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

Abstract

Purpose: Lung cancer is the leading cause of cancer related mortality in the world. BAC is a subset of NSCLC that has recently gained attention because of distinct biologic 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: 46 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 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 vs. 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, 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.

The Expressions of pAkt and PTEN in Lung Cancer Patients 24 Hours After the Cisplatin-Based Chemotherapy: A Prospective Pilot Study

“…This result was in accordance with the study (in press) by Tsurutani et al 15 in which they found that 95% of all the lung cancer patients had Akt expression. The pAkt expression was reported to be observed both in cytoplasm and nu-cleus according to the previous reports 16,17 but we observed in nucleus only.…”

“…In fact, it was recently reported that there was not found any association with Akt and the survival. 15 In our study, we found a positive correlation between pAkt and PTEN expressions although a negative correlation was also reported. 22 In contrast to these two different findings, it was also reported that there was no correlation between Akt and PTEN.…”

Female Gender Is an Independent Prognostic Factor in Non-small-cell Lung Cancer: A Meta-analysis

“…Percentages of adenocarcinoma in individual studies ranged from 17.3% to 100%. 51,66,67) Disease stages included varied from study to study; some studies analyzed only stage IA disease undergoing complete resection, 46,53,62,65) while some others included only unresectable stage IIIB and IV patients scheduled for chemotherapy or chemoradiotherapy. 56,59,75) Final statistical analyses used either univariate or multivariate analyses, or both.…”

Jolkinolide B induces apoptosis in MDA-MB-231 cells through inhibition of the PI3K/Akt signaling pathway

“…Activated PI3K initiates the activation of the downstream kinase Akt. Moreover, phosphorylated Akt could facilitate cell survival and proliferation and regulate various signaling pathways (29)(30)(31). It has been shown that the activation of PI3K and Akt could inhibit autophagy (32).…”