Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer

Abstract

We introduce a new proliferation marker, securin (pituitary tumour-transforming 1 (PTTG1)), analysed in invasive ductal breast carcinomas by cDNA microarrays and immunohistochemistry. In cDNA microarray of a total of 4000 probes of genes, securin was revealed with a significant change in expression among the several proliferation-related genes studied. The value of securin as a proliferation marker was verified immunohistochemically (n=44) in invasive ductal breast cancer. In follow-up analyses of the sample of patients, the prognostic value of securin was compared with the established markers of breast cancer proliferation, Ki-67 and mitotic activity index (MAI). Our results of a small sample of patients suggest that low securin expression identifies a distinct subgroup of more favourable outcome among patients with high Ki-67 immunoexpression or high MAI. In univariate analysis of Cox's regression, 10-unit increment of securin immunopositivity was associated with a 2.3-fold overall risk of death due to breast cancer and a 7.1-fold risk of death due to breast cancer in the sample of patients stratified according to the cutoff points of 10 and 20% of securin immunopositivity. We suggest that securin immunostaining is a promising and clinically applicable proliferation marker. The finding urges further prognostic studies with a large sample of patients.

Figure 1

Securin immunohistochemistry in invasive ductal breast cancer. The bar represents 50 μm.

Figure 2

(A–C) Scatter plots with regression lines demonstrate differences in intermethod consistency between MAI and Ki-67 immunohistochemistry (A), securin immunohistochemistry and MAI (B), and securin and Ki-67 immunohistochemistry (C) for invasive ductal breast cancer cases (n=44).

Figure 3

Kaplan–Meier curves of securin immunohistochemistry distinguish patients with low (<10% securin immunopositivity), intermediate (10–20% securin immunopositivity) and high (>20% securin immunopositivity) risk of death due to breast cancer (n=44) (P=0.0112).