In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 18, No. 3_Supplement ( 2012-02-01), p. A10-A10
Abstract:
Introduction: The 2004 WHO Pathological classification distinguishes two cytological subtypes of bronchioloalveolar carcinoma (BAC): mucinous (M) and non-mucinous (NM). This distinction appears to be relevant in terms of clinical characteristics, prognostic and treatment effectiveness. We attempted to better characterize the molecular profile of M relative to NM. Experimental procedures: Bronchoalveolar lavage fluid (BALF) supernatants from M-BACs (n = 23) and NM-BACs (n = 11) were analyzed for 30 cytokines (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF, PDGF, HGF, VEGF, Eotaxin, G-CSF, GM-CSF, IFNγ, CXCL-1, CXCL-8, CXCL-10, MCP-1, MIP-1α, MIP-1β, TNF-α, RANTES, VCAM-1) by Bio-Plex multiplex bead-based assay (BIORAD, Marne la Coquette, France). Cytokines of interest expression was studied on paraffin embedded specimens from surgical specimens (n = 45) using immunochemistry. EGFR and K-ras mutation analysis using direct PCR and Alk overexpression detection using immunochemistry were also performed. Univariate and multivariate analysis by Cox model was undertaken to identify the variables associated with a risk for shortened survival. Summary of results: Among the 30 chemokines analyzed, CXCL10 was the only one for which concentration was significantly higher in BALF supernatants from M-BAC (n = 23) compared to NM-BAC (n = 11) and control (n = 4) (p = 0.041). The cellular source of CXCL10 was not yet identified while CXCR3, its receptor, was expressed by tumor cells. CXCR3 was more frequently and more intensively expressed in M-BAC (n = 21) than in NM-BAC (n = 24) (52% vs 17%, p=0.023 and 52±16 vs 12±6, p = 0.047, respectively). EGFR mutation was never found in M-BAC (0%, 0/21) while present in 21% (5/24) of NM-BAC (p = 0.026). K-ras mutation and Alk overexpression did not differ between the two subtypes (2/21 vs 1/24, p & gt; 0,05 and 3/21 vs 2/24, p & gt; 0,05, respectively). The expression of CXCR3 was not associated with EGFR or K-ras mutation or Alk overexpression. In univariate analysis, factors associated with shorter survival were CXCL10 BALF concentration (HR=2.615, 95% CI: 1.102–6.206), PS & gt; 0 (HR=1.308, 95% CI: 1.131–1.726) and bilateral extension (HR=2.914, 95% CI: 1.208–7.031). Multivariate analysis did not show any independent prognostic factor. Conclusions: Our results show a CXCL10/CXCR3 overexpression in M-BAC compared to NM-BAC and suggest an association between CXCL10 overexpression and shorter survival.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.12AACRIASLC-A10
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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