TIF1γ interferes with TGFβ1/SMAD4 signaling to promote poor outcome in operable breast cancer patients

Autor: Isabelle Treilleux, Thomas Bachelot, Jonathan Lopez, Thibaut Goulvent, Mathieu Deygas, Emilie Lavergne, Nicolas Chopin, Nicolas Carrabin, Germain Gillet, Sylvie Chabaud, Ruth Rimokh, Laurent Fattet, Loay Kassem
Přispěvatelé: Clinical Oncology Department, Cairo University - Faculty of Medicine, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], INSERM, CNRS, Ligue Nationale contre le Cancer (Savoie, grant to RR), Fondation ARC (Association pour la Recherche sur le Cancer, Novartis oncology (research grant to LK), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Duchange, Nathalie
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: BMC Cancer
BMC Cancer, BioMed Central, 2015, 15, pp.453. ⟨10.1186/s12885-015-1471-y⟩
BMC Cancer, 2015, 15, pp.453. ⟨10.1186/s12885-015-1471-y⟩
ISSN: 1471-2407
Popis: Background The Transforming growth factor β (TGFβ) signaling has a paradoxical role in cancer development and outcome. Besides, the prognostic significance of the TGFβ1, SMAD4 in breast cancer patients is an area of many contradictions. The transcriptional intermediary factor 1γ (TIF1γ) is thought to interact with the TGFβ/SMAD signaling through different mechanisms. Our study aims to define the prognostic significance of TGFβ1, SMAD4 and TIF1γ expression in breast cancer patients and to detect possible interactions among those markers that might affect the outcome. Methods Immunohistochemistry was performed on tissue microarray (TMA) blocks prepared from samples of 248 operable breast cancer patients who presented at Centre Léon Bérard (CLB) between 1998 and 2001. The intensity and the percentage of stained tumor cells were integrated into a single score (0–6) and a cutoff was defined for high or low expression for each marker. Correlation was done between TGFβ1, SMAD4 and TIF1γ expression with the clinico-pathologic parameters using Pearson’s chi-square test. Kaplan-Meier method was used to estimate distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) and the difference between the groups was evaluated with log-rank test. Results 223 cases were assessable for TIF1γ, 204 for TGFβ1 and 173 for SMAD4. Median age at diagnosis was 55.8 years (range: 27 to 89 years). Tumors were larger than 20 mm in 49.2 % and 45.2 % had axillary lymph node (LN) metastasis (N1a to N3). 19.4 % of the patients had SBR grade I tumors, 46.8 % grade II tumors and 33.9 % grade III tumors. ER was positive in 85.4 %, PR in 75.5 % and Her2-neu was over-expressed in 10 % of the cases. Nuclear TIF1γ, cytoplasmic TGFβ1, nuclear and cytoplasmic SMAD4 stainings were high in 35.9 %, 30.4 %, 27.7 % and 52.6 % respectively. TIF1γ expression was associated with younger age (p = 0.006), higher SBR grade (p
Databáze: OpenAIRE
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