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

Möllerström E, Kovács A, Lövgren K, Nemes S, Delle U, Danielsson A, Parris T, Brennan DJ, Jirström K, Karlsson P, Helou K - BMC Cancer (2010)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Institute of Clinical Sciences, Blå stråket 2, University of Gothenburg, SE-413 45 Göteborg, Sweden. elin.mollerstrom@neuro.gu.se

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.

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Variation of the predictive power depending on survival time. The new Cox-regression model containing BTG2 expression, HER2 expression, patient age and Ki67 expression performed better, i.e. revealed higher prediction accuracy, than a Cox-regression model containing the currently used prognostic markers that gained statistical significance (HER2 expression, and patient age). This difference in predictive power was stable, independent of survival time.
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Figure 5: Variation of the predictive power depending on survival time. The new Cox-regression model containing BTG2 expression, HER2 expression, patient age and Ki67 expression performed better, i.e. revealed higher prediction accuracy, than a Cox-regression model containing the currently used prognostic markers that gained statistical significance (HER2 expression, and patient age). This difference in predictive power was stable, independent of survival time.

Mentions: The multivariate analysis showed that the model containing BTG2 expression had better predictive power than the model built on current classical pathological markers (Table 4). The BTG2 model revealed a C-value of 0.781 compared to the slightly lower C-value of 0.772 for the model of currently used markers. If only the markers displaying statistical significance are used from the model of current prognostic markers (HER2 expression and patient age), a C-value of 0.739 was achieved. Figure 5 shows the classification accuracy of a Cox-regression model based on the current markers compared to the classification accuracy of a new model based on the new markers considered in the present study. Over the whole time-span considered the new markers offer superior classification accuracy. For both the new markers and the old ones the classification accuracy shows a slight decreasing trend with time. The strongest correlation of protein expression were between ADIPOR1 and ADORA1 (k = 0.749) and between BTG2 overall expression and BTG2 cytoplasm expression (k = 0.723) (Figure 6).


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

Möllerström E, Kovács A, Lövgren K, Nemes S, Delle U, Danielsson A, Parris T, Brennan DJ, Jirström K, Karlsson P, Helou K - BMC Cancer (2010)

Variation of the predictive power depending on survival time. The new Cox-regression model containing BTG2 expression, HER2 expression, patient age and Ki67 expression performed better, i.e. revealed higher prediction accuracy, than a Cox-regression model containing the currently used prognostic markers that gained statistical significance (HER2 expression, and patient age). This difference in predictive power was stable, independent of survival time.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902444&req=5

Figure 5: Variation of the predictive power depending on survival time. The new Cox-regression model containing BTG2 expression, HER2 expression, patient age and Ki67 expression performed better, i.e. revealed higher prediction accuracy, than a Cox-regression model containing the currently used prognostic markers that gained statistical significance (HER2 expression, and patient age). This difference in predictive power was stable, independent of survival time.
Mentions: The multivariate analysis showed that the model containing BTG2 expression had better predictive power than the model built on current classical pathological markers (Table 4). The BTG2 model revealed a C-value of 0.781 compared to the slightly lower C-value of 0.772 for the model of currently used markers. If only the markers displaying statistical significance are used from the model of current prognostic markers (HER2 expression and patient age), a C-value of 0.739 was achieved. Figure 5 shows the classification accuracy of a Cox-regression model based on the current markers compared to the classification accuracy of a new model based on the new markers considered in the present study. Over the whole time-span considered the new markers offer superior classification accuracy. For both the new markers and the old ones the classification accuracy shows a slight decreasing trend with time. The strongest correlation of protein expression were between ADIPOR1 and ADORA1 (k = 0.749) and between BTG2 overall expression and BTG2 cytoplasm expression (k = 0.723) (Figure 6).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Institute of Clinical Sciences, Blå stråket 2, University of Gothenburg, SE-413 45 Göteborg, Sweden. elin.mollerstrom@neuro.gu.se

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.

Show MeSH
Related in: MedlinePlus