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Prognostic Markers in Patients with Typical Bronchial Carcinoid Tumors¹

Departments of Medicine (D.G., K.Ö., B.S.) and Pathology (E.W.), University Hospital, S-751 85 Uppsala, Sweden

Address all correspondence and requests for reprints to: Dr. Dan Granberg, Department of Endocrine Oncology, Division of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden. E-mail: dan.granberg{at}medicin.uu.se

Typical bronchial carcinoids are usually considered fairly benign tumors. Metastases do however occur, and up to 10% of the patients ultimately die from their disease. To identify prognostic markers, we immunostained 43 typical bronchial carcinoids with antibodies against 8 possibly relevant hormones, oncogenes, tumor suppressor genes, adhesion molecules, and proliferation markers. Altogether 12 patients (28%) had metastatic disease, of whom 10 had regional lymph node metastases at diagnosis. Distant metastases have occurred in 5 patients (12%); all of these have died from their disease. Patients with high expression of Ki-67 had shorter survival time (P < 0.01). None of the immunostained hormones correlated to distant metastases or shorter survival time, but gastrin-releasing peptide correlated to metastatic disease (P < 0.05). All patients who died had CD44-negative tumors (P < 0.001). Nuclear nm23 staining correlated to decreased risk for metastatic disease and distant metastases per se (P < 0.01). Bcl-2 and p53 were associated with increased risk for distant metastases (P < 0.05 and P < 0.01, respectively). We conclude that some patients with typical bronchial carcinoids die from their disease and that gastrin-releasing peptide, Bcl-2, and p53 may be of importance for the malignant transformation of the tumor. Moreover, CD44, nm23, and Ki-67 may give valuable prognostic information and help identify the patients at risk of disease-related death.

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