High expression of growth factors and growth factors receptors in ovarian metastases from ileal carcinoids. An immunoistochemical study of 2 cases.

OBJECTIVE AND DESIGN: Ovarian metastatic carcinoids are rare neoplasms that show prominent fibrosis of tumor stroma and are often associated with peritoneal carcinomatosis. We studied formalin-fixed and paraffin-embedded tumor specimens of 2 cases of ovarian metastases from ileal enterochromaffin cell carcinoids immunohistochemically to evaluate whether acidic fibroblast growth factor (aFGF), transforming growth factor-alpha (TGFalpha), and their respective receptors (fibroblast growth factor receptor-4 [FGFR4] and epidermal growth factor receptor [EGFR]) may play a role in the pathogenesis of stromal fibroblast reaction and in the mechanism of tumor dissemination. RESULTS: In both cases, the majority of tumor cells expressed immunoreactivity for aFGF, FGFR4, and TGFalpha. Immunoreactivity for FGFR4 was detected in stromal cells of both cases, while EGFR-positive stromal cells were found in only 1 case. Immunoreactivity for FGFR4 was also found in peritoneal mesothelial cells. CONCLUSIONS: The coexpression of aFGF and FGFR4 in neoplastic enterochromaffin cells suggests that aFGF may act as an autocrine factor stimulating tumor cell growth. In addition, aFGF and TGFalpha may stimulate, in a paracrine fashion, the proliferation of FGFR4- and EGFR-immunoreactive stromal fibroblasts. Finally, interaction of aFGF-immunoreactive enterochromaffin cells with FGFR4-bearing mesothelial cells may play a role in the mechanism of serosal implant and spread of tumor cells