J Cancer 2014; 5(5):360-367. doi:10.7150/jca.7885

Research Paper

Aldehyde Dehydrogenase1 Immunohistochemical Staining in Primary Breast Cancer Cells Independently Predicted Overall Survival But Did Not Correlate with the Presence of Circulating or Disseminated Tumors Cells

Wendy A. Woodward1✉, Savitri Krishnamurthy2, Ashutosh Lodhi3, Lianchun Xiao4, Yun Gong2, Massimo Cristofanilli5, Thomas A. Buchholz1, Anthony Lucci3

1. Departments of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
2. Departments of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
3. Departments of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
4. Departments of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
5. The Department of Medical Oncology Thomas Jefferson University.

Abstract

Purpose: We hypothesized that aldehyde dehydrogenase 1 (ALDH1) staining in breast cancer tumor cells might be a simple surrogate for the presence of circulating tumor cells (CTCs) or disseminated tumor cells (DTCs).

Experimental Design: Whole tissue primary tumor sections from 121 patients enrolled in a clinical trial assessing CTCs and DTCs at the time of surgery were stained for ALDH1 and scored by a dedicated breast pathologist blinded to outcome. Clinical data was extracted and staining was correlated to clinical variables and outcome by Fisher's exact test, the Log rank test and Cox proportional hazards regression analysis respectively. P < 0.05 was considered significant.

Results: ALDH1 staining in tumor cells was present in 12% of cases (15/121). In univariate analysis, ALDH1 tumor staining predicted worse overall survival (71% vs. 91% at 5 years P = 0.0074) and was an independent predictor on multivariable analysis of worse overall survival, (HR 4.93) after adjusting for stage, ER, grade, LVI, age and neoadjuvant chemotherapy (P = 0.04).

ALDH1 was significantly associated with estrogen receptor (ER) negative (P value = 0.029) primary tumors but not the presence of CTCs or DTCs by multivariate logistic regression. Positive ALDH staining in non-tumor cells of any pattern or morphology was common but did not correlate with CTCs or DTCs, other clinical variables, or outcome.

Conclusion: ALDH1 tumor staining was associated with ER -negative breast cancer and was an independent predictor of OS. However, it did not correlate to putative cancer stem cell surrogates CTCs and/or DTCs.

Keywords: ALDH1, breast cancer, cancer stem cells, circulating tumor cells, disseminated tumor cells, micrometastatic disease.

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How to cite this article:
Woodward WA, Krishnamurthy S, Lodhi A, Xiao L, Gong Y, Cristofanilli M, Buchholz TA, Lucci A. Aldehyde Dehydrogenase1 Immunohistochemical Staining in Primary Breast Cancer Cells Independently Predicted Overall Survival But Did Not Correlate with the Presence of Circulating or Disseminated Tumors Cells. J Cancer 2014; 5(5):360-367. doi:10.7150/jca.7885. Available from http://www.jcancer.org/v05p0360.htm