Detection of human polyomavirus proteins, T-antigen and agnoprotein, in human tumor tissue arrays

Abstract

Expression of the human polyomavirus JCV genome in several experimental animals induces a variety of neural origin tumors. The viral proteins, T-antigen and Agnoprotein, contribute to the oncogenesis of JCV by associating with several tumor suppressor proteins and dysregulating signaling pathways, which results in uncontrolled cell proliferation. In addition, T-antigen and Agnoprotein have been associated with DNA damage and interfering with DNA repair mechanisms. In this study, we have utilized commercially available tissue arrays of human tumors of various origins and demonstrated the expression of both T-antigen and Agnoprotein in some, but not all, tumors of neural and non-neural origin. Most notably, more than 40% of human glioblastomas and greater than 30% of colon adenocarcinomas express viral proteins. The detection of viral transforming proteins, T-antigen and Agnoprotein in the absence of viral capsid proteins suggests a role for JCV in the development and/or progression of human tumors. These results invite further large-scale investigation on the role of polyomaviruses, particularly JCV in the pathogenesis of human cancer.

Fig. 1

Detection of T-antigen in human cancer tissue arrays. Immunohistochemistry for the JCV early protein T-antigen performed in different human tissue arrays shows robust expression in the nuclei of neoplastic cells from astrocytic tumors, including low-grade diffuse astrocytomas (Panel A), anaplastic gliomas (Panel B), and GBMs (Panel C). In contrast, no expression of T-antigen was found in any cell type from normal brain cylinders present in the same array (Panel D). T-Antigen expression is robust in neoplastic epithelial cells from colon adenocarcinomas (Panel E), while is undetectable in the normal colon (Panel F). T-Antigen expression was also found in the nuclei of malignant epithelial cells from lung carcinomas (Panel G), breast lobular carcinomas (Panel I), and serous adenocarcinomas from the ovary (Panel J), while stromal cells in the same sections remain negative. Nephroblastomas, primitive tumors of the kidney, also show expression of T-antigen (Panel H). Finally nuclear expression of T-antigen was noted in epithelial cells from serous and follicular carcinomas of the thyroid gland (Panels K and L, respectively). All low power views (upper panels) original magnification 40×. All high power views (lower panels) original magnification 400×. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Fig. 2

Detection of Agnoprotein in human cancer tissue arrays. Immunohistochemical studies performed in tissue arrays of different human tumor phenotypes demonstrates the expression of the viral accessory product, Agnoprotein in the cytoplasm of neoplastic astrocytes in different degrees of glial tumors ranging from low-grade astrocytomas (Panel A), to anaplastic tumors (Panel B) and glioblastoma multiforme (Panel C). In a different array, Agnoprotein is detected in the cytoplasm of neoplastic epithelial cells from colon adenocarcinomas (Panel D), esophageal carcinomas (Panel E), and cases of breast lobular carcinomas (Panel F). All panels original magnification 400×. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]