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V.K. De Sa



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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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): V.K. De Sa

      • 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.

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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-002 - Epidermal Growth Factor Receptor Mutations in Primary and Metastatic Adenocarcinomas from a Tertiary Hospital in Sao Paulo, Brazil (ID 98)

      09:30 - 09:30  |  Author(s): V.K. De Sa

      • Abstract

      Background
      Recently, the epidermal growth factor receptor (EGFR) mutation emerges promise as target for molecular therapy in Adenocarcinomas of the lung. However, a number of clinical features are associated with EGFR mutations: women, never-smokers than former or current smokers and Asians than other ethnic groups. Sao Paulo population is made up of a confluence of people of several different origins, from the original Native Americans, with the influx of Portuguese colonizers, Black African slaves, and recent European, Arab and Japanese immigration. Other significant groups include Koreans, Chinese, Paraguayans and Bolivians. The aim of this study was to evaluate the frequency and distribution of EGFR mutations in 100 consecutive patients with surgically excised primary and metastatic Adenocarcinomas.

      Methods
      Direct bidirectional sequencing evaluated EGFR gene mutations on exons 18 to 21 and was correlated with ethnia (East-Asian or European), gender, age, tobacco history, primary (N=75) or metastatic (N=25) and histologic subtypes.

      Results
      Twenty-eight tumors (28%) exhibited EGFR mutation. The most frequent EGFR mutation detected was a deletion in exon 19 (50%), followed by multiple mutations in the exon 20 (28%) and an L858R amino acid substitution in exon 21 (21,4%). EGFR mutation was significantly associated with men (N=59), older patients (>60yrs), smokers, non-East Asian or non-European origins, primary tumor and acinar predominant histologic subtype.

      Conclusion
      Our results indicate that if the current clinical features were strictly followed as the criteria for selecting patients for EGFR testing, a substantial number of patients who might benefit from treatment will be excluded.

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    P1.20 - Poster Session 1 - Early Detection and Screening (ID 172)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P1.20-009 - New potential marker for the diagnosis of lung cancer: Hyaluronan. (ID 3087)

      09:30 - 09:30  |  Author(s): V.K. De Sa

      • Abstract

      Background
      HA concentration is elevated in several cancers, but there is no data regarding its concentration in the sputum of lung cancer patients. In this study, we examined the HA concentrations in tissue and sputum samples and its impact on the screening and diagnosis of lung cancer patients.

      Methods
      Hyaluronic Acid (HA) was examined in lung cancer tissue of 14 patients through immunohistochemistry using a HA-probe. The analysis was performed using ImageProPlus 7.0. The HA concentration in sputum samples of 90 lung cancer patients, 25 COPD patients and 15 healthy controls was also analyzed. All the patients and healthy controls selected underwent a sputum induction. Sputum samples were incubated with urea 7M at 60[o]C and afterwards incubated with a proteolytic enzyme. The levels of HA were measured by a noncompetitive ELISA-like fluorometric assay.

      Results
      It was observed a different expression pattern of HA in squamous cell carcinomas vs. adenocarcinomas specimens (p<0.05). In sputum, a significant different concentration pattern of HA was found among lung cancer, COPD and healthy individuals (p<0.001; Fig1A). Equally significant was the difference between HA in the sputum from lung cancer and healthy volunteers (p<0.001), as well as lung cancer and COPD patients (p=0.002). ROC curve between lung cancer and healthy volunteers furnished an area of 0.821 (0.727–0.915). Assuming a cut off value of 31,44ng/mg, the specificity was 100% and the sensitivity was 51% (Fig1B). ROC curve to distinguish COPD patients from lung cancer patients showed an area of 0.698 (0.600-0.797) and the cut off value of 48.3ng/mg presented 100% of specificity and 33% of sensitivity (Fig1C). Figure 1

      Conclusion
      The results presented suggest a promising role of HA in the developing and progression of lung cancer and its concentration in the sputum as a novel diagnostic marker for differentiating normal from lung cancer patients.