Expression of Cancer Testis (CT) Antigens in Merkel Cell Carcinoma (MCC)
AA Jungbluth, D Frosina, K Iversen, G Sapgnoli, KJ Busam. Ludwig Institute for Cancer Research New York, New York, NY; University Hospital, Basel, Switzerland; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: CT antigens such as MAGE, CT7 and NY-ESO-1 have been identified by their ability to elicit B- and T-cell responses in the autologous host. They are expressed in a wide variety of cancers but not in normal adult tissues except testicular germ cells. Based on their immunogenecity and tumor-associated expression pattern, CT antigens are under investigation as vaccine targets for the immunotherapy of cancer. They may also be useful for diagnostic applications in surgical pathology. We previously identified several novel CT antigens and generated monoclonal antibodies (mAbs) for protein expression studies of various CT antigens. MCCs are rare neuroendocrine cutaneous carcinomas. They occur most commonly in older patients, and tend to metastasize early. Except surgical removal of the primary, there is no effective treatment for advanced disease. Hence, MCCs carry a dismal prognosis. Expression of CT antigens has not been analyzed in MCCs albeit their presence may offer additional treatment options and/or could be helpful as diagnostic tool in surgical pathology.
Design: 60 cases of MCC were retrieved from the archives of the Dept. of Pathology of MSKCC. Tissue micro arrays were constructed employing a minimum of 3 representative cores/case. Immunohistochemistry (IHC) was done using the following mAbs (to the following antigens): MA454 (MAGE-A1), M3H67 (MAGE-A3), 57B (MAGE-A4), E978 (NY-ESO-1, CT7-33 (CT7/MAGE-C1), #26 (GAGE, Transduction Labs, Lexington, KY), CT10#5 (CT10/MAGE-C2). Immunoreactivity was graded according to the amount of immunopositive tumor cells as: foc - 5%; + - 5-25%; ++ 25-50%; ++ - 50-75%; ++++ - >75%.
Results: There was little expression of CT antigens. Most prevalent staining was seen with mAb M3H67 to MAGE-A3. Expression for each mAb was as follows: MA454: 0%, M3H67: 6.7%, 57B: 4.6%, CT7-33: 33:2.6%, CT10#5: 2.5%, E978: 2.2%, #26: 2.6%. Most positive cases showed restricted expression of antigens and only two cases were immunopositive in more than 75% of the tumor.
Conclusions: Though other skin cancers such as melanoma are among the tumors with the most prevalent expression, CT antigens are poorly expressed in MCC. Moreover, the few CT antigen positive cases show a very restricted expression pattern within the lesion. We conclude that CT antigens are neither useful diagnostic markers nor useful vaccine targets in Merkel Cell Carcinoma.
Tuesday, March 10, 2009 9:00 AM
Platform Session: Section E, Tuesday Morning