Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions.

TY - JOUR

T1 - Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions.

AU - Lebeau, Annette

AU - Grob, Tj

AU - Holst, Frederik

AU - Seyedi-Fazlollahi, N

AU - Moch, H

AU - Terracciano, Luigi

AU - Turzynski, A

AU - Choschzick, Matthias

AU - Sauter, Guido

AU - Simon, Ronald

PY - 2008

Y1 - 2008

N2 - Oestrogen receptor alpha (ER) plays a critical, diverse and not fully understood role in endometrial carcinoma. Most endometrial carcinomas express ER and some of these tumours respond favourably to anti-oestrogen therapy. On the other hand, tamoxifen therapy constitutes a major risk factor for endometrial carcinoma development. Amplification of the ESR1 gene encoding ER was recently shown to constitute a mechanism for ER over-expression in breast carcinoma. This study was designed to determine the potential role of ESR1 amplifications in endometrial carcinoma. Tissue microarrays of 368 endometrial carcinomas and large sections of 43 cases of endometrial hyperplasia were analysed for ESR1 gene amplification and ER protein expression by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. FISH revealed ESR1 amplification in 40/176 (23%) cancers, 6/19 (32%) atypical complex hyperplasias, 3/10 (30%) complex hyperplasias without atypia and 2/14 (14%) simple hyperplasias without atypia. Strong ER protein expression was significantly linked to ESR1 amplification in endometrial carcinoma (p = 0.0036). These data indicate that ESR1 amplification might be one mechanism for ER over-expression in endometrial carcinoma, and suggest an early role for ESR1 amplification in the development of a significant fraction of endometrial carcinoma. Given the predictive role of ESR1 amplification for tamoxifen response in breast carcinoma, it will be interesting to investigate the response of ESR1-amplified endometrial cancers to anti-oestrogenic drugs.

AB - Oestrogen receptor alpha (ER) plays a critical, diverse and not fully understood role in endometrial carcinoma. Most endometrial carcinomas express ER and some of these tumours respond favourably to anti-oestrogen therapy. On the other hand, tamoxifen therapy constitutes a major risk factor for endometrial carcinoma development. Amplification of the ESR1 gene encoding ER was recently shown to constitute a mechanism for ER over-expression in breast carcinoma. This study was designed to determine the potential role of ESR1 amplifications in endometrial carcinoma. Tissue microarrays of 368 endometrial carcinomas and large sections of 43 cases of endometrial hyperplasia were analysed for ESR1 gene amplification and ER protein expression by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. FISH revealed ESR1 amplification in 40/176 (23%) cancers, 6/19 (32%) atypical complex hyperplasias, 3/10 (30%) complex hyperplasias without atypia and 2/14 (14%) simple hyperplasias without atypia. Strong ER protein expression was significantly linked to ESR1 amplification in endometrial carcinoma (p = 0.0036). These data indicate that ESR1 amplification might be one mechanism for ER over-expression in endometrial carcinoma, and suggest an early role for ESR1 amplification in the development of a significant fraction of endometrial carcinoma. Given the predictive role of ESR1 amplification for tamoxifen response in breast carcinoma, it will be interesting to investigate the response of ESR1-amplified endometrial cancers to anti-oestrogenic drugs.

M3 - SCORING: Zeitschriftenaufsatz

VL - 216

SP - 151

EP - 157

JO - J PATHOL

JF - J PATHOL

SN - 0022-3417

IS - 2

M1 - 2

ER -