title: Identification of Differentially Expressed miRNAs in Appendiceal Mucinous Cystadenocarcinoma from Mucinous Cystadenoma.
abstract: OBJECTIVE
  Mucinous cystadenocarcinoma of appendix is a rare entity. Differentiating mucinous cystadenocarcinoma from mucinous cystadenoma is very challenging and depends on establishing the presence of malignant cells in the appendix wall. The invasion may be very difficult to assess in some cases, especially in early stages of the disease, which could have devastating prognostic effects on patients. Therefore, it is necessary to develop an ancillary test that can differentiate the mucinous cystadenocarcinoma from mucinous cystadenoma. So far, there is no report available about the role of differentially expressed miRNAs in the diagnosis of appendiceal mucinous cystadenocarcinoma.
  
  
  METHODS
  Six confirmed mucinous appendiceal cystadenocarcinoma and twelve mucinous appendiceal cystadenoma cases were selected. The total RNAs were extracted from the formalin-fixed paraffin-embedded specimen of these cases. The comprehensive miRNA microarray expression profiling from pooled aliquots of RNA samples from these two entities were analyzed to detect the differentially expressed miRNAs in mucinous cystadenocarcinoma. The best seven differentially expressed miRNAs were validated in individual cases by quantitative reverse transcriptase PCR (qRT-PCR).
  
  
  RESULTS
  The microarray miRNA expression profiling analysis revealed 646 miRNAs that were differentially expressed in the mucinous cystadenocarcinoma. Among these differentially expressed miRNAs, the expression of 80 miRNAs showed statistical difference (p<0.01). The quantitative RT-PCR validated that the expression of miR-1,miR-4328was significantly down regulated in mucinous cystadenocarcinoma compared to the mucinous cystadenoma (p<0.05). On the other hand, the expression ofmiR-200b, miR-200c, miR-451, miR-223andmiR-21were significantly upregulated in mucinous cystadenocarcinoma (p<0.05).
  
  
  CONCLUSIONS
  The expression levels of miRNAs tested were significantly altered in the appendiceal mucinous cystadenocarcinoma samples compared to the mucinous cystadenoma. These data suggest that the miRNA expression in mucinous appendiceal neoplasm may help to supplement the morphological evaluation in distinguishing benign from malignant tumors.
authors.affiliation: Department of Pathology, Jackson Memorial Hospital, University of Miami, Miami, Florida, USA.
authors.forename: Richard Licheng
authors.initials: RL
authors.lastname: Wu
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Shadan
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA; Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Rafic
authors.initials: R
authors.lastname: Beydoun
keywords: FFPE; Mucinous cystadenocarcinoma; Mucinous cystadenoma; miRNAs; qRT-PCR