**4.3 140Cap in human breast cancer**

So far, few data are available on p140Cap in human tumors. Immunohistochemistry analysis of normal mammary tissue show that p140Cap expression is confined to the luminal cells of alveoli, suggesting that in normal conditions p140Cap might play a role in mammary cell differentiation. In contrast, in human breast tumours p140Cap is not expressed in 70% of tumour specimens, showing an inverse correlation with the state of malignancy.

Fig. 7. p140Cap expression is lost in aggressive human breast cancers. In the histogram we reported the number of tumours positive (white) or negative (grey) for p140Cap expression according to tumour grade (low grade G1/G2, high grade G3), number of mitosis 10/10 HPS (M1 Mitosis < 10, M2 Mitosis>10), Ki67 proliferation index (Ki67+>24% , Ki67- <24%), Estrogen Receptor staining (ER-, ER+), Progesterone Receptor staining (PR-, PR+), infiltration in lymph nodes (Node+, Node-), EGFR staining (EGFR+), E-Cadherin staining (E-Cad-). The figure is modified from Damiano *et al*., 2010.

Interestingly, 94.8% of aggressive G3 tumours, 87% of the Node +, 86.5% of tumours with a mitosis major number of 10/10HPF, and 76% of highly proliferative tumours (revealed by Ki67 staining), lose p140Cap expression. Moreover, none of the E-cadherin negative and EGFR positive tumours express p140Cap, suggesting mutually exclusive correlation between EGFR and p140Cap expression (Figure 7) (Damiano *et al*., 2010). Therefore, although limited, these data point out that only low grade breast tumors express p140Cap. Further analysis is required to draw a general picture of the relevance of p140Cap in human breast cancers, and to delineate a potential use of p140Cap as a diagnostic and prognostic factor.

In conclusion, p140Cap is involved in direct interactions with several proteins (Figure 1). The p140Cap binding partners are mainly implicated in membrane fusion and actin cytoskeleton remodelling. p140Cap association to p130Cas, Src, Cortactin and the presence of a putative actin binding domain in the p140Cap sequence, suggest that p140Cap could be an actin binding protein. Indeed, p140Cap has been described to co-localize with actin stress fibers and cortical actin both in epithelial and in neuroectodermal cells (Chin *et al.*, 2000; Di

So far, few data are available on p140Cap in human tumors. Immunohistochemistry analysis of normal mammary tissue show that p140Cap expression is confined to the luminal cells of alveoli, suggesting that in normal conditions p140Cap might play a role in mammary cell differentiation. In contrast, in human breast tumours p140Cap is not expressed in 70% of tumour specimens, showing an inverse correlation with the state of

Fig. 7. p140Cap expression is lost in aggressive human breast cancers. In the histogram we reported the number of tumours positive (white) or negative (grey) for p140Cap expression according to tumour grade (low grade G1/G2, high grade G3), number of mitosis 10/10 HPS (M1 Mitosis < 10, M2 Mitosis>10), Ki67 proliferation index (Ki67+>24% , Ki67- <24%),

infiltration in lymph nodes (Node+, Node-), EGFR staining (EGFR+), E-Cadherin staining

Interestingly, 94.8% of aggressive G3 tumours, 87% of the Node +, 86.5% of tumours with a mitosis major number of 10/10HPF, and 76% of highly proliferative tumours (revealed by Ki67 staining), lose p140Cap expression. Moreover, none of the E-cadherin negative and EGFR positive tumours express p140Cap, suggesting mutually exclusive correlation between EGFR and p140Cap expression (Figure 7) (Damiano *et al*., 2010). Therefore, although limited, these data point out that only low grade breast tumors express p140Cap. Further analysis is required to draw a general picture of the relevance of p140Cap in human breast cancers, and to delineate a potential use of p140Cap as a diagnostic and prognostic

Estrogen Receptor staining (ER-, ER+), Progesterone Receptor staining (PR-, PR+),

(E-Cad-). The figure is modified from Damiano *et al*., 2010.

Stefano *et al.*, 2004; Jaworski *et al.*, 2009).

**4.3 140Cap in human breast cancer** 

malignancy.

factor.
