TY - JOUR
T1 - Prognostic impact of thymidine phosphorylase expression in breast cancer - Comparison of microarray and immunohistochemical data
AU - Ruckhäberle, E.
AU - Karn, T.
AU - Engels, K.
AU - Turley, H.
AU - Hanker, L.
AU - Müller, V.
AU - Schmidt, M.
AU - Ahr, A.
AU - Gaetje, R.
AU - Holtrich, U.
AU - Kaufmann, M.
AU - Rody, A.
N1 - Funding Information:
We thank Samira Adel and Katherina Kourtis for expert technical assistance. This work was supported by grants from the Deutsche Krebshilfe, the Margarete Bonifer-Stiftung, Bad Soden, the BANSS-Stiftung, Biedenkopf, the Werner Sack-Stiftung, Essen, and Dr. Robert Pfleger-Stiftung, Bamberg. These foundations had no role in planning of the study and writing of the manuscript.
PY - 2010/2
Y1 - 2010/2
N2 - Contrary findings exist according to the prognostic and predictive impact of thymidine phosphorylase (TP) expression in breast cancer. Goal of our study was to investigate TP expression on the mRNA level by microarray analysis in a large cohort of 1781 breast cancers and to analyse its prognostic impact. Furthermore we compared mRNA expression and immunohistochemical data to explain discrepancies between different studies. The prognostic value of TP mRNA expression was analysed among n = 622 untreated patients. Strong expression in the subgroup of n = 213 ER-negative cancer correlates with improved survival (P = 0.012). In contrast, no difference in survival was detected in the ER-positive group. We also failed to observe a prognostic value of TP mRNA among n = 435 endocrine-treated patients as well as n = 111 CMF-treated patients. In an unsupervised analysis, TP clustered together with genes expressed in immune cells. Moreover, among normal tissues the highest TP mRNA expression was found in tissues of the immune system. The profile of TP expression in breast cancers correlates to a metagene of interferon induction whereas the expression of TP among normal tissues correlates to a metagene for macrophages. When comparing microarray data with immunohistochemistry from the same n = 51 samples, there was no correlation with stained carcinoma cells. In contrast, the correlation with stromal staining was highly significant (P < 0.001). Thus TP mRNA from microarray mainly reflects expression in stromal and immune cells. This could account for discrepant results from mRNA and IHC studies. In conclusion, the tumour infiltrating immune cells seem to be a major source of TP expression and predict a favourable prognosis in ER-negative breast cancer. Our data point to a role of TP in host immune response.
AB - Contrary findings exist according to the prognostic and predictive impact of thymidine phosphorylase (TP) expression in breast cancer. Goal of our study was to investigate TP expression on the mRNA level by microarray analysis in a large cohort of 1781 breast cancers and to analyse its prognostic impact. Furthermore we compared mRNA expression and immunohistochemical data to explain discrepancies between different studies. The prognostic value of TP mRNA expression was analysed among n = 622 untreated patients. Strong expression in the subgroup of n = 213 ER-negative cancer correlates with improved survival (P = 0.012). In contrast, no difference in survival was detected in the ER-positive group. We also failed to observe a prognostic value of TP mRNA among n = 435 endocrine-treated patients as well as n = 111 CMF-treated patients. In an unsupervised analysis, TP clustered together with genes expressed in immune cells. Moreover, among normal tissues the highest TP mRNA expression was found in tissues of the immune system. The profile of TP expression in breast cancers correlates to a metagene of interferon induction whereas the expression of TP among normal tissues correlates to a metagene for macrophages. When comparing microarray data with immunohistochemistry from the same n = 51 samples, there was no correlation with stained carcinoma cells. In contrast, the correlation with stromal staining was highly significant (P < 0.001). Thus TP mRNA from microarray mainly reflects expression in stromal and immune cells. This could account for discrepant results from mRNA and IHC studies. In conclusion, the tumour infiltrating immune cells seem to be a major source of TP expression and predict a favourable prognosis in ER-negative breast cancer. Our data point to a role of TP in host immune response.
UR - http://www.scopus.com/inward/record.url?scp=75149187415&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2009.11.020
DO - 10.1016/j.ejca.2009.11.020
M3 - Journal articles
C2 - 20022486
AN - SCOPUS:75149187415
SN - 0959-8049
VL - 46
SP - 549
EP - 557
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 3
ER -