Preferential nuclear and cytoplasmic NY-BR-1 protein expression in primary breast cancer and lymph node metastases

Clin Cancer Res. 2006 May 1;12(9):2745-51. doi: 10.1158/1078-0432.CCR-05-2192.

Abstract

Purpose: NY-BR-1 is a recently isolated differentiation antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1 to study the protein expression of NY-BR-1.

Methods: In our immunohistochemical study, NY-BR-1 was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases.

Results: Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity. This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor-positive and lymph node-negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-BR-1 expression is lost with tumor progression. Forty-nine percent of lymph node metastases were NY-BR-1 positive.

Conclusion: This study supports the notion that NY-BR-1 is a differentiation antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Nucleus / genetics
  • Cell Nucleus / pathology
  • Cytoplasm / genetics
  • Cytoplasm / pathology
  • Female
  • Genes, erbB-2
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis*
  • Menopause
  • Microscopy, Confocal
  • Organ Specificity
  • Receptors, Estrogen / analysis

Substances

  • ANKRD30A protein, human
  • Antigens, Neoplasm
  • Receptors, Estrogen