Cancer/Testis (CT) Antigens and p53 as Potential Diagnostic Markers in Squamous Cell Carcinomas of the Head and Neck
Kathryn C Piotti, Theresa Scognamiglio, Rita Chiu, Yao-Tseng Chen. Weill Cornell Medical College, New York, NY; Ludwig Institute for Cancer Research, New York, NY
Background: The diagnosis of squamous dysplasia in head and neck (H&N) biopsies is subjective and no markers exist to reliably identify a clonal squamous proliferation. CT antigens comprise a group of proteins that are normally only expressed in germ cells but can be aberrantly activated in cancers, making them potential diagnostic markers. Similarly, p53 gene mutation and protein overexpression is a crucial and clonal event in carcinogenesis. In this study, we evaluated the frequency of CT and p53 expression in H&N squamous cell carcinoma (SqCC) and sought their potential as diagnostic markers in biopsy specimens.
Design: Protein expression of 8 CT antigens (MAGEA, GAGE, SAGE1, NY-ESO-1, CT7, CT10, CT45 and NXF2) and p53 was immunohistochemically evaluated in a tissue microarray of 76 H&N SqCC. 118 biopsy specimens with variable degrees of squamous dysplasia, obtained from 87 cases, were examined on whole sections for 6 CT antigens (MAGEA, GAGE, NY-ESO-1, CT7, CT10, and CT45, in an antibody cocktail) and p53. Unequivocal CT antigen staining in any tumor cell and nuclear p53 staining in >20% of tumor cells were interpreted as positive.
Results: Fifty of 76 invasive SqCC (66%) expressed at least one CT antigen. Overexpression of p53 was found in 27 of 76 cases (36%). Sixty-two SqCC (82%) expressed CT antigen and/or p53. Among the 118 biopsy specimens, 9 were CT positive, 4 were p53 positive, and none was double positive. Of the papillary lesions, 1 (with moderate dysplasia) of 55 was focally CT positive and none were p53 positive. In contrast, of the 65 flat lesions, 8 were CT positive and 4 were p53 positive. These 12 specimens ranged from mild dysplasia to carcinoma in situ histologically and were from 10 patients, 6 of which had a prior or concurrent diagnosis of SqCC. (Figure: moderate dysplasia in a patient with prior SqCC, positive for CT expression).
Conclusions: More than 80% of invasive H&N SqCC showed CT antigen expression and/or p53 overexpression. Although lack of CT/p53 expression is not diagnostically useful, positive CT or p53 immunostains may serve as a specific marker for malignant transformation, distinguishing these lesions from squamous lesions with benign atypia.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 174, Wednesday Morning