Abstract Abstract #4044 Background: Recent studies identified a uncharacterized gene that encodes a molecule named as cytokeratin-associated protein in cancer (CAPC). RT-PCR analysis detected significant elevation of CAPC mRNA in 26 of 33 human breast cancers. Our current study attempted to elucidate CAPC protein expression profile in human breast tissues, to assess: [1] if CAPC expression is associated with tumor progression and invasion, and [2] if CAPC is co-expressed with BP1 and c-erbB2, two known invasiveness and aggressiveness-related proteins.
 Materials and Methods: Consecutive sections were prepared from paraffin-embedded breast tissues from 100 female patients with breast tumors that harbored co-existing normal, hyperplastic, in situ, and invasive components. Sets of four adjacent sections from each case were subjected to immunohistochemistry for CAPC, BP1, c-erbB2, and Ki-67. The expression status of these molecules in different tissue components were statistically compared.
 Results: In normal breasts and hyperplastic or in situ breast lesions, CAPC positive cells were generally distributed as duct or acinar clusters with a distinct boundary with their CAPC negative counterparts. Under low magnification of H&E stained sections, these CAPC positive duct or acinar clusters were morphologically indistinguishable from their CAPC negative counterparts. Under high magnification, however, the myoepithelial cell layers of these CAPC positive clusters were focally disrupted, and the associated epithelial cells often showed malignancy-associated nuclear alterations. Both the number of CAPC positive cells and the intensity of CAPC immunostaining linearly increased with tumor progression and invasion. In invasive lesions, a vast majority of cancer cells in over 80% of the cases expressed high levels of CAPC. A majority of the normal, benign, and malignant tumors with high levels of CAPC showed substantially higher expression of BP1 and c-erbB2, along with a higher proliferation index, compared to their morphologically similar CAPC negative counterparts . In non-mitotic cells, CAPC was localized mainly in the cytoplasm. In malignant mitotic cells, high levels of CAPC expression were localized close to the cell membrane, forming a ring-like structure surrounding condensed chromosomes. In contrast, no distinct CAPC was detected in normal or hyperplastic mitotic cells.
 Discussion: These findings suggest CAPC might be a tumor specific marker that could be used for the development of diagnostic and/or therapeutic agents.
 Acknowledgment: Supported in part by grant BCTR0706983 from The Susan G. Komen Breast Cancer Foundation and grant 2006CB910505 from the Ministry of Chinese Science and Technology Department. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4044.