Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3

Abstract

Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer. The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively. Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases). Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67), CD34 and CA15-3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3) and in the epithelium/epithelial glands (MIB-1) of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers, taken together, could be adopted as a panel of prognostic factors in the evaluation of the gallbladder carcinoma.

Improved Outcomes in Gallbladder Cancer with Early Diagnosis and Negative Nodal Status

“…Most clinical studies only sporadically determine tumor markers in GBC, likely due to the lack of suspicion for the disease. Recent studies in tumor markers that show that CA15-3 expression can assist in discriminating between GBC and chronic cholelithiasis, but tumor markers in this study were limited to CEA, CA19-9, CA125, and AFP [25]. Elevated CA19-9 level has been described as an independent variable predictive of poor survival in GBC [27].…”

“…Tumor markers are important in the preoperative workup of various gastrointestinal cancers. In GBC, tumor markers are related to the transformation and proliferation of neoplastic cells, but have yet to show prognostic value or survival benefit [25,26]. Most clinical studies only sporadically determine tumor markers in GBC, likely due to the lack of suspicion for the disease.…”

Gallbladder cancer stem cell markers: An updated brief review

“…CD34 expression is considered as a useful indicator/marker in the differential diagnosis of gallbladder clinical features, discriminating patients with primitive gall bladder carcinoma from those with cholelithiasis [42].…”

Adenocarcinoma of the Gallbladder: Biology of Disease, Prognosticators, and Staging

“…Forced expression of LAPTM4B in a CG cell line increased the invasive potential (Zhou et al 2007. CG expresses neurotrophin, nerve growth factor, and the receptor TrkA (Artico et al 2010), but the biologic significance of this expression has not yet been elucidated. Glucose uptake is generally augmented in cancer cells.…”