Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray.

• ABSTRACT: BACKGROUND: Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. METHODS: Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. RESULTS: BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P=0.026) and cell membrane specific expression (P=0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. CONCLUSIONS: We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Age Factors

Aged

Antigens

CD46

analysis

Breast Neoplasms

chemistry

mortality

pathology

therapy

Carcinoma

chemistry

mortality

pathology

therapy

Female

Humans

Immediate-Early Proteins

analysis

Immunohistochemistry

Kaplan-Meier Estimate

Ki-67 Antigen

analysis

Middle Aged

Predictive Value of Tests

Proportional Hazards Models

Receptor

Adenosine A1

analysis

Receptor

erbB-2

analysis

Receptors

Adiponectin

analysis

Risk Assessment

Risk Factors

Sweden

epidemiology

Time Factors

Tissue Array Analysis

Treatment Outcome

Tumor Markers

Biological

analysis

Tumor Suppressor Proteins

analysis

Up-Regulation

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