Endocrine pancreatic
tumors are neuroendocrine
neoplasms with malignant potential and give rise to varied clinical syndromes due to excessive secretion of multiple
hormones. In this study 22 endocrine pancreatic
tumors and 11
carcinoid tumors were examined for the expression of CD44 using a
monoclonal antibody. CD44 gene activity of 11 endocrine pancreatic
tumor tissues and five
carcinoid tumor tissues was also studied by amplifying
messenger RNA with the polymerase chain reaction followed by electrophoresis and blot hybridization. Strong immunoreactivity was detected on all
gastrinomas examined (P < 0.001), and in two
non-functioning endocrine pancreatic tumors. Such immunoreactivity was not observed in other subtypes of endocrine pancreatic
tumors. In the normal human pancreas, the acinar portion and ductal epithelial cells stained strongly positive but pancreatic islet cells did not show any significant immunostaining. Furthermore, in endocrine pancreatic
tumors with metastatic disease, CD44-positive
tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative
tumors which were locally invasive or metastasized to the liver. Although, in this limited material and short follow-up, we were not able to show any statistical significance, patients with CD44-negative endocrine pancreatic
tumors had prolonged survival time compared with patients with CD44-positive
tumors (73% versus 59% at 5 years; P = 0.7). Of 10
carcinoid tumors examined, all three foregut
carcinoids and one midgut
carcinoid stained strongly positive, whereas all other midgut
carcinoids were negative. Analysis of CD44 splice variants showed that in all five
gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic
tumors and
carcinoid tumors. The band pattern from one case of
carcinoid tumor with a fulminant
clinical course was similar to that of
gastrinomas, whereas other
carcinoid tumors expressed the epithelial form of CD44. The earlier identified splice variants which confer metastatic behavior on a pancreatic tumor cell line were not expressed in
neuroendocrine tumors. Our data indicate that CD44 expression in endocrine pancreatic
tumors correlates with the ability to give rise to
lymph node metastases and may play a vital role in determining the fate of metastasizing cells. Moreover, because
gastrin is not detectable in the normal human pancreas, the pancreatic ductal cell positivity for CD44 strengthened the ductal origin concept of
gastrinomas. The band pattern of CD44 splice variants suggests that the previously described splice variants conferring metastatic behavior do not accompany metastatic activity of
neuroendocrine tumors.