Deregulated expression of the PCPH proto-oncogene in human breast cancers.

We performed a study on the expression of the PCPH protein in samples corresponding to normal, pre-malignant and malignant stages of the human mammary gland by using protocols of immunohistochemistry and Western blot analysis with anti-PCPH specific antibodies. Results obtained from the immunohistochemical study showed that PCPH was undetectable in samples of normal breast and of benign diseases, with the exception of glands presenting apocrine metaplasia, in which an intense PCPH stain was observed both in the basal cytoplasm of the secretory cells and in the apocrine secretion. On the contrary, an intense labeling was observed in the cytoplasm of neoplastic cells in samples of both ductal and lobular carcinoma in situ, with this immunostaining increasing even further in samples of infiltrating carcinoma, both ductal and lobular. Western blot analyses of the same set of samples detected a 47 kDa form as the main PCPH polypeptide present in all cases studied. However, whereas this 47 kDa polypeptide was the only PCPH form detected in normal and pre-malignant samples, multiple forms could be detected in carcinoma samples, indicating the presence of altered PCPH polypeptides at these disease stages. These results were in agreement with those from the immunohistochemical study and together indicated that PCPH protein expression represents a good molecular marker to follow the process of human breast carcinogenesis. Furthermore, these results suggested that characterization of the pattern and level of PCPH expression may be a useful tool for early identification of breast cancers.