Cancer/Testis (CT) Antigens and p53 Are Preferentially Expressed in High-Grade and Metastatic Mucoepidermoid Carcinoma.
Kathryn C Piotti, Theresa Scognamiglio, Rita Chiu, Lloyd J Old, Yao-Tseng Chen. Weill Cornell Medical College, New York; Ludwig Institute for Cancer Research, New York
Background: CT antigens comprise a group of proteins that are normally only expressed in germ cells and yet are aberrantly activated in a wide variety of human cancers, making them attractive candidates for targeted cancer immunotherapy as well as potential diagnostic tumor markers. Higher frequency of CT antigen expression often correlates with tumor progression and with higher tumor grade, and this has been observed in metastatic melanoma, high-grade urothelial carcinoma and hormone receptor-negative breast cancer. The expression of CT antigens in salivary gland tumors, however, has not been studied.
Design: Protein expression of 6 CT antigens (MAGEA, NY-ESO-1, CT7, CT10, CT45 and GAGE) was immunohistochemically evaluated in tissue microarrays containing 137 pleomorphic adenomas, 41 Warthin's tumors, 8 basal cell adenomas, 33 mucoepidermoid carcinomas (MEC), 21 adenoid cystic carcinomas, 3 acinic cell carcinomas, and 2 carcinomas ex pleomorphic adenoma. Three tissue cores from each tumor were evaluated. Unequivocal nuclear staining in any tumor cells was considered positive. p53 overexpression was also evaluated and tumors with at least moderate staining in >20% of tumor cell nuclei were interpreted as positive.
Results: All benign salivary tumors were negative for the six CT antigens and p53 (0/185). In carcinomas, CT antigen was detected in 5/33 (15%) MEC and 2/21 adenoid cystic carcinomas; p53 staining was observed in 5 MEC and 1 carcinoma ex pleomorphic adenoma. Of 33 MEC in the series, 14 were either histologically high-grade or had evidence of metastasis, and 6 (43%) of these were positive for CT antigen (2 cases), p53 (2 cases) or both (2 cases), the latest subgroup including a case of brain metastasis that simultaneously expressed MAGEA, NY-ESO-1, GAGE and p53. In contrast, of the 19 MEC with low or intermediate grade and no evidence of metastasis, only 2 (10%) cases were positive for either p53 (1 case) or CT (1 case, NY-ESO-1 only). This difference is statistically significant (p=0.047).
Conclusions: Benign salivary gland tumors do not express CT antigens or p53. Carcinomas only infrequently express these antigens; however, high-grade and metastatic mucoepidermoid carcinomas showed preferential expression of CT antigens and p53. This finding, although preliminary due to sample size, suggests CT antigens and p53 as potential markers for aggressive clinical behavior in mucoepidermoid carcinoma. Additional studies to confirm this finding are ongoing.
Category: Head & Neck
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 144, Wednesday Morning