title: Overexpression of activated phospholipase Cγ1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy.
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.
authors: Department of Biomedical Sciences, University G. D'Annunzio, Chieti, Italy.
authors: Rossano
authors: R
authors: Lattanzio
authors: Marco
authors: M
authors: Marchisio
authors: Rossana
authors: R
authors: La Sorda
authors: Nicola
authors: N
authors: Tinari
authors: Marco
authors: M
authors: Falasca
authors: Saverio
authors: S
authors: Alberti
authors: Sebastiano
authors: S
authors: Miscia
authors: Cristiana
authors: C
authors: Ercolani
authors: Anna
authors: A
authors: Di Benedetto
authors: Letizia
authors: L
authors: Perracchio
authors: Elisa
authors: E
authors: Melucci
authors: Stefano
authors: S
authors: Iacobelli
authors: Marcella
authors: M
authors: Mottolese
authors: Pier Giorgio
authors: PG
authors: Natali
authors: Mauro
authors: M
authors: Piantelli
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051966:Phospholipase C gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D051966:Phospholipase C gamma