MicroRNA signatures discriminate between uterine and ovarian serous carcinomas

• Published in: Human pathology 2018-06, Vol.76, p.133-140
• Main Authors: Hui, Pei, Gysler, Stefan M., Uduman, Mohamed, Togun, Taiwo A., Prado, Daniel E., Brambs, Christine E., Nallur, Sunitha, Schwartz, Peter E., Rutherford, Thomas J., Santin, Alessandro D., Weidhaas, Joanne B., Ratner, Elena S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Cancer therapies; Carcinoma - genetics; Carcinoma - pathology; Classification; Cytokines; Deoxyribonucleic acid; Diagnosis, Differential; Differential diagnosis; DNA; DNA methylation; Endometrial cancer; Female; Gene expression; Gene Expression Profiling - methods; Genetic Predisposition to Disease; Histology; Humans; Kinases; Medical prognosis; Mesothelioma; Metastasis; MicroRNAs; MicroRNAs - genetics; Middle Aged; Neoplasm Grading; Neoplasms, Cystic, Mucinous, and Serous - genetics; Neoplasms, Cystic, Mucinous, and Serous - pathology; Oligonucleotide Array Sequence Analysis; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Ovarian serous carcinoma; Patients; Phenotype; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Studies; Synchronous serous carcinoma; Transcriptome; Tumors; Uterine Neoplasms - genetics; Uterine Neoplasms - pathology; Uterine serous carcinoma
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2018.02.019

Synchronous endometrial and ovarian malignancies occur in 5% of women presenting with endometrial cancer and 10% of patients presenting with ovarian malignancy. When a high-grade serous carcinoma concurrently involves both ovary and endometrium, pathological determination of whether they are synchronous primaries or metastatic tumors from one primary site can be challenging. MicroRNAs (miRNA) are 22-nucleotide noncoding RNAs that are aberrantly expressed in cancer cells and may inherit their cellular lineage characteristics. We explored possible differential miRNA signatures that may separate high-grade ovarian serous carcinoma from primary endometrial serous carcinoma. Forty-seven samples of histologically pure high-grade serous carcinoma of both uterine (16 case) and ovarian primaries (31 cases) were included. Expression of 384 mature miRNAs was analyzed using ABI TaqMan Low-Density Arrays technology. A random forest model was used to identify miRNAs that together could differentiate between uterine and ovarian serous carcinomas. Among 150 miRNAs detectable at various levels in the study cases, a panel of 11-miRNA signatures was identified to significantly discriminate between ovarian and uterine serous carcinoma (P < .05). A nested cross-validated convergent forest plot using 6 of the 11 miRNA signature was eventually established to classify the tumors with 91.5% accuracy. In conclusion, we have characterized a miRNA signature panel in this exploratory study that shows significant discriminatory power in separating primary ovarian high-grade serous carcinoma from its endometrial counterpart. •Expression of 384 miRNAs was analyzed in 47 cases of Müllerian serous carcinomas.•Panel of 11-miRNAs was able to separate ovarian from uterine serous carcinoma.•Random forest plot of 6 miRNAs classifies tumor primary sites with 91.5% accuracy.