The Spectrum of Neuroendocrine Differentiation Among Gastrointestinal Carcinoids

Abstract

Abstract Context.—The advent of panneuroendocrine markers has helped to better depict the heterogeneity of gastrointestinal carcinoids. Consequently, it has been proposed that these tumors constitute a histologic spectrum that includes well-, moderately, and poorly differentiated carcinoids. However, the reproducibility of this grading system and its prognostic importance have sometimes been called into question. Objective.—To investigate the potential utility of cell proliferation and oncoprotein 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 differentiated and 5 poorly differentiated carcinoids from various topographic sites of the gastrointestinal tract were selected and immunostained for panneuroendocrine markers, MIB-1, p53, and bcl-2. Main Outcome Measures.—Degree of association between histologic grading, MIB-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 patients tested positive for chromogranin A and/or synaptophysin. The group was divided into nonmetastatic (42/58, or 72.4%) and metastatic (16/58, or 27.6%) cases. 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 significantly 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 suggests that the histologic grading of these tumors has some limitations with respect to predicting metastatic behavior. However, MIB-1 and p53 can compliment histologic grading as prognostic indicators in this regard while bcl-2 appears to be less useful.