Effects of Gefitinib at six months after administration of N-Nitrosomorpholine (NNM) and expression patterns of epidermal growth factor receptor (EGFR), transforming growth factor α (TGFα) and downstream signaling in pre-neoplastic foci of altered hepatocytes (FAH) and neoplastic liver lesions. Gefitinib was administered daily for three months (10 mg/kg) (A); Glycogen storing foci of altered hepatocytes (FAH) after NNM administration (NNM 6 months) with an overexpression of EGFR and TGFα, which is reduced after Gefitinib treatment for three months (NNM 6 months & 3 months), implying downregulation of proteins of dependent signaling pathways of phosphatidyl-inositide 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) (p-mTOR and phosphorylated 4E-binding protein 1 (p-4EBP1)) and rat sarcoma/rat sarcoma-activated factor/mitogen activated protein kinase/extracellular regulated kinase kinase (Ras/Raf/MEK/ERK) (Ras and PanERK) pathways, corresponding to less proliferative activity and volume fraction of FAH in Gefitinib treated rats (B). After six months of NNM administration (NNM 6 months), hepatocellular adenomas (HCA) and carcinomas (HCC) reveal a strong of TGFα, to a lesser extent of EGFR. Gefitinib treatment for two weeks or three months (NNM (6 months & 2 weeks)/(6 months & 3 months)) does not alter protein expression levels. Immunostaining scores are shown in brackets. Arrows correspond to ↑ upregulation, ↓ downregulation or ↔ unchanged expression level. Expression levels of immunostaining are given in brackets. Magnification: (A) overview 40×; marked lesion in dashed lines (PAS and immunostainings) 100×; and (B) (H & E and immunostainings) 100×; marked area in dashed lines (EGFR) 400×.