Copy Number Aberrations in Benign Serous Ovarian Tumors: A Case for Reclassification?

Abstract

Purpose: Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis.Experimental Design: High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N ¼ 39) and borderline (N ¼ 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays.Results: CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33%

Type-Specific Cell Line Models for Type-Specific Ovarian Cancer Research

“…Unfortunately, historical records of ovarian cancer cell lines have rarely included information on histological origin [32], [64]; this is further hampered by a historical lack of reproducibility in histological diagnosis [73]–[75]. Histopathological reproducibility is steadily improving as recognition of the five major histotypes as unique disease entities becomes more widespread [4], [7], [8], [15], [22], [44], [76], [77], histology and grading criteria become unified [78]–[81], and objective biomarker based tools to delineate histotypes are developed [2], [4], [41], [44]. However, cell lines lack morphological features that are recognizable in culture and development of new, well-defined, cell lines is laborious with poor long-term success rates.…”

Pre-Invasive Ovarian Mucinous Tumors Are Characterized by CDKN2A and RAS Pathway Aberrations

“…However, it was notable that the coincidence of RAS activation and homozygous CDKN2A inactivation was higher in the borderline tumors (P ¼ 0.06, Fishers exact test) with only 3 of 20 benign tumors harboring both aberrations compared with 13 of 22 borderline tumors (P ¼ 0.005, Fisher's exact test). Interestingly, in our previous study of serous benign and borderline tumors (27), deletion of CDKN2A/2B was not observed, despite a high incidence of RAS pathway activation in serous borderline tumors ($60%).…”

“…Chromosome 12 gain has been observed as a frequent CNA in the stroma of benign serous cystadenomas and cystadenofibromas, at lower rates in serous borderline ovarian tumors (27), and commonly in pure fibromas (43). HD of the CDKN2A/2B locus was observed in the adjacent epithelial DNA in all 3 cases, indicating that these tumors are molecularly very similar to the other tumors in the cohort despite the presence of co-existing stromal neoplasia.…”

“…In contrast to serous cystadenomas and cystadenofibromas in which such mutations are not observed (27)(28)(29), the rate of KRAS mutation in mucinous cystadenomas has been reported at 46% to 55% (30)(31)(32). This rate increases to 63% to 73% in borderline tumors (31,33) and 75% to 85% in mucinous carcinomas (31,33).…”

Cistoadenoma seroso ovárico gigante en la posmenopausia. Reporte de un caso

“…La mayoría de los cistoadenomas serosos son policlonales, pero ocurren cistoadenomas monoclonales; asimismo, se desarrollan como una expansión hiperplásica a partir de inclusiones epiteliales y muestran cambios en el número de copias de ADN en las células epiteliales en algunos casos 13 .…”