RESPONSE: Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non–Small-Cell Lung Cancer

Extract

In their letter, Tsurutani and Dennis identify two possible confounding factors (scoring system used for phospho-Akt analysis and therapies given after gefitinib treatment) that they suggest could impact our results regarding Akt phosphorylation in non–small-cell lung cancer (NSCLC) in patients treated with gefitinib ( 1 ) .

When we analyzed our specimens for phospho-Akt, we observed nuclear, cytoplasmic, and membrane staining. Because of the absence of any validated scoring system, in our initial analysis we adopted the same scoring criteria for phospho-MAPK and phospho-Akt, and we considered samples that had at least a moderate stain (2+) in more than 10% of cells, regardless of staining localization, as positive. Because Akt activation results in its nuclear translocation ( 2 ), we decided to take into account only nuclear staining. Importantly, when we analyzed the data for subsets of patients categorized by staining patterns (i.e., nuclear versus extranuclear versus nuclear plus extranuclear), we did not find any statistically significant differences among the patient groups because exclusive nuclear or extranuclear localization rarely occurred. Therefore, we believe that our findings do not underestimate the number of tumors with activated Akt. Moreover, in our study, activated Akt was observed in 49.5% of patients, which is less than the 67% reported by Lee et al. ( 3 ) but is similar to the 53% reported by Mukohara et al. ( 4 ), who used a scoring system that considered specimens with moderate staining (2+) in more than 5% of cells as positive.