Development of Novel Endometrial Cancer Molecular Diagnostics: Assessment of a qRT-PCR Biomarker Panel of Estrogen-Induced Genes Using Formalin-Fixed, Paraffin-Embedded Tissues
Russell Broaddus, Su-Su Xie, Rania Bakkar. M.D. Anderson Cancer Center, Houston, TX; University of New Mexico School of Medicine, Albuquerque, NM
Background: Two important clinical problems for endometrial cancer provide opportunity for use of novel molecular diagnostics. One, there is on-going controversy as to which endometrial cancer patients benefit from surgical staging. Intra-operative frozen section is not universally available and is unreliable in a subset of cases. Two, the pathological distinction between endometrioid and non-endometrioid carcinoma can be difficult. p53 immunohistochemistry is not always helpful in this distinction. Using frozen tissues, we previously identified genes that are induced by estrogen in the endometrium. Estrogen exposure is associated with low grade, early stage endometrioid carcinoma. We modified the qRT-PCR assays to be applied to formalin-fixed, paraffin-embedded (FFPE) tissues. We hypothesized that assessment of this gene panel could be potentially useful for these 2 clinical problems.
Design: qRT-PCR for the estrogen-induced genes EIG121, RALDH2, sFRP4, IGF-IR, and IGF-I was performed using microdissected FFPE endometrial carcinomas derived from hysterectomies (endometrioid grade 1, n=31; grade 2, n=33; grade 3, n=35; non-endometrioid, n=72). The non-endometrioid group was composed of carcinosarcoma (n=25), pure serous carcinoma (n=4), mixed endometrioid/serous carcinoma (n=31), and undifferentiated carcinoma (n=12).
Results: EIG121 and IGF-I transcripts were significantly increased in endometrioid tumors compared to non-endometrioid. EIG121, RALDH2, and sFRP4 were significantly higher in endometrioid tumors compared to mixed endometrioid-serous tumors, implying that the mixed tumors are biologically more like pure serous carcinoma. EIG121, RALDH2, and IGF-I were significantly greater in non-myoinvasive endometrial carcinomas compared to all other stages. EIG121 and RALDH2 were significantly higher in early stage disease (Stages I and II) compared to tumors with spread outside the uterus (Stages III and IV).
Conclusions: All genes in the panel could be quantified using FFPE tissues. The panel of EIG121, IGF-I, RALDH2, and sFRP4 showed the most promise in distinguishing endometrioid from non-endometrioid histologies and early stage from late stage disease. The ultimate goal is to perform these same quantitative assays in FFPE endometrial biopsies. This will potentially allow pathologists to predict tumor stage from a routinely acquired endometrial biopsy.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 204, Wednesday Afternoon