Calreticulin expression is reduced in high-grade ovarian serous carcinoma effusions compared with primary tumors and solid metastases.
The objective of this study was to analyze the expression and clinical role of calreticulin, a multifunctional Ca(2+)-binding chaperone of the endoplasmic reticulum, in advanced-stage high-grade serous ovarian carcinoma. Cellular calreticulin messenger RNA (mRNA) and protein expression was investigated in 102 and 56 tumors, respectively, using reverse transcriptase polymerase chain reaction and Western blotting. Secreted calreticulin level was further analyzed in 31 effusion supernatants. Results were analyzed for association with anatomical site and clinicopathologic parameters, including survival. Calreticulin mRNA and protein were detected in 101 of 102 and 55 of 56 tumors, respectively. Calreticulin mRNA was overexpressed in solid metastases (n = 15) compared with effusions (n = 55) and primary carcinomas (n = 32; P = .009), whereas protein expression was significantly higher in solid metastases and primary carcinomas compared with effusion specimens (P = .007). Secreted calreticulin levels were higher in peritoneal compared with pleural effusions (P = .02). Higher cellular calreticulin protein expression in effusions was associated with better response to chemotherapy at diagnosis (P = .037). Calreticulin mRNA and protein expression was unrelated to patient survival. In conclusion, calreticulin is frequently expressed in serous ovarian carcinoma cells at all anatomical sites, but expression is reduced in effusions. Calreticulin protein levels in effusions may be predictive of chemotherapy response at diagnosis.
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Olga
O
Vaksman
Ben
B
Davidson
Claes
C
Tropé
Reuven
R
Reich
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010996:Pleural Effusion / Q000378:metabolism* / Q000473:pathology
D037282:Calreticulin
Calreticulin; Chemotherapy; Ovarian cancer; Survival; Tumor progression