The objective of this study was to investigate spontaneous
islet cell carcinomas with particular reference to possible existing strain differences between Sprague Dawley (SD) and Wistar (W) rats in incidence and immunohistochemical staining pattern. Secondly the occurrence of
somatostatin and/or
gastrin-positive
islet cell tumors should be tested. Islet cell
adenocarcinomas (34 from SD, 43 from W-rats) were selected from the RITA-data base and company in-house data base out of an animal pool of 3915 (1681 SD, 2234 W-rats). They were untreated or
sham-treated (vehicle) control animals from carcinogenicity studies and whole life-span experiments.
Islet cell carcinomas occurred in a higher incidence in male rats (2.98% for SD, 3.23% for W) than in female rats (1.07% for SD, 0.63% for W). All specimens were immunohistologically stained with
antibodies against
insulin,
glucagon,
somatostatin and
gastrin and, selected specimens with additional
antibodies (
pancreatic polypeptide,
lipase,
chymotrypsin,
S100-protein, actin and
cytokeratin). 94% (SD) and 93% (W), respectively, were
insulin-positive and the mean staining intensity (on a scale ranging from 0-4) for
insulin was 3.58 (SD) versus 3.37 (W). This high
insulin staining incidence and intensity characterized most
islet cell carcinomas as malignant
insulinomas. 24% (SD) and 37% (W), respectively, were
glucagon-positive. Except two
tumors in W-rats with a focal strong
glucagon expression, the mean staining intensity for
glucagon was low (0.38 SD, 0.72 W). 38% (SD) and 44% (W), respectively, were
somatostatin-positive, but except for five cases having a focal to multifocal, moderate to marked staining, only a few
tumor cells were positive for
somatostatin in the other cases and the mean staining intensity for
somatostatin was low (0.50 SD, 0.84 W). 6% (SD) and 23% (W), respectively, were
gastrin-positive, but only one case of a male Wistar rat exhibited a focal strong staining in parts of the
tumor. The other cases showed only a few
tumor cells which were positive for
gastrin. The mean staining intensity for
gastrin was low (0.06 SD, 0.35 W). In all
tumors with marked
glucagon,
somatostatin or
gastrin expression, the immunostaining for
insulin was still predominating. Thus,
insulin was the major
hormone produced by most of the
tumor cells. Five out of 77
tumors evaluated were immunohistologically negative with all applied
antibodies.
CONCLUSION: This study presents the first immunohistochemical survey on spontaneous
islet cell carcinomas in SD and Wistar rats stained with
antibodies against the endocrine pancreas
hormones insulin,
glucagon,
somatostatin and
gastrin. No major differences in incidence or immunohistochemical staining pattern between SD and W-rats could be detected. In contrast to SD rats, Wistar rats had multihormonal coexpression in 16.3%. The multihormonal appearance of the
neoplasms is well comparable with the findings in other animal species and human
insulinomas. Moreover, this is the first study in rats which reports five cases with a marked co-expression of
somatostatin and one case with marked focal co-expression of
gastrin in malignant islet cell
adenocarcinomas.