Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray.
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.
Möllerström
Elin
E
Department of Oncology, Institute of Clinical Sciences, Blå stråket 2, University of Gothenburg, SE-413 45 Göteborg, Sweden. elin.mollerstrom@neuro.gu.se
Kovács
Anikó
A
Lövgren
Kristina
K
Nemes
Szilard
S
Delle
Ulla
U
Danielsson
Anna
A
Parris
Toshima
T
Brennan
Donal J
DJ
Jirström
Karin
K
Karlsson
Per
P
Helou
Khalil
K
D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D051916:Membrane Cofactor Protein / Q000032:analysis; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D043682:Receptor, Adenosine A1 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D054419:Receptors, Adiponectin / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D017874:Immediate-Early Proteins; D019394:Ki-67 Antigen; D051916:Membrane Cofactor Protein; D043682:Receptor, Adenosine A1; D018719:Erb-b2 Receptor Tyrosine Kinases; D054419:Receptors, Adiponectin; D025521:Tumor Suppressor Proteins; C475418:ADIPOR1 protein, human; C497857:CD46 protein, human; C070114:BTG2 protein, human; C508053:ERBB2 protein, human