Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas

Abstract

Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERβ). ERα has been described as a cancer promoter and ERβ, as a possible tumor suppressor. Both receptors are present at low levels in primary multiforme glioblastoma (GBM). The GBM frequency is 50 % higher in men than in women. The GBM patient survival period ranges from 7 to 18 months. The purpose of this pilot study was to evaluate aromatase and estrogen receptor expression, as well as 17ß-estradiol concentration in astrocytoma patients biopsies to obtain a prognosis biomarker for these patients. We analyzed 36 biopsies of astrocytoma patients with a different grade (I-IV) of malignity. Aromatase and estrogen receptor mRNA expression were analyzed by semiquantitative RT-PCR, and the E2 levels, by ELISA. E2 concentration was higher in GBM, compared to grade II or III astrocytomas. The number of cells immunoreactive to aromatase and estrogen receptors decreased as the grade of tumor malignity increased. Aromatase mRNA expression was present in all biopsies, regardless of malignity grade or patient age or gender. The highest expression of aromatase mRNA in GBM patients was associated to the worst survival prognostic (6.28 months). In contrast lowest expression of ERα mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ERα expression could be used as prognosis biomarkers for astrocytoma patients.

Estrogen Receptor Expression in Glial Tumors of Iranian Patients: A Single Center Experience

“…IRANIAN JOURNAL OF PATHOLOGY ERα and ERβ bind to the different ligands and studies have shown that ERα can enhance the proliferation of cancer cells, while ERβ has a potential role as a tumor suppressor. Several studies have demonstrated that high-grade gliomas are frequently associated with loss of ERβ expression, which results in a poor clinical outcome (6,7).…”

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

“…The most recent advance in treatment is the use of temozolomide as a chemotherapeutic agent. This drug has increased the mean survival time by 2.5 months and survival after two years by approximately 16% 3 , 4 , 20 , 21 , 22 , 23 , 24 .…”

“…Achieving prognostic improvements and more effective treatment seems to depend on the understanding and manipulation of molecular and genetic pathways that regulate the aberrant growth of these tumors. In particular, biomolecular markers have introduced further information concerning this topic in recent decades 2 , 21 , 25 , 26 , 27 , 28 , 29 .…”

“…Estrogens seem to have a protective effect on the development of gliomas because they occur more commonly in men than in women. In women, the incidence of gliomas increases during the postmenopausal period, when estrogen levels are low 3 , 14 , 18 , 30 .…”

Novel Endocrine Targets for GBM Therapy

“…GBM exhibits different endocrine characteristics. GBM expresses high levels of estrogen receptor alpha (mRNA ERα) and low levels of estrogen receptor beta (ERß); expression of mRNA ERα is positively correlated to the survival of GBM patients and could be used as a prognostic factor [26]. In contrast, the low expression of ERß in GBM has been related to a worse prognosis for survival and could be used as a biomarker for prognosis too [27,28].…”