A limited Panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of theovary Journal Article


Authors: Köbel, M.; Kalloger, S. E.; Carrick, J.; Huntsman, D.; Asad, H.; Oliva, E.; Ewanowich, C. A.; Soslow, R. A.; Gilks, C. B.
Article Title: A limited Panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of theovary
Abstract: The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose of this study was to test and validate a set of antibodies that could aid in the diagnosis of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1β, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N=237), HNF-1β showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1, ER, and HNF-1β demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases.
Keywords: immunohistochemistry; human tissue; protein expression; major clinical study; clinical trial; histopathology; area under the curve; cancer diagnosis; diagnostic accuracy; sensitivity and specificity; adenocarcinoma; ki 67 antigen; ovarian neoplasms; diagnosis, differential; differential diagnosis; tumor markers, biological; protein p53; tumor marker; ovary; multicenter study; ovary tumor; ovary carcinoma; immunophenotyping; tissue array analysis; area under curve; tissue microarray; clear cell carcinoma; hepatocyte nuclear factor 1beta; wt1 protein; adenocarcinoma, clear cell; cystadenocarcinoma, serous; estrogen receptor; roc curve; er; hnf-1β; serous carcinoma; wt1; cyclin e; p21 activated kinase; high grade serous carcinoma; cystadenocarcinoma
Journal Title: American Journal of Surgical Pathology
Volume: 33
Issue: 1
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2009-01-01
Start Page: 14
End Page: 21
Language: English
DOI: 10.1097/PAS.0b013e3181788546
PUBMED: 18830127
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: AJSPD" - "Source: Scopus"
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  1. Haider Asad
    12 Asad
  2. Robert Soslow
    797 Soslow