Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer

Department of Pathology, Turku University Hospital, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.
British Journal of Cancer (Impact Factor: 4.82). 08/2008; 99(2):335-40. DOI: 10.1038/sj.bjc.6604475
Source: PubMed

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.

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    • "Since in the breast cancer the PTTG1 is showing opposite expression pattern of pathway analogues such as securin [28], its detection could be of great clinical importance, being informative for the tumor proliferative capacity and very likely the simultaneous presence of the p53 oncogene mutation pointing towards worse prognosis, shorter time to relapse, and disease progression. In our group only one patient had low proliferation index being insufficient for the speculation, but the immunoreactivity in the metastatic cells allows us to state the presence of the evidence regarding the coexistence of PTTG1 and more aggressive tumor pheno- types. "
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    ABSTRACT: Despite the advances that have been made in the fields of molecular and cell biology, there is still considerable debate explaining how the breast cancer cells progress through carcinogenesis and acquire their metastatic ability. The lack of preventive methods and effective therapies underlines the pressing need to identify new biomarkers that can aid early diagnosis and may be targets for effective therapeutic strategies. In this study we explore the pituitary tumor-transforming gene 1 (PTTG1) expression in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Three human cell lines, 184B5 derived from normal mammary epithelium, HCC70 from a primary ductal carcinoma, and MDA-MB-361 from a breast metastasis, were used for quantifying PTTG1 mRNA expression. The PTTG1 immunohistochemical expression was carried out on specimens taken from eight patients with invasive ductal breast cancer who underwent surgical treatment and followup for five years retrospectively selected. The study demonstrated that PTTG1 is expressed gradually in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Our findings suggest that the immunohistochemical evaluation of PTTG1 expression might be a powerful biomarker of recognition and quantification of the breast cancer cells in routine pathological specimens and a potential target for developing an effective immunotherapeutic strategy for primary and metastatic breast cancer.
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    • "The observed average level of securin immunopositivity in our present results differs from that of our previous study (Talvinen et al, 2008). The obvious explanations lie in the different patient selection procedure and histological material. "
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