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Hum Pathol. 2015 Oct;46(10):1427-36. doi: 10.1016/j.humpath.2015.06.009. Epub 2015 Jun 23.

Are clear cell carcinomas of the ovary and endometrium phenotypically identical? A proteomic analysis.

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Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
Vanderbilt-Ingram Cancer Center, Nashville, TN 37232.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Department of Pathology, Emory University Hospital, Atlanta, GA 30322.
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
University of Utah School of Medicine and ARUP Laboratories, Salt Lake City, UT 84112.
Department of Pathology and Laboratory Medicine, North Shore-LIJ Health System and Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY 11030.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06610, and Bridgeport Hospital, Bridgeport, CT 06606.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205.
Department of Pathology, University of Arizona College of Medicine, Tucson, AZ 85724.
Department of Pathology, University of California San Diego, San Diego, CA 92103. Electronic address:


Phenotypic differences between otherwise similar tumors arising from different gynecologic locations may be highly significant in understanding the underlying driver molecular events at each site and may potentially offer insights into differential responses to treatment. In this study, the authors sought to identify and quantify phenotypic differences between ovarian clear cell carcinoma (OCCC) and endometrial clear cell carcinoma (ECCC) using a proteomic approach. Tissue microarrays were constructed from tumor samples of 108 patients (54 ECCCs and 54 OCCCs). Formalin-fixed samples on microarray slides were analyzed by matrix-assisted laser desorption/ionization mass spectrometry, and 730 spectral peaks were generated from the combined data set. A linear mixed-effect model with random intercept was used to generate 93 (12.7%) peaks that were significantly different between OCCCs and ECCCs at the fold cutoffs of 1.5 and 0.667 and an adjusted P value cutoff of 1.0 × 10(-10). Liquid chromatography-tandem mass spectrometry was performed on selected cores from each group, and peptides identified therefrom were compared with lists of statistically significant peaks from the aforementioned linear mixed-effects model to find matches within 0.2 Da. A total of 53 candidate proteins were thus identified as being differentially expressed in OCCCs and ECCCs, 45 (85%) of which were expressed at higher levels in ECCCs than OCCCs. These proteins were functionally diverse and did not highlight a clearly dominant cellular theme or molecular pathway. Although ECCCs and OCCCs are very similar, some phenotypic differences are demonstrable. Additional studies of these differentially expressed proteins may ultimately clarify the significance of these differences.


Clear cell carcinoma; Endometrium; MALDI IMS; Mass spectrometry; Ovary

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