The von Hippel-Lindau Gene Product (pVHL) and Kidney Injury Molecule-1 (KIM-1) Are Useful Diagnostic Markers for Identifying Focal Clear Cell Carcinoma of the Uterus
H Liu, JW Prichard, J Shi, PL Zhang, W Dupree, F Lin. Geisinger Medical Center, Danville, PA; William Beaumont Hospital, Royal Oak, MI
Background: Identification of even a small proportion of clear cell carcinoma (CCC) in uterine adenocarcinoma is important because focal CCC is considered a high-grade carcinoma, and the patient would receive more aggressive treatment. Differentiation of CCC from clear cell features (CCF) resulting from other conditions, such as squamous differentiation, secretory change, and mucinous change, can be challenging. No absolutely sensitive and specific tumor-associated markers are available to make this distinction. Our recent study demonstrated that pVHL was a relatively sensitive (90%) and specific marker for identifying CCC of both the uterus and ovary (Lin et al; AJCP 2008;129:592). In addition, KIM-1, a sensitive and specific marker for clear cell renal cell carcinoma, also showed some utility in the diagnosis of CCC of the ovary and uterus (Lin et al; AJSP 2007;31:371-381). In this study, we further investigate the usefulness of these two markers in identifying focal CCC of the uterus.
Design: A total of 64 paraffin blocks from 20 cases of uterine adenocarcinoma with focal CCF were included. Of the 20 cases, 17 cases were endometrioid carcinoma with focal CCF; and 3 cases were papillary serous carcinoma with focal CCF. Immunohistochemical stains with antibodies against pVHL and KIM-1 were performed as previously described. The staining intensity and distribution were recorded. The H&E-stained slides with clear cell features were marked and compared to the positively stained areas by either pVHL and/or KIM-1.
Results: A membranous/cytoplasmic staining for pVHL was observed in 11 of 20 cases (28 paraffin blocks). The pVHL-positive areas matched the H&E slides with clear cell features. In contrast, KIM-1 with membranous/cytoplasmic positivity was observed in 6 of 20 cases (11 paraffin blocks). The KIM-1-positive areas also matched the H&E slides with clear cell features. All KIM-1-positive cases were also positive for pVHL.
Conclusions: These data indicate that pVHL and KIM-1 may serve as diagnostic markers for identifying and confirming focal clear cell carcinoma presented in adenocarcinoma of the uterus, which in turn may minimize the over-diagnosis of other conditions such as squamous differentiation and secretory change as focal clear cell carcinoma. Further study in a large series with clinical follow-up is warranted to confirm this finding.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 155, Wednesday Afternoon