Caveolin-1 expression in human breast lobular cancer progression

Abstract

Caveolin-1 is the principal structural protein of caveolae, and caveolin-1 gene plays a role as a tumour suppressor gene in human mammary cancer-derived cells. However, limited data are available concerning caveolin-1 expression in human breast cancer tissue. We evaluated caveolin-1 expression in normal lobular epithelial cells and in the whole human lobular neoplasia spectrum disease, with the aim to examine differences of caveolin-1 expression in human lobular neoplasia progression. We selected 147 cases of pure lobular lesions, ie lobular intraepithelial neoplasia and invasive lobular carcinoma, from 112 patients. Presence of caveolin-1 was evaluated by immunohistochemistry. Among 81 lobular intraepithelial neoplasia lesions studied, 43% were associated with invasive lobular carcinoma, with positive correlation between lobular intraepithelial neoplasia grade and presence of invasive component (P ¼ 0.01). In total, 64% of lobular lesions were positive for caveolin-1 (81% lobular intraepithelial neoplasia and 42% invasive lobular carcinoma), and a significant difference in terms of caveolin-1 expression was present between lobular intraepithelial neoplasia and invasive lobular carcinoma (P ¼ 0.0001). Variations in caveolin-1 expression were evident among the different lobular intraepithelial neoplasia grades (91% grade 1, 68% grade 2, 35% grade 3); the difference was significant comparing lobular intraepithelial neoplasia grade 3 vs 1 (P ¼ 0.0001) and grade 3 vs 2 (P ¼ 0.007) but not grade 1 vs 2. Furthermore, significant differences were found between lobular intraepithelial neoplasia grades 1 and 2 vs invasive lobular carcinoma (P ¼ 0.0001), but not between lobular intraepithelial neoplasia grade 3 and invasive lobular carcinoma (P ¼ 0.196). In conclusion, variations of caveolin-1 expression may have an important role in the progression of human breast lobular cancer; in addition, they confirm the powerful clinical impact of the lobular intraepithelial neoplasia classification for lobular intraepithelial neoplasia, supporting the direct origin of invasive lobular carcinoma from clonal expansion of the lobular intraepithelial neoplasia lesions cells.

Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance

“…To this end, Joshi et al [60] have recently shown phosphorylated caveolin-1 to co-operate with Rho/ROCK and FAK-dependent signalling pathways promoting tumour cell invasion and metastasis in breast cancer. Such studies are consistent with clinical data showing a positive correlation between caveolin-1 expression (although distinction between phosphorylated and nonphosphorylated forms not addressed) and poor patient survival in highly aggressive invasive breast cancers [42][43][44]61]. The induction of caveolin-1 and the presence of a pool of phosphorylated caveolin-1 in gefitinib treated TAM-R cells may have profound implications for the overall function of caveolin-1 in these cells and for the clinical management of tamoxifen-resistant breast cancers involving the use of EGF-R inhibitors [62].…”

“…These include amongst others the activation of the EGFR/RAS/ERK signalling pathway, increased cell proliferation and cell migration, initiation of mammary gland dysplasia, enhanced anchorage independent growth and metastatic potential. Conversely, several clinico-pathological studies correlate caveolin-1 over-expression with aggressive features of certain breast cancers, most notably the basal-like and inflammatory invasive subtypes [42][43][44]. However, none of these studies have explored the functional role of caveolin-1 in the development of hormone resistant breast cancer.…”

Overexpression of Caveolin-1 in Cancer-Associated Fibroblasts Predicts Good Outcome in Breast Cancer

“…histological type of breast cancer, with ILC showing significantly lower expression than IDC and mixed carcinoma, and the differences were statistically significant (p = 0.000). Although Perrone [16] reported that 42% of ILC expressed Cav-1, we found that Cav-1 was not expressed in 19 cases of ILC. Stromal Cav-1 was negative in 10 patients, with the other 9 cases being 1+.…”

Caveolin-1 overexpression correlates with tumour progression markers in pancreatic ductal adenocarcinoma

“…The expression level of Cav-1 depends on the type of neoplastic cell investigated (Williams and Lisanti 2005). While Cav-1 has been shown to be down-regulated in ovarian (Park et al 2005;Wiechen 2001a), lung (Belanger et al 2004), and mesenchymal sarcomas (Wiechen 2001b), Cav-1 was overexpressed in bladder (Fong et al 2003), esophageal , prostate (Yang et al 2007) and breast carcinomas (Liedtke et al 2007;Perrone et al 2009). The most conflicting results were observed in gastrointestinal cancers: the expression of Cav-1 was reduced in human colon carcinoma cell lines (Bender et al 2000), while an increased level of Cav-1 was reported in esophageal and colonic tumors Kim et al 2006).…”