Prognostic value of immunohistochemistry in gastric neuroendocrine (carcinoid) tumors

Eur J Gastroenterol Hepatol. 2007 Jan;19(1):21-8. doi: 10.1097/01.meg.0000250582.30737.bd.

Abstract

Three subtypes of enterochromaffin-like cell tumors (carcinoids) have been described: type I, associated with chronic atrophic gastritis; type II, multiple endocrine neoplasia 1 and Zollinger-Ellison syndrome; and type III, sporadic tumors.

Objectives: (i) To investigate the immunoexpression of Ki-67, p53 and Bcl-2 proteins in enterochromaffin-like cell (carcinoid) tumors and (ii) to evaluate the prognostic value of these markers.

Methods: Fifty-four samples from 21 patients with gastric carcinoid tumors were sectioned and immunostained using avidin-biotin peroxidase method.

Results: The mean age was 62.2+/-11.4 years (36-83 years-old) and 13 (61.9%) were women. Type I lesions were detected in 61.9% and type III in 38.1%. Tumors were single in 10 (47.6%) and were multiple and/or multicentric in 11 (52.4%). Nuclear p53 immunoreactivity was observed in 6/21 patients (28.6%), and all of them were type III tumors (6/8), compared with no p53 expression in type I (0/13), P=0.0002. p53 expression was also associated with high degree of cell proliferation (Ki-67-positive nuclear cells), P=0.00001. Bcl-2 expression was either unreactive or weakly positive in all tumor lesions. The mean follow-up period was 50.4 months (SD=45.2), varying from 6 to 144 months. Overall survival time of patients with positive p53 expression and high proliferative rate was significantly lower than that of negative patients (14.4 vs 123 months, P=0.0007).

Conclusions: (i) p53 immunoexpression associated with high proliferative rate was useful to distinguish between type I and type III gastric carcinoid tumors and (ii) these markers were able to predict a shorter survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoid Tumor / diagnosis*
  • Carcinoid Tumor / pathology
  • Cell Proliferation
  • Female
  • Gastroscopy
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53