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Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis.

Rosin G, de Boniface J, Karthik GM, Frisell J, Bergh J, Hartman J - Br. J. Cancer (2014)

Bottom Line: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy.Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer.Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14183 Huddinge, Sweden.

ABSTRACT

Background: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.

Methods: We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.

Results: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.

Conclusions: Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

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Related in: MedlinePlus

ER expression among different age groups and histological grades. (A) ERα positivity decreased with higher Elston–Ellis histological grade (white; P<0.001, N=80, 168, and 71). ERβcx showed a similar trend, however not significant (black; P=0.23, N=80, 163, and 69). ERβ1 was equally distributed among all three grades (grey; P=0.771, N=82, 163, and 68). (B) Patients were divided into four different age groups according to age at diagnosis, <40, 40–54, 55–64, and ⩾65 years. ERα (white) positivity was lowest in the youngest age group and increased with age (P=0.011, N=10, 96, 139, and 75). A similar trend was seen with ERβcx (black), however not reaching significance (P=0.062, N=11, 93, 135, and 73). ERβ1 was equally distributed along all age groups (grey; P=0.221, N=11, 93, 137, and 74). Numbers above bars reflect percentage of positive tumours.
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fig1: ER expression among different age groups and histological grades. (A) ERα positivity decreased with higher Elston–Ellis histological grade (white; P<0.001, N=80, 168, and 71). ERβcx showed a similar trend, however not significant (black; P=0.23, N=80, 163, and 69). ERβ1 was equally distributed among all three grades (grey; P=0.771, N=82, 163, and 68). (B) Patients were divided into four different age groups according to age at diagnosis, <40, 40–54, 55–64, and ⩾65 years. ERα (white) positivity was lowest in the youngest age group and increased with age (P=0.011, N=10, 96, 139, and 75). A similar trend was seen with ERβcx (black), however not reaching significance (P=0.062, N=11, 93, 135, and 73). ERβ1 was equally distributed along all age groups (grey; P=0.221, N=11, 93, 137, and 74). Numbers above bars reflect percentage of positive tumours.

Mentions: A cut-off of 10% was used to distinguish ER-positive from ER-negative tumours. As shown in Figure 1A, the percentage of ERα-positive tumours increased significantly with lower Elston–Ellis histological grade (P<0.001). ERβcx positivity followed a similar pattern but without reaching statistical significance (P=0.23). ERβ1, however, had an equal distribution in all tumour grades (P=0.771). Patients were divided into four age groups: <40 years (N=12), 40–54 years (N=104), 55–64 years (N=141) and ⩾65 years (N=81), to study age-related changes in ER positivity. As shown in Figure 1B, there was a significant increase in ERα-positive tumours with increasing age (P=0.011). There was a similar but non-significant trend for ERβcx positivity (P=0.062) with increased age category. Again ERβ1 showed a different expression pattern, where the positive tumours were equally distributed among all age groups (P=0.22).


Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis.

Rosin G, de Boniface J, Karthik GM, Frisell J, Bergh J, Hartman J - Br. J. Cancer (2014)

ER expression among different age groups and histological grades. (A) ERα positivity decreased with higher Elston–Ellis histological grade (white; P<0.001, N=80, 168, and 71). ERβcx showed a similar trend, however not significant (black; P=0.23, N=80, 163, and 69). ERβ1 was equally distributed among all three grades (grey; P=0.771, N=82, 163, and 68). (B) Patients were divided into four different age groups according to age at diagnosis, <40, 40–54, 55–64, and ⩾65 years. ERα (white) positivity was lowest in the youngest age group and increased with age (P=0.011, N=10, 96, 139, and 75). A similar trend was seen with ERβcx (black), however not reaching significance (P=0.062, N=11, 93, 135, and 73). ERβ1 was equally distributed along all age groups (grey; P=0.221, N=11, 93, 137, and 74). Numbers above bars reflect percentage of positive tumours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150283&req=5

fig1: ER expression among different age groups and histological grades. (A) ERα positivity decreased with higher Elston–Ellis histological grade (white; P<0.001, N=80, 168, and 71). ERβcx showed a similar trend, however not significant (black; P=0.23, N=80, 163, and 69). ERβ1 was equally distributed among all three grades (grey; P=0.771, N=82, 163, and 68). (B) Patients were divided into four different age groups according to age at diagnosis, <40, 40–54, 55–64, and ⩾65 years. ERα (white) positivity was lowest in the youngest age group and increased with age (P=0.011, N=10, 96, 139, and 75). A similar trend was seen with ERβcx (black), however not reaching significance (P=0.062, N=11, 93, 135, and 73). ERβ1 was equally distributed along all age groups (grey; P=0.221, N=11, 93, 137, and 74). Numbers above bars reflect percentage of positive tumours.
Mentions: A cut-off of 10% was used to distinguish ER-positive from ER-negative tumours. As shown in Figure 1A, the percentage of ERα-positive tumours increased significantly with lower Elston–Ellis histological grade (P<0.001). ERβcx positivity followed a similar pattern but without reaching statistical significance (P=0.23). ERβ1, however, had an equal distribution in all tumour grades (P=0.771). Patients were divided into four age groups: <40 years (N=12), 40–54 years (N=104), 55–64 years (N=141) and ⩾65 years (N=81), to study age-related changes in ER positivity. As shown in Figure 1B, there was a significant increase in ERα-positive tumours with increasing age (P=0.011). There was a similar but non-significant trend for ERβcx positivity (P=0.062) with increased age category. Again ERβ1 showed a different expression pattern, where the positive tumours were equally distributed among all age groups (P=0.22).

Bottom Line: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy.Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer.Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14183 Huddinge, Sweden.

ABSTRACT

Background: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.

Methods: We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.

Results: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.

Conclusions: Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

Show MeSH
Related in: MedlinePlus