Evaluation of the prognostic significance of HER family mRNA expression in high-risk early XXXX : a Hellenic Cooperative Oncology Group (HeCOG) validation study.

@entity1 @entity0 @entity7514 @entity5 @entity470 @entity12251 @entity406 @entity982 @entity1349 @entity1722
BACKGROUND: The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early @entity0 , as a validation analysis of another previously published HeCOG study. METHODS: RNA was extracted from 663 @entity406 -fixed @entity982 -embedded (FFPE) @entity5 tissue samples of high-risk early @entity0 @entity1 enrolled in the randomized HE10/00 trial. Relative mRNA expression of all four HER family members was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: In compliance with our previous study, the overall agreement between qRT-PCR and IHC/FISH for @entity1722 status determination was good (69%). Likewise, the overall concordance between qRT-PCR and IHC for @entity470 status was high (81%). In line with our previously reported data, we demonstrated a positive association between @entity1722 and @entity7514 mRNA expression. Similarly, mRNA expression of @entity7514 and @entity12251 was positively associated with each other and negatively associated with @entity470 . Regarding relationships with clinico-pathological parameters, our findings are also in agreement with our previous results. Generally, increased @entity470 and @entity1722 mRNA expression was related to unfavorable, whereas high @entity7514 and @entity12251 mRNA expression was associated with favorable clinico-pathological parameters. In univariate analysis, no significant association between @entity470 , @entity1722 and @entity7514 mRNA expression and @entity1349 ( @entity1349 ) or disease-free survival (DFS) was demonstrated. However, high @entity470 protein expression was associated with significantly shorter @entity1349 (log-rank, p = 0.015). In compliance with our previously published data, increased @entity12251 mRNA expression had a significantly favorable prognostic value in terms of @entity1349 (p = 0.044) and DFS (p = 0.047). In multivariate analysis, among all HER receptors, only @entity470 protein expression was found to affect @entity1349 (Wald's p = 0.028) and DFS (p = 0.015) independently. Concerning the combined expression of all four HER family receptors, the combination of high @entity470 , high @entity1722 , low @entity7514 and low @entity12251 mRNA expression was associated with a trend for shorter @entity1349 (log-rank, p = 0.065) and significantly worse DFS (p = 0.033), compared with all other co-expression profiles. CONCLUSIONS: These data indicate that qRT-PCR may represent a valid alternative method for evaluating the expression of HER family members in FFPE @entity0 tissue samples. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609001036202.
