Overexpression of Clusterin in Human Breast Carcinoma

Abstract

Clusterin has been implicated in numerous processes including active cell death, immune regulation, cell adhesion and morphological transformation. The purpose of this study was to examine clusterin expression in a large series of breast carcinomas by immunohistochemistry and in situ hybridization. The study included 40 samples of non-neoplastic glandular epithelia, 42 benign lesions, 15 atypical intraductal hyperplasias, 35 carcinomas in situ, 114 invasive carcinomas, and lymph node metastases from 40 patients. Epithelial normal cells were always negative for clusterin expression and only 19% of the benign lesions presented positive staining. In contrast to the benign lesions, however, the frequency of clusterin positive samples increased in atypical hyperplasias (47%, P ‫؍‬ 0.08), intraductal carcinomas (49%, P ‫؍‬ 0.01) and invasive carcinomas (53%, P < 0.001). Positive staining presented a cytoplasmic pattern, except in 3 cases of invasive carcinomas which had nuclear staining. Clusterin mRNA by in situ hybridization confirmed the specific cellular pattern of clusterin expression by immunohistochemistry. Clusterin expression was associated with large tumor size (P ‫؍‬ 0.04), estrogen and progesterone receptor negative status (P ‫؍‬ 0.02 and P ‫؍‬ 0.001, respectively) and with the progression from primary carcinoma to metastatic carcinoma in lymph nodes (80% metastatic nodes had positive expression) (P ‫؍‬ 0.004). Ten of 15 (67%) primary carcinomas without clusterin expression became positive in lymph node metastases, while most (

Clusterin plays an important role in hepatocellular carcinoma metastasis

“…For instance, introduction of the clusterin gene into renal carcinoma cells resulted in enhanced formation of metastatic nodules in vivo (Miyake et al, 2002). In addition, the expression level of clusterin was contrastive in breast cancer, where normal breast epithelial cells were always negative for CLU expression (Redondo et al, 2000). A similar expression pattern was observed in our recent study on ovarian carcinoma (Xie et al, 2005).…”

“…Although the precise function of CLU remains debatable, a growing body of evidence suggests that overexpression of this protein is implicated in tumorigenesis and metastasis (Steinberg et al, 1997;Redondo et al, 2000;Miyake et al, 2002;Chen et al, 2003;Xie et al, 2005). In a recent study, using a mouse model with Pten conditional prostate deletion, Wang et al (2003) reported that increased CLU expression was found in mutant mouse prostate.…”

“…Interestingly, a growing body of evidence suggested a prominent role of CLU upregulation in tumor pathogenesis and progression. Upregulated expression of CLU has been reported in cancers of the breast (Redondo et al, 2000), ovary (Xie et al, 2005), colon (Chen et al, 2003), prostate (Steinberg et al, 1997), and kidney (Miyake et al, 2002). Several studies have correlated overexpression of CLU with tumor metastasis.…”

Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer

“…39 In prostate cancer, sCLU expression was associated with the development of androgen resistance and it (sCLU) is thought to act as a protective agent against treatment-induced cell death. 8,38 In fact, not many studies showed a decrease in sCLU in tumours like that of a proapoptotic. A few reports do, however, suggest decreased sCLU levels in specific cancers, including nonmelanoma skin cancer, 40 oesophageal squamous cell carcinoma, 41 neuroblastoma, 22 prostate, 11,37 and pancreatic cancer 42 (Table 1).…”

“…For example, sCLU was reported to be a prognostic indicator in tumorigenesis and progression of human breast carcinoma. 38 Furthermore, sCLU has been proposed to be a potentially new prognostic and predictive marker for colon carcinoma aggressiveness, since overexpression of sCLU is reported or observed in highly aggressive tumours as well as metastatic nodules. 3 In addition, in prostate LNCaP cells, CLU appeared to be associated with tumour progression and resistant to chemotherapy treatments in vivo.…”