Author of

• 10497

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  P1.01 - Poster Session 1 - Cancer Biology (ID 143)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10501

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    P1.01-004 - Role of the extracellular matrix in variations of invasive pathways in lung cancers (ID 102)

    10:12 - 10:26  |  Author(s): A. Alarcão
    • Abstract

    Background
    Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas(SqCC), is the massive degradation of the extracellular matrix (ECM); and the remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan sinthases (HAS), E-cadherin adhesion molecules, and the transformer growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation.

    Methods
    We examined HAases proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and nonsmokers.Fifty-six patients, mean age 64 years, who underwent lobectomy for AD (n = 31) and SqCC (n = 25) were included in the study.

    Results
    HAS1, 2 and 3, and Hyal 1 and 3 were significantly more expressed by tumor cells than normal and stroma cells (P<0.01) . E-cadherin and TGF-β immunostaining indices were significantly increased in the tumour cells compared to stroma cells (p<0.01). When stratified according to histologic types, HAS3 and Hyal 1 immunoreactivity was significantly increased in tumour cells of AD (p = 0.01) and stroma of SqCC (p = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS 3 immunoreactivity in tumour cells (p<0.01). Stroma cells of SqCC from non smokers patients presented a significant association with HAS3 (p<0.01). A positive association was found between TGF-β in tumor cells and HAS2 in stroma cells (R = 0.40, p= 0.03), Hyal 3 and HAS1 in stroma cells (R = 0.58 p = 0.02), Hyal 1 in tumor cells and HAS1 in stroma cells (R: 0.44, p = 0.01), Hyal 3 and HAS1 in tumor cells (R: 0.35, p = 0.01). A negative association was found between TGF-β and HAS3 (R = -0.54, p = 0.004), and TGF- β and Hyal 1 (R = -0.40, p = 0.03). A Cox model analysis show low risk of death associated with female patients (R=0.11) age < 69 yrs (R=0.02), I and II stage (R=0.18 and 0.00, respectively), and high risk of death associated to HAS2 < 14.6% (R=8.69) and HAS3 > 7.4%..

    Conclusion
    HAase,HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. An inverse relationship between epithelial and stroma biomarker expression provides a different spectrum of aggressiveness. While an overexpression of HAS1 and HAS3 indicates aggressive subtypes of SqCC and AD, an overexpression of TGF-β and E-cadherin, indicates a protective role of the ECM in avoiding invasion by tumor cells in both histological types. HAasesin resected AD and SqCC were strongly related to the prognosis,Therefore, our findings suggest that strategies aimed at preventing high HAS3 and Hyal1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis. Proof of this idea will require further study in a randomized, prospective clinical trial.