- Paper Report
- Open Access
Clusterin in human breast cancer
- Syed Mohsin1
© Current Science Ltd 2000
- Published: 1 December 2000
- Breast cancer
Clusterin is an 80 KDa protein encoded by a gene located on chromosome 8 (8p21). It is highly conserved across species and shows wide tissue distribution. It is implicated in a variety of activities such as programmed cell death, regulation of complement mediated cell lysis, membrane recycling, cell-cell adhesion and src induced transformation. As a part of the MAC of complement, it acts as a complement inhibitor. Based on this role, it was postulated that tumors overexpressing clusterin may evade destruction by complement system and progress to more aggressive tumors.
To evaluate expression of clusterin in benign, premalignant lesions, invasive and metastatic breast cancer. To study the relation of clusterin to other factors such as hormone receptors, proliferation and apoptosis and clinical outcome.
Breast samples from 40 normal breasts, 42 benign lesions, 20 atypical hyperplasias, 35 in situ carcinomas, 114 invasive, and 40 metastatic breast cancers were studied using immunohistochemistry (IHC; monoclonal antibody E5) and in situ hybridization (ISH). In addition, hormone receptors, proliferation and apoptosis (TUNEL) were also evaluated. Greater than 10% staining was considered positive.
Clusterin signal was mainly seen in the cytoplasm of tumor samples. Normal breast epithelium did not express clusterin. Clusterin was found in 19% of benign, 47% of atypical hyperlasias, 49% in situ, 53% invasive and 80% metastatic tumors. In 67% of cases with clusterin negative primary cancer, metastatic tumors were positive. Of the clusterin positive primary cancers, 88% were also positive at the metastatic site. ISH and IHC results were concordant. Clusterin expression was significantly related to bad prognostic factors such as high histologic grade, larger tumor size, negative hormone receptor and lower apoptosis index. Clusterin was not related to clinical outcome in uni- or multivariate analysis.
Overexpression of clusterin is more common in the late stages of mammary tumor progression. Although inhibition of MAC of complement may be an explanation for these results, lower apoptosis in clusterin positive tumors could also be involved. However, the exact mechanism of clusterin function and its possible role in tumorigenesis remains unclear.