Improving the Value of the Endometrial Biopsy: Molecular Diagnostics for Predicting Tumor Histotype and Stage
Bojana Djordjevic, Su-Su Xie, Russell Broaddus. University of Ottawa, Ottawa, ON, Canada; MD Anderson Cancer Center, Houston, TX
Background: Lymphadenectomy for endometrial carcinoma (EC) extends operative time and causes morbidity, so it is best reserved for patients who would benefit most from the extended surgery. By distinguishing between endometrioid and non-endometrioid carcinomas, the endometrial biopsy (EMB) guides the extent of surgical staging. This distinction can be sometimes difficult histologically, especially with carcinomas with ambiguous features. Immunohistochemistry with p53 is of limited utility, as many high grade endometrioid tumors also over-express p53. Furthermore, for endometrioid carcinomas, routine microscopic examination of an EMB does not reliably yield information on risk of nodal disease. For breast and endometrial carcinomas, higher expression of estrogen-induced genes is associated with better prognosis. The purpose of this study was to determine if quantitative assessment of such genes in EMBs could provide “value added” to the pathologic evaluation of the EMB.
Design: 128 EC cases (105 endometrioid, 23 non-endometrioid) with formalin-fixed, paraffin-embedded (FFPE) pre-operative EMBs were identified. qRT-PCR was performed to quantify the expression of EIG121, RALDH2, sFRP4, IGF-I and IGF-IR. These genes are induced by estrogen in the endometrium, and previously published genomic work performed on frozen endometrial tissues identified EIG121 to be the single best molecular fingerprint to distinguish endometrioid from non-endometrioid carcinomas. Transcripts were correlated with tumor histotype and stage in the final hysterectomy surgical specimen.
Results: EIG121 and sFRP4 were significantly increased in endometrioid carcinomas compared with non-endometrioid tumors (p<0.0001). When considering the endometrioid tumors only, RALDH2 was significantly decreased (p<0.0001) in EMBs for which the corresponding hysterectomy had positive lymph nodes. All of the endometrioid tumors with lymph node metastases were FIGO grade 2 tumors. RALDH2, sFRP4 and IGF-I were significantly elevated (p<0.0001) in early stage (I and II) endometrioid tumors compared to their advanced stage (III and IV) counterparts.
Conclusions: Analysis of estrogen-induced genes can be applied to FFPE EMBs to provide important, clinically relevant data, such as tumor histotype and stage. These assays expand the clinical value of the EMB, particularly when histological information is limited, permitting up-front identification of patients with high risk tumors who require more aggressive clinical management.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 11:00 AM
Proffered Papers: Section E, Monday Morning