Estrogen Receptor Gene Amplification Occurs Rarely in Ovarian Cancer

Rana M. Issa; Annette Lebeau; Tobias Grob; Frederik Holst; Holger Moch; Luigi Terracciano; Matthias Choschzick; Guido Sauter; Ronald Simon

Disclosures

Mod Pathol. 2009;22(2):191-196. 

In This Article

Abstract and Introduction

Abstract

Amplification of the gene encoding estrogen receptor-α occurs in about 20% of breast cancers and is an important mechanism for estrogen receptor overexpression in this tumor type. In ovarian cancer, overexpression of estrogen receptor protein has been described in more than two thirds of cases. To study a potential role of estrogen receptor-α gene amplification for estrogen receptor overexpression in ovarian cancer, a tumor tissue microarray containing 428 ovarian cancers was analyzed by fluorescence in situ hybridization for estrogen receptor-α gene amplification and immunohistochemistry for estrogen receptor expression. The estrogen receptor-α gene status was successfully determined in 243 of 428 arrayed cancers. Estrogen receptor gene amplification was found in 5 of 243 (2%) of tumors. Amplification levels were usually low, with 4-8 estrogen receptor-α gene copies. However, one case had a high-level amplification, with more than 30 estrogen receptor-α gene copies. All five amplified tumors were estrogen receptor positive, with 3 of 5 tumors showing highest (Allred score, 7-8) estrogen receptor levels. The data demonstrate that estrogen receptor-α amplification occurs only rarely in ovarian cancer.

Introduction

Worldwide, ovarian cancer is the fifth most frequent malignant tumor in women and the most common cause of death among cancers of the reproductive system.[1] Prognosis is generally poor as these cancers are often detected in late stage. The median overall survival in these patients is 24-38 months after diagnosis.[2]

Treatment options include surgical removal of the tumor mass with a maximal reduction of the peritoneal cancer mass in case of local tumor extension. In addition, topical and systemic cytotoxic therapy is applied. Ovarian cancer belongs to the group of cancers with frequent expression of steroid hormone receptors. Depending on the study estrogen receptor expression has been reported in 25-86% of ovarian cancers with the highest percentages reported in endometroid and serous subtypes.[3,4,5,6,7,8,9,10,11,12,13,14,15,16] Accordingly, endocrine therapy is a recognized option in the treatment of chemoresistant ovarian cancer after the failure of first- and second-line therapies. However, not all estrogen receptor-positive ovarian cancers respond to antiestrogen therapy, and it was suggested that it might be because of the facts that most of the studies have been retrospective, small in size without adequate selection of the patients and generally used hormonal therapy as a last-line therapy for the refractory or resistant ovarian cancers. Moreover, concerning tamoxifen, it has not been definitely clarified whether it only acts as a pure estrogen antagonist in ovarian tissue, or it has also an agonist effects.[17,18,19,20,21]

In breast cancer, we had recently described estrogen receptor-α (ESR1) gene amplification as a frequent mechanism for estrogen receptor overexpression. More than 20% of breast cancers showed ESR1 gene amplification and more than 15% additional cases low-level ESR1 gene copy number gains.[22] Preliminary data also suggested that ESR1 amplified breast cancers may exhibit a high responsiveness to tamoxifen. To determine, whether ESR1 amplifications also occur in ovarian cancer, we analyzed a set of more than 428 primary ovarian cancers for ESR1 gene amplification. The results of this study suggest that ESR1 amplification is a mechanism for estrogen receptor overexpression only in a very small subset of ovarian cancers.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....