Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma

• Published in: Modern pathology Vol. 25; no. 11; pp. 1508 - 1515
• Main Authors: Lee, Heejeong, Choi, Hyun Joo, Kang, Chang Suk, Lee, Hee Jin, Lee, Weon Sun, Park, Chul Soo
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2012; Elsevier Limited
• Subjects: 631/208/199; 631/337/384/331; 692/699/67/1517/1931; Adenocarcinoma - enzymology; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Biomarkers; Biomarkers, Tumor - analysis; Cancer; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Chi-Square Distribution; Disease Progression; Endometrial Hyperplasia - enzymology; Endometrial Hyperplasia - genetics; Endometrial Hyperplasia - pathology; Endometrial Neoplasms - enzymology; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrium; Endometrium - enzymology; Endometrium - pathology; Female; Fixatives; Formaldehyde; Gene Expression Profiling - methods; Genes; Humans; Hyperplasia; Immunohistochemistry; Internal medicine; Laboratory Medicine; Medicine; Medicine & Public Health; MicroRNAs; MicroRNAs - analysis; Middle Aged; original-article; Paraffin Embedding; Pathology; Precancerous Conditions - enzymology; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Predictive Value of Tests; PTEN Phosphohydrolase - analysis; Real-Time Polymerase Chain Reaction; Reproducibility; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Tissue Fixation; PTEN; endometrial hyperplasia and carcinoma; microRNA
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2012.111

We investigated the relationship between frequently deregulated microRNAs (miRNAs) and enodometrial pathology in an attempt to find the most dependable miRNA or combination of miRNAs to identify normal, hyperplastic and malignant endometrial tissues. We also investigated the association between those miRNAs and PTEN status. We measured the expression of six miRNAs (miR-21, 182, 183, 200a, 200c and 205) in 75 formalin-fixed, paraffin-embedded normal, hyperplastic, and malignant endometrial tissue blocks using Taqman-based real-time PCR assays. PTEN loss of expression was assessed in the same endometrial tissues by immunohistochemistry. Expression of five miRNAs (miR-182, 183, 200a, 200c and 205) was significantly higher in endometrial carcinoma (CA) when compared with complex atypical hyperplasia (CAH), simple hyperplasia (SH) and normal endometrial tissue ( P <0.05, respectively). Considering the likelihood ratio and number of parameters, the composite panel of six miRNAs was the best marker, revealing a sensitivity of 91% and a specificity of 94% in differentiating endometrial CA from endometrial hyperplasia or normal endometrium while the individual miRNAs exhibited 64–77% sensitivity and 66–91% specificity. Interestingly, in distinguishing endometrial CA from CAH, the composite panel of four miRNAs (miR-182, 183, 200a, 200c) was the best marker, producing 95% sensitivity and 91% specificity. The percentage of PTEN loss was significantly higher in endometrial CA compared with SH (68% vs 24%, P <0.05), and it was also higher in CAH compared with SH (71% vs 24%, P <005). Aberrant expression of miRNAs and loss of PTEN expression are common in endometrial hyperplasia and CA. They might serve to increase the diagnostic reproducibility and improve discrimination, especially, between CAH and CA by miRNA expression profiles and between simple and complex hyperplasia through PTEN expression patterns. Those expression profiles of biomarkers also might be used to predict the potential for progression from endometrial hyperplasia to invasive CA.