Moreover, the non-adenocarcinoma (SCLC) component might arise from the adenocarcinoma (NSCLC) component through a mechanism that involves the activation of the ASCL1 and PI3K/AKT1 signaling pathways.
The activated pathway in lung ADC and SCC mainly focuses on MAPK and PI3K with different key genes of each, respectively, and the activated pathway of SCLC mainly focuses on JAK-STAT pathway.
GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (P = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; P = 0.043).
When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA.
In highly differentiated adenocarcinomas the ErbB2/ErbB3 complex is activated, which is followed by phosphatidylinositol 3-kinase (PI3K) activation. p38 MAP kinase is activated downstream of PI3K and adherens junctions are disrupted via Rac1 activation.
In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3K and MEK inhibitors.
Immunohistochemical analysis was performed on colorectal adenocarcinomas and adjacent normal mucosa for PI3K pathway components, including p85alpha, p110alpha, Akt1, Akt2, and the tumor suppressor PTEN, which inhibits PI3K.
Actually, among the surgically resected lung tumors, the adenocarcinomas with the K-ras gene mutation tended to show a higher frequency and intensity of immunoreactivity for phosphorylated Akt (p-ser473Akt) than those without the mutation, supporting the in vitro observation that the mutated K-ras can activate the PI3K-Akt pathway.
Activity of the downstream PI3K effector protein kinase B (PKB) was higher in SqCas than in AdCas and was correlated with PIK3CA copy number (r = 0.75), suggesting that these copy number increases contribute to activation of PI3K signaling in SqCas of the lung.