Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma

Junji Tsurutani, Seth M. Steinberg, Marc Ballas, Matthew Robertson, Jaclyn LoPiccolo, Hiroshi Soda, Shigeru Kohno, Valgardur Egilsson, Phillip A. Dennis

Research output: Contribution to journalArticle

Abstract

Purpose: Lung cancer is the leading cause of cancer related mortality in the world. Bronchioloalveolar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Results: Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI, 1.07-4.71, p = 0.032), advanced stage (III or IV) (HR 2.17, 95% CI, 1.004-4.71, p = 0.049) and smoking status (HR 6.89, 95% CI, 1.49-31.88, p = 0.013) were associated with a worse prognosis. Conclusions: Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.

Original languageEnglish (US)
Pages (from-to)115-121
Number of pages7
JournalLung Cancer
Volume55
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

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Bronchiolo-Alveolar Adenocarcinoma
Proportional Hazards Models
Survival
Smoking
Histology
Phospho-Specific Antibodies
Iceland
Negative Staining
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Lung Neoplasms
Clinical Trials
Mortality
Antibodies
Incidence

Keywords

  • Akt
  • Bronchioloalveolar carcinoma
  • NSCLC
  • Prognostic factor
  • Smoking

ASJC Scopus subject areas

  • Oncology

Cite this

Tsurutani, J., Steinberg, S. M., Ballas, M., Robertson, M., LoPiccolo, J., Soda, H., ... Dennis, P. A. (2007). Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma. Lung Cancer, 55(1), 115-121. https://doi.org/10.1016/j.lungcan.2006.09.026

Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma. / Tsurutani, Junji; Steinberg, Seth M.; Ballas, Marc; Robertson, Matthew; LoPiccolo, Jaclyn; Soda, Hiroshi; Kohno, Shigeru; Egilsson, Valgardur; Dennis, Phillip A.

In: Lung Cancer, Vol. 55, No. 1, 01.2007, p. 115-121.

Research output: Contribution to journalArticle

Tsurutani, J, Steinberg, SM, Ballas, M, Robertson, M, LoPiccolo, J, Soda, H, Kohno, S, Egilsson, V & Dennis, PA 2007, 'Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma', Lung Cancer, vol. 55, no. 1, pp. 115-121. https://doi.org/10.1016/j.lungcan.2006.09.026
Tsurutani, Junji ; Steinberg, Seth M. ; Ballas, Marc ; Robertson, Matthew ; LoPiccolo, Jaclyn ; Soda, Hiroshi ; Kohno, Shigeru ; Egilsson, Valgardur ; Dennis, Phillip A. / Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma. In: Lung Cancer. 2007 ; Vol. 55, No. 1. pp. 115-121.
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abstract = "Purpose: Lung cancer is the leading cause of cancer related mortality in the world. Bronchioloalveolar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Results: Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63{\%} of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95{\%} CI, 1.07-4.71, p = 0.032), advanced stage (III or IV) (HR 2.17, 95{\%} CI, 1.004-4.71, p = 0.049) and smoking status (HR 6.89, 95{\%} CI, 1.49-31.88, p = 0.013) were associated with a worse prognosis. Conclusions: Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.",
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AU - Steinberg, Seth M.

AU - Ballas, Marc

AU - Robertson, Matthew

AU - LoPiccolo, Jaclyn

AU - Soda, Hiroshi

AU - Kohno, Shigeru

AU - Egilsson, Valgardur

AU - Dennis, Phillip A.

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N2 - Purpose: Lung cancer is the leading cause of cancer related mortality in the world. Bronchioloalveolar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Results: Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI, 1.07-4.71, p = 0.032), advanced stage (III or IV) (HR 2.17, 95% CI, 1.004-4.71, p = 0.049) and smoking status (HR 6.89, 95% CI, 1.49-31.88, p = 0.013) were associated with a worse prognosis. Conclusions: Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.

AB - Purpose: Lung cancer is the leading cause of cancer related mortality in the world. Bronchioloalveolar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Results: Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI, 1.07-4.71, p = 0.032), advanced stage (III or IV) (HR 2.17, 95% CI, 1.004-4.71, p = 0.049) and smoking status (HR 6.89, 95% CI, 1.49-31.88, p = 0.013) were associated with a worse prognosis. Conclusions: Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.

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