Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma.
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.
Davidson
Ben
B
Molecular Signaling Section, Laboratory of Pathology, Center for Cancer Research, The National Cancer Institute, Bethesda, Maryland 20892, USA. davidsob@mail.nih.gov
Alejandro
Emilyn
E
Flørenes
Vivi Ann
VA
Goderstad
Jeanne-Mette
JM
Risberg
Björn
B
Kristensen
Gunnar B
GB
Trope
Claes G
CG
Kohn
Elise C
EC
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000556:secondary; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000556:secondary; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D000077153:Progranulins; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins