The spectrum of neuroendocrine differentiation among gastrointestinal carcinoids - Importance of histologic grading, MIB-1, p53, and bcl-2 immunoreactivity

Context,-The advent of panneuroendocrine markers has helped to better depic t the heterogeneity of gastrointestinal carcinoids. Consequently, it has be en proposed that these tumors constitute a histologic spectrum that include s well-, moderately, and poorly differentiated carcinoids. However, the rep roducibility of this grading system and its prognostic importance have some times been called into question. Objective,-To investigate the potential utility of cell proliferation and o ncoprotein markers in augmenting the histologic classification. Design and Setting-Retrospective study; tertiary care teaching hospital. Methods,-Fifty-eight patients with 41 well-differentiated, 12 moderately di fferentiated and 5 poorly differentiated carcinoids from various topographi c sites of the gastrointestinal tract were selected and immunostained for p anneuroendocrine markers, MIB-1, p53, and bcl-2. Main Outcome Measures,-Degree of association between histologic grading, MI B-1, p53, and bcl-2 immunoreactivity and carcinoid metastatic behavior. Results,The group comprised 30 males and 28 females whose mean age. was 52. 7 years (range, 14-81), Mean follow-up time was 85.8 months. All 58 patient s tested positive for chromogranin A and/or synaptophysin. The group was di vided into nonmetastatic (42/58, or 72.4%) and metastatic (16/58, or 27.6%) eases. Histologic grading tended to be associated with metastatic spread, but this occurrence of metastases did not attain statistical significance ( P = .08). positivity for MIB-1 (P = .004) and p53 (P = .04) was significant ly associated with metastatic behavior, whereas bcl-2 was not (P = 0.63). Conclusions,Although an organoid pattern and neuroendocrine immunophenotype help to define the spectrum of gastrotestinal carcinoids, this study sugge sts that the histologic grading of these tumors has some limitations with r espect to predicting metastatic behavior. However, MIB-1 and p53 can compli ment histologic grading as prognostic indicators in this regard while bcl-2 appears to be less useful.