Phospholipase C-γ immunostaining in human breast carcinoma: Clinical significance and correlations with protease and growth-factor receptor species

Daniel W. Visscher, Fazlul H. Sarkar, Timothy C. Kusinic, Rafael Fridman, Mousumi Banerjee, Kaladhar B. Reddy

Research output: Contribution to journalArticle

Abstract

Cryostat sections of 73 invasive breast carcinomas were immunostained with a rabbit polyclonal antibody to phosphoinositide-specific phospholipase C-γ (PLC-γ), an enzyme that mediates signal transduction in tyrosine kinase growth-factor pathways. Degree of immunoreactivity was then correlated with clinicopathologic data (stage, ER status, recurrence) and immunostaining for tyrosine kinase growth-factor receptors (EGFR, ERBB-2) as well as selected 'invasion-associated' proteases (cathepsin D, urokinase plasminogen activator, matrix metalloproteinases 2 and 9 [MMP-2, MMP-9]). Neoplastic epithelial populations were PLC-γ immunoreactive in 95% of tumors although staining was focally distributed (in <50% of cells) in 51% of positive cases. Forty-four percent also exhibited immunostaining of peritumoral, spindle- shaped cells (i.e., fibroblasts, endothelium, inflammatory cells). The degree of PLC-γ immunoreactivity in neoplastic epithelium was not significantly correlated with clinicopathologic features, growth factor receptor overexpression, or protease immunostaining. Stromal cell PLC-γ staining, however, was significantly associated with stromal cell immunoreactivity for cathepsin D (p = 0.03), urokinase plasminogen activator (p = 0.01), and MMP- 2 (p = 0.04). Disease recurrences were also more frequent in tumors with stroma/spindle cell PLC-γ immunoreactivity (66% vs. 41%, p = 0.04). We conclude that PLC-γ immunostaining, compatible with increased tyrosine kinase pathway signaling activity, is observed not only in a high proportion of neoplastic breast epithelial populations but also in accompanying stromal cell populations in a significant number of cases. Concordance with protease immunoreactivity among peritumoral stromal cells suggests that tyrosine kinase signaling may participate in protease elaboration in vivo, possibly conferring aggressive clinical behavior.

Original languageEnglish (US)
Pages (from-to)350-356
Number of pages7
JournalBreast Journal
Volume3
Issue number6
DOIs
StatePublished - Jan 1 1997

Keywords

  • Breast carcinoma
  • Phospholipase C-γ
  • Proteases

ASJC Scopus subject areas

  • Internal Medicine
  • Surgery
  • Oncology

Fingerprint Dive into the research topics of 'Phospholipase C-γ immunostaining in human breast carcinoma: Clinical significance and correlations with protease and growth-factor receptor species'. Together they form a unique fingerprint.

  • Cite this