title: Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system.
abstract: OBJECTIVE
  Oral squamous cell carcinoma (OSCC) is a common malignancy with a variable clinical course. One of the established survival predictors in carcinomas in general is tumour grade; in OSCC, however, grading according to the World Health Organization (WHO) has no independent prognostic impact. Recently, a novel grading scheme associated with high impact on patient outcome has been proposed for squamous cell carcinoma of the lung.
  
  
  RESULTS
  To probe whether this scheme could be applied to the upper aerodigestive tract, we retrospectively evaluated 157 chemo- and radiotherapy-naive OSCCs with complete clinical follow-up data and standardized treatment for tumour budding activity (BA), cell nest size (CNS), extent of keratinization, stromal content, nuclear size and mitotic count. Histomorphological characteristics were correlated with clinicopathological data and patient outcome. As in squamous cell carcinoma of the lung, high BA and small CNS were correlated significantly with shortened overall, disease-specific and disease-free survival. A three-tiered grading system based on a sum score of these two prognostic markers proved to be a strong age-, stage- and sex-independent prognosticator for survival with a hazard ratio for overall survival of 2.1 for intermediately differentiated (G2) tumours and 3.4 for poorly differentiated (G3) tumours compared to well-differentiated (G1) tumours (P < 0.001).
  
  
  CONCLUSIONS
  We recapitulated and validated almost exactly the strong prognostic impact of a grading algorithm proposed recently for squamous cell carcinoma of the lung in OSCC. Our data may pave the way for a prognostically highly relevant future squamous cell carcinoma grading system broadly applicable in the aerodigestive tract.
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Boxberg
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Jesinghaus
authors.affiliation: Department of Head and Neck Surgery, Klinikum Rechts der Isar, Munich, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Dorfner
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Enken
authors.initials: E
authors.lastname: Drecoll
authors.affiliation: Institute of Pathology, Heidelberg University, Heidelberg, Germany.|Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Steiger
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Bollwein
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Department of Head and Neck Surgery, Klinikum Rechts der Isar, Munich, Germany.
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Wolff
authors.affiliation: Department of Head and Neck Surgery, Klinikum Rechts der Isar, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kolk
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.|National Center of Tumor Diseases (NCT), Heidelberg, Germany.|German Cancer Consortium (DKTK), Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D060787:Neoplasm Grading / Q000379:methods*; D011379:Prognosis; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: grading; head and neck carcinoma; histomorphological characteristics; oral squamous cell carcinoma; prognosis