p53 Protein Expression and p53 Gene Mutation in Thymic Epithelial Tumors:An Immunohistochemical and DNA Sequencing Study

Abstract

p53 protein expression in 34 thymic epithelial tumors was examined immunohistochemically, and p53 gene mutation was detected in selected cases by DNA sequencing, using formalin-fixed and paraffin-embedded tissues. The tumors comprised 12 noninvasive thymomas, 9 invasive/metastatic thymomas, and 13 thymic carcinomas. All the tumors were immunoreactive for p53 protein. The p53-positive tumor cells in noninvasive thymoma were less than 10% (low expressor) in 7 cases and 10% to 50% (moderate expressor) in 5 cases. In invasive/metastatic thymoma, two were low expressors and seven were moderate expressors. In thymic carcinomas, there were nine moderate expressors and four high expressors (with > 50% positive cells). There was significant difference in p53 protein immunopositivity between thymic carcinoma and each of the noninvasive or invasive/metastatic thymomas. The DNA sequencing study confirmed the presence of p53 gene point mutation in all 10 cases examined, including three low expressors. These results suggest that p53 gene mutation is an early event in thymic tumorigenesis, and the p53 protein-positive cells increase with the progression of the tumor. Immunostaining reactivity of p53 may be a useful adjunct to differentiate thymic carcinoma from thymoma.

Expression of podoplanin in thymoma: its correlation with tumor invasion, nodal metastasis, and poor clinical outcome

“…Many studies concerning the expression of p53 protein, bcl-2, and matrix metalloproteinases, counts of argyrophilic nucleolar organizer regions and proliferating cell nuclear antigen, and the Ki-67 index [22][23][24][25][26][27][28] have been conducted to predict the biological behavior of thymomas. In the present study, because we found D2-40 immunoreactivity in metastatic tumor cells within the lymph nodes, we hypothesized that podoplanin expression could be a useful marker of more aggressive behavior of thymomas.…”

Proliferative Activity and Apoptosis in Thymic Epithelial Neoplasms

“…Tateyama et al (35) reported that all thymic epithelial tumors, including noninvasive thymomas, demonstrated overexpression of p53 protein. Here, overexpression of p53 protein was observed only in Type B3 and C thymomas, suggesting that overexpression of p53 protein may be useful as a marker for these more aggressive subtypes.…”

Thymic carcinoma: state of the art review

“…Consequently, CD70 positivity may serve as a marker for thymic carcinoma, and has potential for differentiation of thymic carcinoma from other mediastinal neoplasms, rather than affirmation of a causative pathogenetic relationship between this disease and EBV (26). Other surface antigenic molecules have shown aber- Thymic carcinoma has been associated with increased expression of epithelial membrane antigen, cytokeratin subtypes, and p53 protein (32)(33)(34)(35)(36)(37). The p53 protein is positive in about three quarters (14 of 19) of thymic carcinoma patients (37).…”