title: Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth.
abstract: BACKGROUND
  Claudins are tight junction proteins expressed in epithelial tissues that play important roles in cell polarity and adhesion. Altered distribution of claudin-1(CLDN1) affects cell mobility and tumor invasiveness. Craniopharyngiomas (CPs) represent epithelial tumors of the sellar region, consisting of adamantinomatous (adaCP) and papillary (papCP) variants. Their tendency to infiltrate surrounding brain structures complicates successful surgery. Reliable markers are required to predict tumor behavior and to establish individualized treatment protocols.
  
  
  METHODS
  We describe the distribution pattern of CLDN1 in a large cohort of 66 adaCPs, 21 papCPs, and 24 Rathke`s cleft cyst (RCC) cases using immunohistochemistry. CLDN1 mRNA levels were analyzed with qRT-PCR in 33 CP samples. The impact on the migration potential was studied in primary adaCP cell cultures (n = 11) treated with small interfering RNA (siRNA) for CLDN1. Furthermore, CLDN1 distribution patterns and expression levels were compared between invasive (n = 16) and noninvasive (n = 17) tumor groups.
  
  
  RESULTS
  PapCPs and RCCs exhibited a distinct homogenous and membranous expression pattern, whereas CLDN1 immunoreactivity appeared weaker and more heterogeneous in adaCPs. In the latter cases, whirl-like cell clusters showed complete absence of CLDN1. mRNA analysis confirmed reduced CLDN1 levels in adaCPs versus papCPs. Interestingly, invasive tumors exhibited significantly lower CLDN1 expression compared with noninvasive counterparts regardless of CP subtype. Accordingly, siRNA treatment for CLDN1 altered tumor cell migration in vitro.
  
  
  CONCLUSIONS
  CLDN1 represents a novel marker in the differential diagnosis of CP variants and RCCs. Low CLDN1 expression levels correlate with an invasive CP growth pattern and may serve as a prognostic marker.
authors.affiliation: Corresponding author: Rolf Buslei, MD, University Hospital Erlangen, Department of Neuropathology, Schwabachanlage 6, 91054 Erlangen, Germany. rolf.buslei@uk-erlangen.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Stache
authors.forename: Annett
authors.initials: A
authors.lastname: Hölsken
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fahlbusch
authors.forename: Jörg
authors.initials: J
authors.lastname: Flitsch
authors.forename: Sven-Martin
authors.initials: SM
authors.lastname: Schlaffer
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Rolf
authors.initials: R
authors.lastname: Buslei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D062445:Claudin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D003397:Craniopharyngioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: claudin-1; craniopharyngioma; invasion; migration; tight junction