title: OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation.
abstract: The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19. Histopathological and immunohistochemical features were therefore compared to recipient follow-up data. Thirty-four (45%) HCCs were completely OATP-, and 18 (24%) showed positivity for K7 and/or K19. We observed a significant inverse correlation between OATP and K7/19 expression (P < 0.001): all OATP+ cases were K7/19-, while all K7+ and/or K19+ cases were OATP-. Sixteen cases were negative for all antibodies. No correlation was found between histopathological features and immunohistochemistry. Twenty-five recipients experienced HCC recurrence, and ten died from neoplastic recurrence. Neither OATP nor keratin expressions were correlated with HCC recurrence, while OATP negativity significantly correlated with HCC-related death after recurrence (P = 0.036). In conclusion, HCCs show a progressive loss in OATP immunoreactivity that correlates with the gain of a biliary phenotype. Although further studies are required to define these findings better, our results support the idea that OATP could be used together with K7/19 to identify a phenotypical "spectrum" in HCC progression.
authors.affiliation: Pathology Unit, F. Addarii Institute of Oncology and Pathology, S. Orsola-Malpighi Hospital, Viale Ercolani 4/2, 40138, Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vasuri
authors.forename: Rita
authors.initials: R
authors.lastname: Golfieri
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Elisa
authors.initials: E
authors.lastname: Capizzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Renzulli
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Pinna
authors.forename: Walter F
authors.initials: WF
authors.lastname: Grigioni
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico-Grigioni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053539:Keratin-19; D053552:Keratin-7; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000096:biosynthesis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000096:biosynthesis*; D011379:Prognosis; D012189:Retrospective Studies; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D014408:Biomarkers, Tumor; C507497:KRT7 protein, human; D053539:Keratin-19; D053552:Keratin-7; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3