#1048
Background: Lymphocyte infiltration (LI) is often seen in breast cancer and has been suggested as a marker of host antitumor immune response but its importance remains controversial. A positive correlation of Her2 amplification/overexpression and LI has been described which was associated with a more favorable outcome. In rapidly proliferating tumors LI is a good prognostic indicator correlating with lymph node negativity, smaller tumor size, lower grade. However the impact of monocytes, B- and T-lymphocytes on prognosis are still a matter of debate.
 Material and Methods: A database of 2110 primary invasive breast cancer samples from 14 microarray datasets was established. Only Affymetrix HG-U133A microarrays were included for full comparability. Feature reduction was achieved by generating metagenes from genes with strong correlation in unsupervised clustering. The relationship of the five major metagenes with different cell types in the sample as well as differentiation programs/pathways associated with specific expression profiles was analyzed.
 Results: A large cluster of approximately 600 genes with functions in immune cells was consistently obtained in all datasets. The redundant information from several ProbeSets allowed the construction of robust metagenes which can be used as surrogate markers for the amount of different immune cell types in the breast cancer sample. However, rather complex relationships of these immunological metagenes with standard parameters of the tumors were observed. When different subgroups of tumors were analyzed for disease free survival the IgG metagene as a surrogate marker for B cells had no significant prognostic value. In contrast high expression of the T cell surrogate marker (LCK metagene) was beneficial among all subgroups of ER-negative tumors. Moreover a positive prognostic value of LCK metagene expression was also revealed for those ER-positive tumors with a Her2 overexpression. In addition a trend for a better response to neoadjuvant chemotherapy was detected for those ER negative tumors associated with lymphocyte infiltration as deduced from high expression of both IgG and LCK metagenes.
 Conclusions: Tumor associated lymphocytes could represent an anti tumor response but on the other hand they might promote tumor progression by shifting the cytokine milieu toward angiogenic factors, inflammatory cytokines and matrix metallo-proteinases. Thus it is crucial to precisely define the specific subtypes of immune cells which are associated with the tumor. Our results demonstrate that this task can be accomplished by a detailed analysis of the expression of metagenes. These surrogate markers define subgroups of tumors with different prognosis.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1048.
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