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Hum Pathol. 2018 Dec;82:289-296. doi: 10.1016/j.humpath.2018.08.003. Epub 2018 Aug 17.

Laminin 332 expression and prognosis in breast cancer.

Author information

1
Department of Pathology, Keck School of Medicine, the University of Southern California; Los Angeles, CA, USA; Department of Pathology, University of California, Orange, CA, USA. Electronic address: Philip.Carpenter@med.usc.edu.
2
Department of Epidemiology, University of California, Irvine, CA 92697-7550, USA. Electronic address: aziogas@uci.edu.
3
Department of Pathology, University of California, Orange, CA, USA; Department of Epidemiology, University of California, Irvine, CA 92697-7550, USA. Electronic address: markhamemma@gmail.com.
4
Department of Pathology, University of California, Orange, CA, USA. Electronic address: alegcantillep@gmail.com.
5
Department of Pathology, Keck School of Medicine, the University of Southern California; Los Angeles, CA, USA. Electronic address: ruiyan80@gmail.com.
6
Department of Epidemiology, University of California, Irvine, CA 92697-7550, USA.

Abstract

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.

KEYWORDS:

Breast carcinoma; Immunohistochemistry; Laminin 332; Prognosis; Triple-negative; Tumor cell migration; siRNA

PMID:
30125583
PMCID:
PMC6289632
[Available on 2019-12-01]
DOI:
10.1016/j.humpath.2018.08.003

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