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Stromal expression of ALDH1 in human breast carcinomas indicates reduced tumor progression
Authors:Natalia Bednarz-Knoll  Paulina Nasta?y  Anna ?aczek  Ma?gorzata Stoupiec  Sabine Riethdorf  Harriet Wikman  Volkmar Müller  Jaros?aw Skokowski  Jolanta Szade  Aleksandra Sejda  Marzena We?nicka-Ja?kiewicz  Klaus Pantel
Abstract:Interactions between cancer cells and microenvironment are emerging issue in tumor progression. Aldehyde dehydrogenase 1 (ALDH1) is a recognized cancer stem cell marker but little is known about its role in intratumoral stroma. Therefore, we focused on ALDH1 expression in tumor-associated stroma of breast carcinomas (BrCa).Stromal and tumoral ALDH1 expression was evaluated immunohistochemically in BrCa and their lymph node metastases (LNMs), and related to clinico-pathological characteristics, patients’ outcome, presence of CD68, HLADR, retinoic acid (RA) in stroma, and selected proteins in tumor cells.ALDH1(+) stromal cells were detected in 53% of 374 BrCa and 61% of 102 LNMs. ALDH1(+) stroma in primary tumor correlated to longer disease-free (p = 0.030), metastasis-free (p = 0.024), and overall survival (p = 0.043) having an independent prognostic impact on DFS (multivariate analysis, p = 0.047). It was associated with concomitant presence of HLA-DR(+) stromal cells and RA in tumor cells (both p < 0.001), and inversely associated with vimentin expression in tumor cells (p = 0.036). ALDH1(+) stroma in LNMs correlated inversely to presence of disseminated tumor cells in patients’ bone marrow (p = 0.014) and was independent prognosticator of shorter DFS and MFS (multivariate analysis, p = 0.004 and p = 0.002, respectively).In conclusion, ALDH1 expression in tumor-associated stromal cells indicates reduced BrCa progression, possibly via RA secretion.
Keywords:breast cancer   ALDH1   intra-tumoral stroma   tumor-stroma interactions   tumor progression
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