Connective tissue growth factor expression in endocrine tumors is associated with high stromal expression of alpha-smooth muscle actin.
OBJECTIVE
Complications due to fibrosis development are common in patients with well-differentiated endocrine carcinomas in the small intestine (ileal carcinoids). Connective tissue growth factor (CTGF) expression in ileal carcinoids may be related to this fibrosis development. This study aimed to examine CTGF expression in relation to local myofibroblast differentiation in a large series of ileal carcinoids and in different types of endocrine tumors.


METHODS
Immunoreactivity (IR) for CTGF and α-smooth muscle actin (α-SMA), a marker for myofibroblasts, was compared in serial tumor tissue sections from 42 patients with ileal carcinoids and from 80 patients with other endocrine tumors. Western blot was performed on an additional 21 patients with ileal carcinoids.


RESULTS
CTGF IR was present in >50% of tumor cells in all 42 ileal carcinoids and in 2 out of 14 endocrine pancreatic tumors, 4 out of 6 rectal carcinoids, and 1 out of 5 lung carcinoids. Tumors with abundant CTGF expression also displayed α-SMA IR in stromal fibroblast-like cells, whereas other endocrine tumors displayed less or no CTGF and α-SMA IR. Protein bands corresponding to full-length CTGF (36-42 kDa) were detected in protein lysates from ileal carcinoids.


CONCLUSIONS
CTGF is uniquely prevalent in ileal carcinoids when compared with most other endocrine tumor types. Immunoreactive cells are adjacent areas with increased fibrovascular stroma that express α-SMA. This supports a potential role for CTGF in myofibroblast-mediated fibrosis associated with ileal carcinoids, and indicates that CTGF should be investigated as a target for future therapy.
Cunningham
Janet L
JL
Section of Endocrine Oncology, Department of Medical Sciences, Lab 14, Research Department 2, Uppsala University Hospital, Uppsala University, Uppsala, Sweden. janet.cunningham@medsci.uu.se
Tsolakis
Apostolos V
AV
Jacobson
Annica
A
Janson
Eva T
ET
D000199:Actins / Q000378:metabolism*; D015153:Blotting, Western; D002276:Carcinoid Tumor / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004701:Endocrine Gland Neoplasms / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000378:metabolism*
D000199:Actins; C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor