Overexpression of activated phospholipase Cγ1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy

Authors

  • Rossano Lattanzio,

    1. Department of Biomedical Sciences, University “G. D'Annunzio”, Chieti, Italy
    2. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    3. MediaPharma s.r.l., Centre of Excellence on Aging, University “G. D'Annunzio”, Chieti, Italy
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  • Marco Marchisio,

    1. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    2. Department of Medicine and Aging Science, University “G. D'Annunzio”, Chieti, Italy
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  • Rossana La Sorda,

    1. Department of Biomedical Sciences, University “G. D'Annunzio”, Chieti, Italy
    2. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    3. MediaPharma s.r.l., Centre of Excellence on Aging, University “G. D'Annunzio”, Chieti, Italy
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  • Nicola Tinari,

    1. Department of Biomedical Sciences, University “G. D'Annunzio”, Chieti, Italy
    2. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    3. MediaPharma s.r.l., Centre of Excellence on Aging, University “G. D'Annunzio”, Chieti, Italy
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  • Marco Falasca,

    1. Inositide Signalling Group, Centre for Diabetes, The Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom
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  • Saverio Alberti,

    1. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
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  • Sebastiano Miscia,

    1. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    2. Department of Medicine and Aging Science, University “G. D'Annunzio”, Chieti, Italy
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  • Cristiana Ercolani,

    1. Department of Pathology, “Regina Elena” Cancer Institute, Rome, Italy
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  • Anna Di Benedetto,

    1. Department of Pathology, “Regina Elena” Cancer Institute, Rome, Italy
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  • Letizia Perracchio,

    1. Department of Pathology, “Regina Elena” Cancer Institute, Rome, Italy
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  • Elisa Melucci,

    1. Department of Pathology, “Regina Elena” Cancer Institute, Rome, Italy
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  • Stefano Iacobelli,

    Corresponding author
    1. Department of Biomedical Sciences, University “G. D'Annunzio”, Chieti, Italy
    2. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    3. MediaPharma s.r.l., Centre of Excellence on Aging, University “G. D'Annunzio”, Chieti, Italy
    • Department of Biomedical Sciences, University “G. D'Annunzio”, Via dei Vestini, 66100 Chieti, Italy
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    • Tel.: +39-08713556712, Fax: +39-0871-355-6707

  • Marcella Mottolese,

    1. Department of Pathology, “Regina Elena” Cancer Institute, Rome, Italy
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  • Pier Giorgio Natali,

    1. CINBO Laboratories, University “G. D'Annunzio”, Chieti, Italy
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  • Mauro Piantelli,

    1. Department of Biomedical Sciences, University “G. D'Annunzio”, Chieti, Italy
    2. Center of Excellence on Aging, “Università G.D'Annunzio” Foundation, Chieti, Italy
    3. MediaPharma s.r.l., Centre of Excellence on Aging, University “G. D'Annunzio”, Chieti, Italy
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  • on behalf of CINBO (Consorzio Interuniversitario Nazionale per la Bio-Oncologia)

    1. Department of Biomedical Sciences, University “G. D'Annunzio”, Chieti, Italy
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Abstract

Phospholipase Cγ1 (PLCγ1) is highly expressed in several tumors. We have previously reported that both stable and inducible PLCγ1 down-regulation resulted in an almost complete inhibition of breast cancer-derived experimental lung metastasis formation. The aim of our study is to evaluate the association between the expression of PLCγ1 and of PLCγ1 phosphorylated at Tyr1253 (PLCγ1-pY1253) and at Tyr783 (PLCγ1-pY783) with the clinical outcome of patients with node negative, T1/T2 breast cancers. The study groups consisted of 292 (training set) and 122 (validation set) patients presenting with primary unilateral breast carcinoma (T1-T2), with no evidence of nodal involvement and distant metastases. PLCγ1, PLCγ1-pY1253 and PLCγ1-pY783 protein expression were assessed by immunohistochemistry on tissue microarrays and the results correlated with the clinical data using Kaplan–Meier curves and multivariate Cox regression analysis. Tumor cells while expressing variable proportions of cytoplasmic PLCγ1, express PLCγ1-pY1253 and PLCγ1-pY783 predominantly in the nucleus. High expression of PLCγ1, and of its activated forms, is associated with a worse clinical outcome in terms of incidence of distant metastases, and not of local relapse in T1-T2, N0 breast cancer patients undergone adjuvant chemotherapy. PLCγ1 over-expression appears to be a reliable predictive surrogate marker of development of metastases. Thus, targeting PLCγ1 pathways might represent a potential therapeutic approach for the prevention of metastatic disease in breast cancer.

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