PubMed · 16327481
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Raphael Sinna, Sebastien Garson, Emmanuel Delay. 2005. Three-dimensional imaging.. https://doi.org/10.1097/01.sap.0000188179.68180.2e
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The transcription factor Forkhead-box A1 (Foxa1), a member of the FOX class of transcription factors, has been implicated in the pathogenesis of lung, esophageal and prostate cancers. We have recently identified transcriptional activation of p27 by FOXA1. In this study, we analyzed the activities and expression pattern of FOXA1 in breast cancer. Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli. In the estrogen receptor (ER)-positive MCF-7 cells, FOXA1 increased p27 promoter activity and inhibited the ER pathway activity. Analysis of FOXA1 expression in breast tissue arrays revealed significantly higher expression in pure ductal carcinomas in situ compared to invasive ductal carcinomas (IDC); and in IDC, high expression of FOXA1 was associated with favorable prognostic factors. Yet, FOXA1 expression was noted in a subset of the ER-negative tumors. Taken together, our findings suggest a growth inhibitory role for FOXA1, and identify it as a novel, potential prognostic factor in breast cancer.
PURPOSE: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. EXPERIMENTAL DESIGN: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization. RESULTS: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with 'basal-like' immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression. CONCLUSIONS: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas.
A simultaneous bilateral back-projection method for 3D dynamic contrast-enhanced (DCE)-MRI of the breasts was developed and evaluated. Using a double-side band modulation of the RF slab excitation pulse, discontinuous volumes that included both breasts were simultaneously selected. The number of slice phase-encoding steps was undersampled by a factor of 2, and the resulting signal aliasing from one volume to the other was removed using SENSE processing. In-plane encoding was performed with an interleaved radial acquisition reconstructed using dynamic k-space-weighted image contrast (KWIC) temporal filtering. Image resolution was 0.5 x 0.5 x 3.0 mm(3) with an effective temporal resolution of 15 s for both breast volumes. Combined with the 2x acceleration from SENSE encoding, this is a 16x acceleration factor over a conventional MR bilateral breast scan. An initial evaluation of these methods was performed on a cohort of women who presented with palpable or mammographically visible breast abnormalities. A total of 73 abnormalities were found in 45 of the 54 bilateral examinations that were performed. In 11 of these cases there was a significant finding in the contralateral breast. DCE images of both breasts can be acquired simultaneously, resulting in high-resolution images as well as rapid sampling of the contrast kinetics.