Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy

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 associa...

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Main Authors: Lattanzio, R., Marchisio, M., La Sorda, R., Tinari, N., Falasca, Marco, Alberti, S., Miscia, S., Ercolani, C., Di Benedetto, A., Perracchio, L., Melucci, E., Iacobelli, S., Mottolese, M., Natali, P., Piantelli, M.
Format: Journal Article
Published: 2013
Online Access:http://hdl.handle.net/20.500.11937/43634
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author Lattanzio, R.
Marchisio, M.
La Sorda, R.
Tinari, N.
Falasca, Marco
Alberti, S.
Miscia, S.
Ercolani, C.
Di Benedetto, A.
Perracchio, L.
Melucci, E.
Iacobelli, S.
Mottolese, M.
Natali, P.
Piantelli, M.
author_facet Lattanzio, R.
Marchisio, M.
La Sorda, R.
Tinari, N.
Falasca, Marco
Alberti, S.
Miscia, S.
Ercolani, C.
Di Benedetto, A.
Perracchio, L.
Melucci, E.
Iacobelli, S.
Mottolese, M.
Natali, P.
Piantelli, M.
author_sort Lattanzio, R.
building Curtin Institutional Repository
collection Online Access
description 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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institution Curtin University Malaysia
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publishDate 2013
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spelling curtin-20.500.11937-436342017-09-13T13:39:38Z Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy Lattanzio, R. Marchisio, M. La Sorda, R. Tinari, N. Falasca, Marco Alberti, S. Miscia, S. Ercolani, C. Di Benedetto, A. Perracchio, L. Melucci, E. Iacobelli, S. Mottolese, M. Natali, P. Piantelli, M. 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. 2013 Journal Article http://hdl.handle.net/20.500.11937/43634 10.1002/ijc.27751 unknown
spellingShingle Lattanzio, R.
Marchisio, M.
La Sorda, R.
Tinari, N.
Falasca, Marco
Alberti, S.
Miscia, S.
Ercolani, C.
Di Benedetto, A.
Perracchio, L.
Melucci, E.
Iacobelli, S.
Mottolese, M.
Natali, P.
Piantelli, M.
Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
title Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
title_full Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
title_fullStr Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
title_full_unstemmed Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
title_short Overexpression of activated phospholipase C?1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
title_sort overexpression of activated phospholipase c?1 is a risk factor for distant metastases in t1-t2, n0 breast cancer patients undergoing adjuvant chemotherapy
url http://hdl.handle.net/20.500.11937/43634