Cytoplasmic estrogen receptor in breast cancer

Allison W. Welsh, Donald R. Lannin, Gregory S. Young, Mark E. Sherman, Jonine D. Figueroa, N. Lynn Henry, Lisa Ryden, Chungyeul Kim, Richard R. Love, Rachel Schiff, David L. Rimm

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Abstract

Purpose: In addition to genomic signaling, it is accepted that estrogen receptor-α (ERα) has nonnuclear signaling functions, which correlate with tamoxifen resistance in preclinical models. However, evidence for cytoplasmic ER localization in human breast tumors is less established. We sought to determine the presence and implications of nonnuclear ER in clinical specimens. Experimental Design: A panel of ERα-specific antibodies (SP1, MC20, F10, 60c, and 1D5) was validated by Western blot and quantitative immunofluorescent (QIF) analysis of cell lines and patient controls. Then eight retrospective cohorts collected on tissue microarrays were assessed for cytoplasmic ER. Four cohorts were from Yale (YTMA 49, 107, 130, and 128) and four others (NCI YTMA 99, South Swedish Breast Cancer Group SBII, NSABP B14, and a Vietnamese Cohort) from other sites around the world. Results: Four of the antibodies specifically recognized ER by Western and QIF analysis, showed linear increases in amounts of ER in cell line series with progressively increasing ER, and the antibodies were reproducible on YTMA 49 with Pearson correlations (r2 values) ranging from 0.87 to 0.94. One antibody with striking cytoplasmic staining (MC20) failed validation. We found evidence for specific cytoplasmic staining with the other four antibodies across eight cohorts. The average incidence was 1.5%, ranging from 0 to 3.2%. Conclusions: Our data show ERα is present in the cytoplasm in a number of cases using multiple antibodies while reinforcing the importance of antibody validation. In nearly 3,200 cases, cytoplasmic ER is present at very low incidence, suggesting its measurement is unlikely to be of routine clinical value.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalClinical Cancer Research
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2012

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Cytoplasmic and Nuclear Receptors
Estrogen Receptors
Breast Neoplasms
Antibodies
Staining and Labeling
Cell Line
Incidence
Tamoxifen
Cytoplasm
Research Design
Western Blotting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Welsh, A. W., Lannin, D. R., Young, G. S., Sherman, M. E., Figueroa, J. D., Henry, N. L., ... Rimm, D. L. (2012). Cytoplasmic estrogen receptor in breast cancer. Clinical Cancer Research, 18(1), 118-126. https://doi.org/10.1158/1078-0432.CCR-11-1236

Cytoplasmic estrogen receptor in breast cancer. / Welsh, Allison W.; Lannin, Donald R.; Young, Gregory S.; Sherman, Mark E.; Figueroa, Jonine D.; Henry, N. Lynn; Ryden, Lisa; Kim, Chungyeul; Love, Richard R.; Schiff, Rachel; Rimm, David L.

In: Clinical Cancer Research, Vol. 18, No. 1, 01.01.2012, p. 118-126.

Research output: Contribution to journalArticle

Welsh, AW, Lannin, DR, Young, GS, Sherman, ME, Figueroa, JD, Henry, NL, Ryden, L, Kim, C, Love, RR, Schiff, R & Rimm, DL 2012, 'Cytoplasmic estrogen receptor in breast cancer', Clinical Cancer Research, vol. 18, no. 1, pp. 118-126. https://doi.org/10.1158/1078-0432.CCR-11-1236
Welsh AW, Lannin DR, Young GS, Sherman ME, Figueroa JD, Henry NL et al. Cytoplasmic estrogen receptor in breast cancer. Clinical Cancer Research. 2012 Jan 1;18(1):118-126. https://doi.org/10.1158/1078-0432.CCR-11-1236
Welsh, Allison W. ; Lannin, Donald R. ; Young, Gregory S. ; Sherman, Mark E. ; Figueroa, Jonine D. ; Henry, N. Lynn ; Ryden, Lisa ; Kim, Chungyeul ; Love, Richard R. ; Schiff, Rachel ; Rimm, David L. / Cytoplasmic estrogen receptor in breast cancer. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 1. pp. 118-126.
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AU - Ryden, Lisa

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