MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers

Abstract

Metastasis associated antigen 1 (MTA1) is a recently identified candidate metastasis-associated gene that plays an important role in tumorigenesis and tumor aggressiveness, especially tumor invasiveness and metastasis. We analyzed the relationship between MTA1 expression and variable clinicopathological features and characterized its role in tumor angiogenesis in human breast cancers. Two hundred and sixty-three breast cancer cases that successfully underwent surgery at Hanyang University Hospital (Seoul, Korea) between January 1989 and December 1997 were enrolled. MTA1 expression was observed by immunohistochemical staining and correlated with intratumoral microvessel density (MVD) and other clinicopathological parameters. MTA1 overexpression correlated significantly with higher tumor grade (grades 1 and 2 vs grade 3, P = 0.009). However, MTA1 expression did not correlate with tumor stage, status of estrogen and progesterone receptors, or axillary lymph node metastasis. Interestingly, MTA1 expression was found to correlate significantly with tumor MVD (P = 0.002). Survival analysis did not show a significant difference between MTA1 overexpression and poorer survival. In conclusion, MTA1 overexpression was found to be closely associated with higher tumor grade and increased tumor angiogenesis. These findings suggest MTA1 as a predictor of aggressive phenotype and a possible target molecule for anti-angiogenic drugs in breast cancer treatment.

Figure 1

(a) Immunohistochemical staining for metastasis associated antigen 1 (MTA1), normal duct and lobule of breast tissue shows generally negative staining. Representative sections of (b) weak, (c) moderate and (d) strong positive staining for MTA1 expression. MTA1 expression is localized in the nucleus of tumor cells.

Figure 2

(a) Metastasis associated antigen 1 (MTA1) and (c) CD34 staining in serial sections showed weak expression of MTA1 in association with low microvessel density. (b) MTA1 and (d) CD34 staining in a tumor with strong MTA1 expression and abundant microvessels.

Figure 3

Analysis of subgroups with negative or weak (low) and moderate or strong (high) metastasis associated antigen 1 (MTA1) expression is presented by bars. Tumors with higher MTA1 expression showed significantly higher microvessel density than tumors with lower MTA‐1 expression (Mann–Whitney test).

Figure 4

Cumulative survival according to metastasis associated antigen 1 (MTA1) expression in breast cancer patients (Kaplan–Meier method and log‐rank test). Higher MTA1 expression did not correlate with poorer prognosis.