Granulin‐epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma
Open Access
- 19 April 2004
- Vol. 100 (10) , 2139-2147
- https://doi.org/10.1002/cncr.20219
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.Keywords
Funding Information
- Norwegian Cancer Society
This publication has 27 references indexed in Scilit:
- Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesisJournal of Molecular Medicine, 2003
- Effusion cytology in ovarian cancer: new molecular methods as aids to diagnosis and prognosisClinics In Laboratory Medicine, 2003
- Progranulin (acrogranin/PC cell‐derived growth factor/granulin‐epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine developmentDevelopmental Dynamics, 2003
- Cancer Statistics, 2003CA: A Cancer Journal for Clinicians, 2003
- Cellular Localization of Gene Expression for ProgranulinJournal of Histochemistry & Cytochemistry, 2000
- Modulation of Mouse Preimplantation Embryo Development by Acrogranin (Epithelin/Granulin Precursor)Developmental Biology, 2000
- Structure and chromosomal location of the human granulin geneBiochemical and Biophysical Research Communications, 1992
- Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.Proceedings of the National Academy of Sciences, 1992
- Granulins, a novel class of peptide from leukocytesBiochemical and Biophysical Research Communications, 1990
- Epithelins 1 and 2: isolation and characterization of two cysteine-rich growth-modulating proteins.Proceedings of the National Academy of Sciences, 1990