title: Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.
abstract: OBJECTIVE
  Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX).
  
  
  METHODS
  131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF.
  
  
  RESULTS
  66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p=0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome.
  
  
  CONCLUSIONS
  Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas.
authors.affiliation: Institute of Pathology, Division of Breast, Gynecologic and Perinatal Pathology, University of Leipzig, Leipzig, Germany. hornl@medizin.uni-leipzig.de
authors.forename: L-C
authors.initials: LC
authors.lastname: Horn
authors.forename: N
authors.initials: N
authors.lastname: Hommel
authors.forename: U
authors.initials: U
authors.lastname: Roschlau
authors.forename: K
authors.initials: K
authors.lastname: Bilek
authors.forename: B
authors.initials: B
authors.lastname: Hentschel
authors.forename: J
authors.initials: J
authors.lastname: Einenkel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases