Pathobiology of pp32 in Breast Cancer

Abstract : Breast cancers differ from benign breast epithelium through prominent expression of oncogenic pp32 gene family members. Whereas benign breast epithelium predominantly expresses pp32, a tumor suppressor, breast cancers express pp32rl and pp32r2, which are oncogenic. The study purpose is to confirm and extend these preliminary results, to develop practical means to assay pp32 gene family members in clinical samples, and to determine the clinical significance of their presence in pre-invasive breast disease. The approved proposal encompassed four broad tasks: (1) characterization of the pp32 expression phenotype of a larger sample of 40 breast cancers; (2) development of a practical assay for altered pp32 transcripts in archival tissue; (3)determination of the association of specific pp32 variants in laser capture microdissected DCIS with invasion and with high-grade comedo DCIS; and 4 application of the results in a retrospective study (if 3 shows meaningful correlations) to a population of patients with follow-up. During the reporting period, we recognized that microheterogeneity of pp32 gene family expression in tissue would best be assessed by an in situ hybridization method that would have better resolution than laser capture. This technically formidable task is now nearly complete and will facilitate rapid completion of the remaining aims.