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A shift from nuclear to cytoplasmic breast cancer metastasis suppressor 1 expression is associated with highly proliferative estrogen receptor-negative breast cancers.

ABSTRACT: To determine breast cancer metastasis suppressor 1 (BRMS1) expression in breast cancers and the efficacy of BRMS1 as a prognostic indicator, BRMS1 expression was assessed in two sets of breast cancer tissues.Epithelial cells from 36 frozen samples of breast cancers and corresponding normal breast were collected by laser capture microdissection and assessed for BRMS1 by quantitative RT-PCR and immunohistochemistry. BRMS1 was also evaluated by immunohistochemistry in a tissue microarray of 209 breast cancers and correlated with indicators of prognosis [estrogen receptor (ER), progesterone receptor (PR), ErbB2, p53, p27(Kip1), Bcl2 and Ki-67].BRMS1 mRNA and protein were higher in 94 and 81%, respectively, of breast cancers than in corresponding normal epithelium. BRMS1 localization was predominantly nuclear, but 60-70% of cancers also exhibited cytoplasmic immunostaining. Breast cancers with lower nuclear than cytoplasmic BRMS1 (nuclear score - cytoplasmic score < or =0; 11% of cancers) had lower ER, lower PR and higher Ki-67 expression. There was also a trend toward poorer overall survival in this group of cancers, but this was only of borderline significance (p = 0.073). In Cox proportional hazards models, loss of nuclear BRMS1 was not a significant predictor of overall survival.Loss of nuclear BRMS1 was associated with ER-negative cancers and a high rate of proliferation, but was not an independent indicator of prognosis.

SUBMITTER: Frolova N

PROVIDER: S-EPMC2749949 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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A shift from nuclear to cytoplasmic breast cancer metastasis suppressor 1 expression is associated with highly proliferative estrogen receptor-negative breast cancers.

Frolova Natalya N Edmonds Mick D MD Bodenstine Thomas M TM Seitz Robert R Johnson Martin R MR Feng Rui R Welch Danny R DR Frost Andra R AR

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20090716 3

<h4>Background/aims</h4>To determine breast cancer metastasis suppressor 1 (BRMS1) expression in breast cancers and the efficacy of BRMS1 as a prognostic indicator, BRMS1 expression was assessed in two sets of breast cancer tissues.<h4>Methods</h4>Epithelial cells from 36 frozen samples of breast cancers and corresponding normal breast were collected by laser capture microdissection and assessed for BRMS1 by quantitative RT-PCR and immunohistochemistry. BRMS1 was also evaluated by immunohistoche ...[more]

PMID: 19609101

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Project description:Early-stage estrogen receptor-positive (ER+) breast cancer (BCa) is the most common type of BCa in the United States. One critical question with these tumors is identifying which patients will receive added benefit from adjuvant chemotherapy. Nuclear pleomorphism (variance in nuclear shape and morphology) is an important constituent of breast grading schemes, and in ER+ cases, the grade is highly correlated with disease outcome. This study aimed to investigate whether quantitative computer-extracted image features of nuclear shape and orientation on digitized images of hematoxylin-stained and eosin-stained tissue of lymph node-negative (LN-), ER+ BCa could help stratify patients into discrete (<10 years short-term vs. >10 years long-term survival) outcome groups independent of standard clinical and pathological parameters. We considered a tissue microarray (TMA) cohort of 276 ER+, LN- patients comprising 150 patients with long-term and 126 patients with short-term overall survival, wherein 177 randomly chosen cases formed the modeling set, and 99 remaining cases the test set. Segmentation of individual nuclei was performed using multiresolution watershed; subsequently, 615 features relating to nuclear shape/texture and orientation disorder were extracted from each TMA spot. The Wilcoxon's rank-sum test identified the 15 most prognostic quantitative histomorphometric features within the modeling set. These features were then subsequently combined via a linear discriminant analysis classifier and evaluated on the test set to assign a probability of long-term vs. short-term disease-specific survival. In univariate survival analysis, patients identified by the image classifier as high risk had significantly poorer survival outcome: hazard ratio (95% confident interval)?=?2.91(1.23-6.92), p?=?0.02786. Multivariate analysis controlling for T-stage, histology grade, and nuclear grade showed the classifier to be independently predictive of poorer survival: hazard ratio (95% confident interval)?=?3.17(0.33-30.46), p?=?0.01039. Our results suggest that quantitative histomorphometric features of nuclear shape and orientation are strongly and independently predictive of patient survival in ER+, LN- BCa.

Dataset Information

A shift from nuclear to cytoplasmic breast cancer metastasis suppressor 1 expression is associated with highly proliferative estrogen receptor-negative breast cancers.

Publications

A shift from nuclear to cytoplasmic breast cancer metastasis suppressor 1 expression is associated with highly proliferative estrogen receptor-negative breast cancers.

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