title: Stromal expression of ALDH1 in human breast carcinomas indicates reduced tumor progression.
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.
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Natalia
authors: N
authors: Bednarz-Knoll
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Paulina
authors: P
authors: Nastały
authors: Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
authors: Anna
authors: A
authors: Żaczek
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: MaÅ Gorzata
authors: MG
authors: Stoupiec
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Sabine
authors: S
authors: Riethdorf
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Harriet
authors: H
authors: Wikman
authors: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Volkmar
authors: V
authors: Müller
authors: Bank of Frozen Tissues & Genetic Specimens, Medical University of Gdańsk, Gdańsk, Poland.|Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk, Poland.
authors: Jarosław
authors: J
authors: Skokowski
authors: Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
authors: Jolanta
authors: J
authors: Szade
authors: Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
authors: Aleksandra
authors: A
authors: Sejda
authors: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
authors: Marzena
authors: M
authors: Wełnicka-Jaśkiewicz
authors: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Klaus
authors: K
authors: Pantel
mesh_terms: D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000601:surgery; D002277:Carcinoma / Q000378:metabolism* / Q000601:surgery; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005858:Germany; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000166:cytology; D011044:Poland; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology; D046888:Tissue Array Analysis; D014212:Tretinoin / Q000737:chemistry; D000097382:CD68 Molecule
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D007527:Isoenzymes; D050697:Retinal Dehydrogenase; D014212:Tretinoin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C510223:ALDH1A1 protein, human
keywords: ALDH1; breast cancer; intra-tumoral stroma; tumor progression; tumor-stroma interactions