Expression levels of estrogen receptor beta in conjunction with aromatase predict survival in non-small cell lung cancer - PubMed (original) (raw)

doi: 10.1016/j.lungcan.2011.03.009. Epub 2011 Apr 20.

Diana Marquez, Mohammad Alavi, Erin L Maresh, Li Zhang, Nam Yoon, Steve Horvath, Lora Bagryanova, Michael C Fishbein, David Chia, Richard Pietras, Lee Goodglick

Affiliations

Expression levels of estrogen receptor beta in conjunction with aromatase predict survival in non-small cell lung cancer

Vei Mah et al. Lung Cancer. 2011 Nov.

Abstract

Estrogen signaling pathways may play a significant role in the pathogenesis of non-small cell lung cancers (NSCLC) as evidenced by the expression of aromatase and estrogen receptors (ERα and ERβ) in many of these tumors. Here we examine whether ERα and ERβ levels in conjunction with aromatase define patient groups with respect to survival outcomes and possible treatment regimens. Immunohistochemistry was performed on a high-density tissue microarray with resulting data and clinical information available for 377 patients. Patients were subdivided by gender, age and tumor histology, and survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Neither ERα nor ERβ alone was predictor of survival in NSCLC. However, when coupled with aromatase expression, higher ERβ levels predicted worse survival in patients whose tumors expressed higher levels of aromatase. Although this finding was present in patients of both genders, it was especially pronounced in women ≥ 65 years old, where higher expression of both ERβ and aromatase indicated a markedly worse survival rate than that determined by aromatase alone. Expression of ERβ together with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. Our results suggest treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may be of benefit in some subpopulations of these patients.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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Conflict of interest statement

Conflict of Interest Statement: None declared.

Figures

Figure 1

Figure 1

A-C: representative staining of ERα in bronchial epithelium, adenocarcinoma and squamous carcinoma respectively; D-F: representative staining of ERβ in bronchial epithelium, adenocarcinoma and squamous carcinoma; G-I: representative staining of aromatase in bronchial epithelium, adenocarcinoma and squamous carcinoma; J: barplots of ERα and ERβ in different tumor histologies; K: barplots of ERα and ERβ in different tumor grades show a significant increase in cytoplasmic levels of ERβ with increase in grade.

Figure 1

Figure 1

A-C: representative staining of ERα in bronchial epithelium, adenocarcinoma and squamous carcinoma respectively; D-F: representative staining of ERβ in bronchial epithelium, adenocarcinoma and squamous carcinoma; G-I: representative staining of aromatase in bronchial epithelium, adenocarcinoma and squamous carcinoma; J: barplots of ERα and ERβ in different tumor histologies; K: barplots of ERα and ERβ in different tumor grades show a significant increase in cytoplasmic levels of ERβ with increase in grade.

Figure 1

Figure 1

A-C: representative staining of ERα in bronchial epithelium, adenocarcinoma and squamous carcinoma respectively; D-F: representative staining of ERβ in bronchial epithelium, adenocarcinoma and squamous carcinoma; G-I: representative staining of aromatase in bronchial epithelium, adenocarcinoma and squamous carcinoma; J: barplots of ERα and ERβ in different tumor histologies; K: barplots of ERα and ERβ in different tumor grades show a significant increase in cytoplasmic levels of ERβ with increase in grade.

Fig 2

Fig 2

A: For patients with high aromatase expression (determined by staining intensity above median levels) splitting cytoplasmic ERβ expression at the median level, the Kaplan-Meier survival curve shows significantly worse survival in those patients with high ERβ (hazard ratio = 1.6, p-value = 0.029); B: Using above the 60th percentile as a cutoff to define high aromatase expression, low cytoplasmic ERβ (again median expression level) conferred a slightly better prognosis (p=0.0098, hazard ratio = 1.81).

Fig 2

Fig 2

A: For patients with high aromatase expression (determined by staining intensity above median levels) splitting cytoplasmic ERβ expression at the median level, the Kaplan-Meier survival curve shows significantly worse survival in those patients with high ERβ (hazard ratio = 1.6, p-value = 0.029); B: Using above the 60th percentile as a cutoff to define high aromatase expression, low cytoplasmic ERβ (again median expression level) conferred a slightly better prognosis (p=0.0098, hazard ratio = 1.81).

Fig 3

Fig 3

A: For women with high aromatase expression (staining intensity above the 60th percentile splitting cytoplasmic ERβ expression at the midpoint), the Kaplan-Meier survival curve shows worse survival in those patients with high ERβ (hazard ratio = 2.18, p-value = 0.019); B: For men, findings were similar but slightly weaker (hazard ratio = 2.04, P = 0.030). C: In women 65 and over, the findings were stronger than other population subgroups (p=0.003, hazard ratio = 3.25).

Fig 3

Fig 3

A: For women with high aromatase expression (staining intensity above the 60th percentile splitting cytoplasmic ERβ expression at the midpoint), the Kaplan-Meier survival curve shows worse survival in those patients with high ERβ (hazard ratio = 2.18, p-value = 0.019); B: For men, findings were similar but slightly weaker (hazard ratio = 2.04, P = 0.030). C: In women 65 and over, the findings were stronger than other population subgroups (p=0.003, hazard ratio = 3.25).

Fig 3

Fig 3

A: For women with high aromatase expression (staining intensity above the 60th percentile splitting cytoplasmic ERβ expression at the midpoint), the Kaplan-Meier survival curve shows worse survival in those patients with high ERβ (hazard ratio = 2.18, p-value = 0.019); B: For men, findings were similar but slightly weaker (hazard ratio = 2.04, P = 0.030). C: In women 65 and over, the findings were stronger than other population subgroups (p=0.003, hazard ratio = 3.25).

Fig 4

Fig 4

A: For patients with high cytoplasmic ERβ expression (determined by staining intensity above median levels) splitting aromatase expression at the median level, the Kaplan-Meier survival curve shows significantly worse survival in those patients with aromatase (hazard ratio = 1.47, p-value = 0.001); B: For women with high cytoplasmic ERβ expression, again the Kaplan-Meier survival curve again shows worse survival in those patients with higher aromatase (hazard ratio = 1.49, p-value = 0.013); C: For men, findings were similar but slightly weaker (hazard ratio = 1.38, P = 0.052).

Fig 4

Fig 4

A: For patients with high cytoplasmic ERβ expression (determined by staining intensity above median levels) splitting aromatase expression at the median level, the Kaplan-Meier survival curve shows significantly worse survival in those patients with aromatase (hazard ratio = 1.47, p-value = 0.001); B: For women with high cytoplasmic ERβ expression, again the Kaplan-Meier survival curve again shows worse survival in those patients with higher aromatase (hazard ratio = 1.49, p-value = 0.013); C: For men, findings were similar but slightly weaker (hazard ratio = 1.38, P = 0.052).

Fig 4

Fig 4

A: For patients with high cytoplasmic ERβ expression (determined by staining intensity above median levels) splitting aromatase expression at the median level, the Kaplan-Meier survival curve shows significantly worse survival in those patients with aromatase (hazard ratio = 1.47, p-value = 0.001); B: For women with high cytoplasmic ERβ expression, again the Kaplan-Meier survival curve again shows worse survival in those patients with higher aromatase (hazard ratio = 1.49, p-value = 0.013); C: For men, findings were similar but slightly weaker (hazard ratio = 1.38, P = 0.052).

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