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Article Dans Une Revue Clinical Cancer Research Année : 2014

Lung squamous cell carcinomas with basaloid histology represent a specific molecular entity

C. Brambilla
  • Fonction : Auteur
J. Laffaire
  • Fonction : Auteur
Sylvie Lantuejoul
D. Moro-Sibilot
  • Fonction : Auteur
H. Mignotte
  • Fonction : Auteur
F. Arbib
  • Fonction : Auteur
A. C. Toffart
  • Fonction : Auteur
F. Petel
  • Fonction : Auteur
S. Rousseaux
  • Fonction : Auteur
S. Khochbin
  • Fonction : Auteur
A. De Reynies
  • Fonction : Auteur
Elizabeth Brambilla
  • Fonction : Auteur

Résumé

PURPOSE: The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient. EXPERIMENTAL DESIGN: To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed). RESULTS: Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed. From this signature, we derived a 2-genes (SOX4, IVL) immunohistochemistry-based predictor that discriminated basaloid tumors (pure and mixed) from non-basaloid tumors with 94% accuracy in an independent series. The pure basaloid tumors are also distinguished through unsupervised analyses. Using a centroid-based predictor, the corresponding molecular subtype was found in 8 independent public datasets (n = 58/533), and was shown to be associated with a very poor survival as compared with other SCCs (adjusted HR = 2.45; P = 0.000001). CONCLUSION: This study enlightens the heterogeneity of SCCs that can be subclassified in mRNA expression subtypes. This study demonstrates for the first time that basaloid SCCs constitute a distinct histomolecular entity, which justifies its recognition and distinction from non-basaloid SCCs. In addition, their characteristic molecular profile highlights their intrinsic resistance to cytotoxic chemotherapy and could serve as a guide for targeted therapies.

Dates et versions

hal-01262529 , version 1 (26-01-2016)

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Citer

C. Brambilla, J. Laffaire, Sylvie Lantuejoul, D. Moro-Sibilot, H. Mignotte, et al.. Lung squamous cell carcinomas with basaloid histology represent a specific molecular entity. Clinical Cancer Research, 2014, 20 (22), pp.5777-86. ⟨10.1158/1078-0432.CCR-14-0459⟩. ⟨hal-01262529⟩

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