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Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma†
Version of Record online: 19 APR 2004
Published 2004 American Cancer Society
Volume 100, Issue 10, pages 2139–2147, 15 May 2004
How to Cite
Davidson, B., Alejandro, E., Flørenes, V. A., Goderstad, J.-M., Risberg, B., Kristensen, G. B., Trope, C. G. and Kohn, E. C. (2004), Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma. Cancer, 100: 2139–2147. doi: 10.1002/cncr.20219
This article is a US Government work and, as such, is in the public domain in the United States of America.
- Issue online: 29 APR 2004
- Version of Record online: 19 APR 2004
- Manuscript Revised: 24 FEB 2004
- Manuscript Accepted: 24 FEB 2004
- Manuscript Received: 12 FEB 2004
- Norwegian Cancer Society
- tumor microenvironment
The granulin-epithelin precursor (GEP) was preferentially expressed in invasive ovarian tumor epithelium specimens compared with specimens of borderline ovarian tumors. The objective of the current study was to evaluate the anatomic site-related and cellular expression of GEP and its association with clinicopathologic parameters and survival in patients with advanced-stage ovarian carcinoma.
Effusions (n = 190), corresponding primary tumor specimens (n = 64), and specimens of metastatic lesions (n = 125) were analyzed using immunohistochemistry with a specific polyclonal antipeptide antibody. In addition, 36 effusions were analyzed using immunoblotting.
GEP was detected in tumor cells in 171 of 190 (90%) effusions and demonstrated both focal membrane and cytoplasmic localization. Mesothelial cells were often GEP positive (81%). GEP was found in carcinoma cells in 180 of 189 (95%) tumor biopsy specimens, with stromal and endothelial cell expression in 93 of 180 (52%) and 124 of 185 (67%) specimens, respectively. Lower GEP expression in stromal cells was observed in metastases sampled during or after chemotherapy (P = 0.034). The presence of GEP-positive stromal cells in untreated primary tumor specimens correlated with worse overall survival (P = 0.014). Significantly more frequent GEP expression was observed in tumor cells of both primary (P = 0.002) and metastatic (P < 0.001) tissue specimens compared with malignant effusions.
GEP expression was observed in primary and metastatic epithelial ovarian carcinoma specimens, with down-regulated expression in tumor cells of malignant effusions. The poor outcome associated with stromal GEP expression suggests a prognostic role for this growth factor in ovarian carcinoma. Cancer 2004. Published 2004 American Cancer Society.