Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

Figure 4 Rat BDEneu cell transplantation model of intrahepatic cholangiocarcinoma progression. A: Gross pathology of a bisected invasive hepatic tumor (T) formed in the liver of an isogenic Fischer 344 rat at 3 wk after bile duct inoculation of 4 x 10⁶ tumorigenic rat BDEneu cholangiocytes overexpressing mutationally-activated Neu, together with associated peritoneal metastases (arrows); B: Expt 1. mean tumor size ± SD (as a % of total liver weight) of hepatic tumors that formed at a 100% incidence in isogenic rat livers at 3 wk after bile duct inoculation of 4 x 10⁶ BDEneu cells (BDEneu-BD), compared with no tumors formed in rats comparably inoculated with control non-tumorigenic BDEneo cells (BDEneo-BD) transfected to stably express the neomycin resistance gene only, in the absence of oncogenic neu n = 6; C: Expt 2. Differences in mean wet weight ± SD of hepatic tumors (relative to that of corresponding non-tumorous liver) formed at 3 wk after bile duct inoculation of 4 x 10⁶ BDEneu cells (BDEneu-BD) versus the mean wet weight of hepatic tumors that formed over the same time period following inoculation of the BDEneu cells directly into liver (BDEneu-L). ^bP≤ 0.001 (BDEneu-BD tumor versus BDEneu-L tumor). n = 4; D: Representative low power photomicrograph demonstrating neoplastic cholangiocytes within a rapidly growing BDEneu-BD intrahepatic cholangiocarcinoma to be strongly immunoreactive for plasma membrane Neu; E: Photomicrograph showing malignant cholangiocytes within a BDEneu-BD intrahepatic cholangiocarcinoma to exhibit strong uniformly positive immunoreactivity for activated Neu phosphorylated at tyrosine 1248; F: Photomicrograph of a BDEneu-BD tumor demonstrating positive cytoplasmic immunostaining for COX-2 in the cholangiocytes of the neoplastic ducts. Positive immunostaining in D-F is indicated by brown reaction product. (See References 68 and 69 for a more complete description of rat BDEneu model). (D × 66, E, F × 132).