Characterization of genotypic disorders in ERα+ breast cancers by evaluating ERα and TFF1 expression: Is TFF1 a promising predictive biomarker for endocrine therapy?

Abstract

TFF1 is overexpressed in estradiol-dependent invasive breast carcinomas Estrogen Receptor positive (ERα+). However, certain subclasses of ERα+ tumors do not overexpress this protein and present a therapeutic escape from endocrine therapy. This study was conducted to characterize the genotypic disorders of ERα+ breast cancers by quantitative evaluation of intratumoral heterogeneity in ERα and TFF1 expression and to precise the clinical significance of TFF1 overexpression in primary ERα+ mammary invasive ductal carcinomas (IDCs). To evaluate the intratumoral distribution of ERα and TFF1, 60 primary ERα+ IDCs were used and stereological analysis were conducted. The labeling index (LI) and the mean labeling index (MLI) for the two markers overexpression were evaluated. The coefficient of variation (COV) was used to estimate spatial dispersion of markers. Stereological analysis showed that the mean ERα and TFF1 labeling indexes (MLI) showed a heterogeneous distribution of markers in each tumor with rates fluctuating between 21.59% ± 10.18 and 46.91% ± 10.61 for ERα and between 18.73% ± 6.32 and 34.39% ± 8.71 for TFF1. The COV showed values fluctuating between 16.75% and 44.40% for ERα and between 25.3% and 65.7% for TFF1 reflecting an important heterogenous dispersion of ERα and TFF1 protein within the same tumor. This study allowed us a simple quantitative estimation of the phenotypic heterogeneity wich is the reflection of genotypic disorders. Our results showed that ERα+ breast cancers are genetically unstable and can present 2 different phenotypes [ERα+/TFF1+] or [ERα+/TFF1¯]. This genetic instability explains the resistance of these cancers to hormonal therapy.