Prediction of Lymph Node Metastasis in Patients with Endometrioid Endometrial Cancer Using Expression Microarray

Abstract

Purpose: To characterize the gene expression profiles of endometrioid endometrial cancers associated with lymph node metastasis in an effort to identify genes associated with metastatic spread. Experimental Design: Tumors from 41 patients with endometrioid endometrial cancer grossly confined to the uterine cavity were evaluated. Positive lymph nodes were noted in 12 of 41 patients. RNA was analyzed for gene expression using the Affymetrix HG133A and HG133B GeneChip set, representing 45,000 array features covering >28,000 UniGene clusters. Data analysis was done using multidimensional scaling, binary comparison, and hierarchical clustering. Gene expression for several differentially expressed genes was examined using quantitative PCR. Results: Gene expression data was obtained from 30,964 genes that were detected in at least 5% of the cases. Supervised analysis of node-positive versus node-negative cases indicated that 450 genes were significantly differentially expressed between the two classes at P < 0.005, 81of which were differentially expressed by at least 2-fold at P < 0.005. Overexpressed genes included two cell cycle checkpoint genes, CDC2 and MAD2L1, which have previously been described in association with lymph node metastasis in other cancer types. The ZIC2 zinc finger gene was overexpressed in endometrial cancers with positive nodes versus those with negative nodes. Conclusion: Gene expression profiling of the primary tumors in patients with endometrioid endometrial cancers seems promising for identifying genes associated with lymph node metastasis. Future studies should address whether the status of nodal metastasis can be determined from the expression profiles of preoperative tissue specimens.Most endometrioid endometrial cancers are confined to the uterus at diagnosis, but f15% of apparent early stage cases have occult metastases and are destined to develop recurrence. Surgical staging, including selective lymphadenectomy, facilitates identification of patients who have metastatic disease. The decision to perform selective lymphadenectomy generally is made intraoperatively based on known risk factors such as histologic grade and depth of myometrial invasion. The risk of pelvic lymph node metastases is >10% in patients with cancers that are poorly differentiated or that invade the outer half of the myometrium (1). Surgical staging facilitates individualization of adjuvant therapy by identifying those at highest risk of recurrence. In addition, there is some evidence that surgical resection of nodal metastases may have a therapeutic benefit (2).Although several risk factors for nodal metastasis have been identified, they have a low positive predictive value in clinical practice. For example, less than half of patients with poorly differentiated, deeply invasive endometrial cancers have lymph node metastases. In addition, preoperative radiologic testing using ultrasound (3), computed tomography (4), or magnetic resonance imaging (5) is suboptimal in identifying patients with pelvic or paraao...

Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing

“…7A). Furthermore, enrichment of metastatic gene signatures in other cancer types (Bidus et al 2006;Rickman et al 2008) was also found in control versus hnRNPM knockdown cells (Supplemental Fig. S7).…”

Galectin-1 and Its Involvement in Hepatocellular Carcinoma Aggressiveness

“…Human mutations in ZIC family members determine many clinically significant congenital abnormalities (54). Moreover, aberrant expression of ZIC2 has been observed in medulloblastomas (55), small cell lung cancers (56), endometrial cancer with node metastasis (57) and in bladder, colon and breast cancer (56). OGFRL1 encodes the opioid growth factor receptor-like 1, whose biological function is unknown.…”

Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells

“…The expression of Caveolin-2 is positively correlated with tumour grade and squamous features of urothelial carcinoma (Fong et al, 2003) and it forms hetero-oligomeric complexes with Caveolin-1, that are correlated to disease progression and metastasis in human prostate cancer (Thompson et al, 1999). PTTG1 is a novel oncogene that may serve as a prognostic marker for tumour invasiveness and metastasis (Ramaswamy et al, 2003), and MAD2L1 has been associated with lymph node metastasis of several cancer types (Bidus et al, 2006). THBS1 was the gene most correlated with E2F3 knockdown; it has been linked to Abbreviation: MHC, major histocompatibility complex.…”