title: Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.
abstract: As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas.
authors.affiliation: Pituitary Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., B-131, Los Angeles, CA, 90048, USA, coopero@cshs.org.
authors.forename: Odelia
authors.initials: O
authors.lastname: Cooper
authors.forename: Adam
authors.initials: A
authors.lastname: Mamelak
authors.forename: Serguei
authors.initials: S
authors.lastname: Bannykh
authors.forename: John
authors.initials: J
authors.lastname: Carmichael
authors.forename: Vivien
authors.initials: V
authors.lastname: Bonert
authors.forename: Stephen
authors.initials: S
authors.lastname: Lim
authors.forename: Galen
authors.initials: G
authors.lastname: Cook-Wiens
authors.forename: Anat
authors.initials: A
authors.lastname: Ben-Shlomo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases