title: A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors.
abstract: Although most pituitary tumors are benign, some are invasive or aggressive. In the absence of specific markers of malignancy, only tumors with metastases are considered malignant. To identify markers of invasion and aggressiveness, we focused on prolactin (PRL) tumors in the human and rat. Using radiology and histological methods, we classified 25 human PRL tumors into three groups (non-invasive, invasive, and aggressive-invasive) and compared them with a model of transplantable rat PRL tumors with benign and malignant lineages. Combining histological(mitoses and labeling for Ki-67, P53, pituitary transforming tumor gene (PTTG), and polysialic acid neural cell adhesion molecule) and transcriptomic (microarrays and q-RTPCR) methods with clinical data (post-surgical outcome with case-control statistical analysis), we found nine genes implicated in invasion (ADAMTS6, CRMP1, and DCAMKL3) proliferation (PTTG, ASK, CCNB1, AURKB, and CENPE), or pituitary differentiation (PITX1) showing differential expression in the three groups of tumors (P = 0.015 to 0.0001). A case-control analysis, comparing patients in remission (9 controls) and patients with persistent or recurrent tumors (14 cases) revealed that eight out of the nine genes were differentially up- or downregulated (P = 0.05 to 0.002), with only PTTG showing no correlation with clinical course (P = 0.258). These combined histological and transcriptomic analyses improve the pathological diagnosis of PRL tumors, indicating a reliable procedure for predicting tumor aggressiveness and recurrence potential. The similar gene profiles found between non-invasive human and benign rat tumors, as well as between aggressive-invasive human and malignant rat tumors provide new insights into malignancy in human pituitary tumors.
authors.affiliation: INSERM, U842, Lyon F-69372 France.
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.forename: Carole
authors.initials: C
authors.lastname: Auger
authors.forename: Pauline
authors.initials: P
authors.lastname: Devauchelle
authors.forename: Arlette
authors.initials: A
authors.lastname: Reynaud
authors.forename: Pascale
authors.initials: P
authors.lastname: Chevallier
authors.forename: Michel
authors.initials: M
authors.lastname: Jan
authors.forename: Gilles
authors.initials: G
authors.lastname: Perrin
authors.forename: Michelle
authors.initials: M
authors.lastname: Fèvre-Montange
authors.forename: Catherine
authors.initials: C
authors.lastname: Rey
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Gérald
authors.initials: G
authors.lastname: Raverot
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Belin
authors.forename: Joël
authors.initials: J
authors.lastname: Lachuer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000302:isolation & purification*; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010911:Pituitary Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D015175:Prolactinoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014408:Biomarkers, Tumor