/13 (54%) cases showed homogeneous CTA expression in more than 50% of the tumor while the presence in the remaining cases varied from <%5 to 50% of the tumor area.
Conclusions: Little is known about the presence of MDAs and CTAs in MMARM. Here we show that Melan-A, tyrosinase and gp100 show a high incidence and homogeneous expression in MMARM. CTAs show a lower incidence and a less homogeneous expression than MDAs. However, a majority of MMARMs show homogeneous presence of at least 1 CTA.
Our data indicate that unlike on a molecular level, protein expression of CTAs as well as MDAs in MMARM resemble the expression of their cutaneous counterparts. Moreover, due to their homogeneous presence in a majority of cases, MMARM may be susceptible to vaccine-based immunotherapy employing CTAs.
Monday, March 19, 2012 1:00 PM
Poster Session II # 127, Monday Afternoon