UC Irvine

The purpose of this study was to determine the distribution of and potential significance of laminin 332 (LM332) in breast cancer. Specimens from a population-based cohort (N = 297) from 1994 to 1995 were stained for estrogen receptor (ER), progesterone receptor (PgR), HER2 and the LM332 β3 chain. Seventy-five tumors were LM332-positive and 222 were negative. LM332 β3 stained 16.0% of ER and/or PgR-positive tumors and 73.2% of triple-negative breast cancers (TNBC). Immunoblotting revealed LM332 in TNBC and HER2-positive samples, but not in an ER-positive breast carcinoma or a phyllodes tumor. After 20 years, 172 patients were alive, 43 had died of breast cancer and 82 of other causes. Patients with LM332-positive tumors had significantly worse 5 (P < .0001) and 10-year (P < .05) overall and breast cancer specific survival. Among patients with LM332 β3-expressing and ER/PgR-negative carcinomas, 10-year survival was significantly reduced (P < .0450). In a multivariate analysis LM332-positive patients had significant hazard ratios of 3.9 with 95% confidence intervals (CI) of 2.0-7.7 and 2.2 with 95% CI of 1.3-3.8 for 5 and 10-year overall survival, respectively. Because tumor cell motility is required for metastasis, the effect of LM332 on MDA-MB-231 migration was determined using siRNA. Knockdown of LM332-specific β3 and γ2 chains reduced motility without affecting viability. Our observation that LM332 in breast carcinoma is associated with decreased survival provides evidence that LM332 may have a role in the aggressive phenotype of some breast cancers.