Emerging prognostic markers related to mesenchymal characteristics of poorly differentiated breast cancers

Abstract

Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K-RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, β-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear β-catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 ± 0.77) with respect to MLG1 (1.26 ± 0.55) and BL (0.86 ± 0.52). SHH expression appeared low in BL (1.00 ± 0.41) and homogenously widespread in MLG1 (1.23 ± 0.63) and MLG3 (1.56 ± 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 ± 0.69 vs 0.82 ± 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 ± 0.78) with respect to BL (0.58 ± 0.55) and MLG1 (1.53 ± 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon.

Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

“…Expression levels of FN , SPARC , LGALS1 , PTX3 , and FSTL were markedly upregulated in our microarray analysis. There are a few reports regarding the relationship between EMT and PTX3/FSTL [35], [36], but it has not yet been elucidated how these affect EMT. SPARC is a matricellular protein known to be a marker of poor prognosis in different cancer types; it is involved in EMT, immune surveillance, and angiogenesis [37].…”

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

“…Moreover, this is in accordance with the highly aggressive nature of poorly differentiated tumors that are prone to nodal/distant metastasis and disease relapse. [35][36][37][38][39] In the in vitro study, CD147 expression is not differential between the cell lines of varied differentiation type and also does not correlate to the migratory/invasive properties. Although other studies have shown that CD147 + cells in ovarian cancer are highly migratory/invasive, 40 this study indicates that it is the percentage of doublepositive (CD147/CD44) cells that correlate with the cellular properties of invasion and migration.…”

Pentraxin-3 is a PI3K signaling target that promotes stem cell–like traits in basal-like breast cancers

“…In breast cancer, Scimeca et al (50) also correlated increased immunohistochemical PTX3 staining with poorly differentiated aggressive breast cancers and related stromal PTX3 production to increased chemotherapy resistance of BCCs (51). Although these collective findings are in support of the promalignant roles we describe for PTX3 in the present work, these observations are in sharp contrast to other studies in which PTX3 was found to exert suppressive roles in tumor pathogenesis.…”