Aldehyde dehydrogenase 1-positive cells in axillary lymph node metastases after chemotherapy as a prognostic factor in patients with lymph node-positive breast cancer

Cancer. 2012 Aug 15;118(16):3899-910. doi: 10.1002/cncr.26725. Epub 2011 Dec 16.

Abstract

Background: Aldehyde dehydrogenase 1 (ALDH1)-positive cells exhibit stem-like or progenitor ability and have been considered a clinically important diagnostic and therapeutic target in patients with breast cancer. In this study, the authors evaluated responsiveness to chemotherapy of ALDH1-positive cells in primary and metastatic lesions and its relation to prognosis for patients with lymph node-positive breast cancer.

Methods: In total, 115 patients who had breast cancer with cytologically confirmed lymph node metastases and who underwent surgery after neoadjuvant chemotherapy (NAC) were evaluated. By using ALDH1 immunohistochemistry in core-needle biopsy specimens of the primary tumor, cytology samples of axillary lymph nodes before NAC, and pathologic samples of each after NAC, the clinical significance of ALDH1-positive cell status was evaluated in primary and metastatic lesions before and after NAC.

Results: The presence of ALDH1-positive cancer cells, but not ALDH1-negative cancer cells, in primary and metastatic lesions after NAC was associated with a worse prognosis. In multivariate analysis, only ALDH1-positive cells in metastatic lesions after NAC correlated with overall survival. The responsiveness of ALDH1-positive cells to chemotherapy differed between primary and metastatic lesions, and the findings indicated that ALDH1-positive cells in metastatic lesions after NAC may clinically precede those in the primary lesion.

Conclusions: The responsiveness of ALDH1-positive cells to chemotherapy in primary and metastatic lesions and its prognostic significance were clarified in patients with breast cancer. The authors concluded that ALDH1-positive status may represent a surrogate marker as a new concept in patients with lymph node-positive breast cancer.

MeSH terms

  • Aldehyde Dehydrogenase 1 Family
  • Axilla
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Isoenzymes / metabolism*
  • Lymph Nodes / enzymology
  • Lymphatic Metastasis / pathology
  • Middle Aged
  • Retinal Dehydrogenase / metabolism*

Substances

  • Isoenzymes
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase