Περίληψη:
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous
regulators of matrix metalloproteinases (MMPs). They are believed to
possess several distinct cellular functions, particularly the
contradictory activities of inhibiting MMPs and promoting tumor cell
growth. Immunohistochemistry was performed to detect TIMP-2 protein in
136 infiltrative breast carcinomas. TIMP-2 protein was analyzed in
parallel with clinicopathologic features (tumor size, histologic type,
nuclear and histologic grade, stage), patients’ overall survival and ER,
PR, Ki-67, topo IIalpha, c-erbB-2, p53 and bcl-2 proteins. Statistical
analysis was performed using univariate and multivariate models
analysis. Immunoreactivity for TIMP-2 was observed in cancer cells and
stromal. fibroblasts in 106 (77.94%) and 104 (76.47%) of 136 cases,
respectively. TIMP-2 protein expression in stromal fibroblasts showed a
statistically significant inverse correlation with tumor size (P =
.014). An inverse correlation was also observed between TIMP-2
epithelial immunoreactivity and nuclear and histologic grade (P = .036
and P = .007, respectively). TIMP-2 protein reactivity showed
statistically significant positive associations with topo IIalpha and
bcl-2 in stromal and cancer cells, respectively (P = .032 and P = .001,
respectively). TIMP-2 protein expression in cancer and stromal cells was
associated with better patients’ overall survival (P = .002 and P =
.038, respectively). When evaluated by the Cox’s proportional hazard
regression model, this association was further established, but only as
far as TIMP-2 expression in tumor epithelium was concerned (P = .019).
Our results support the multifunctional potential of TIMP-2 through its
correlation on the one hand to a favorable outcome, due to its MMP
inhibitory activity and on the other to topo IIalpha contributing to its
growth factor activity.
Συγγραφείς:
Nakopoulou, L
Katsarou, S
Giannopoulou, I
Alexandrou, P and
Tsirmpa, I
Panayotopoulou, E
Mavrommatis, J
Keramopoulos, A
