Cyclin D3, a cell cycle regulator, is encoded in the 6q21 chromosome r
egion. Abnormalities of this gene and its protein product have not bee
n found in normal tissues or in malignancies from human subjects. The
expression of cyclin D3 was studied immunohistochemically in archival
formalin-fixed, paraffin-embedded specimens from normal organs obtaine
d from three autopsy cases and 237 human primary pulmonary carcinomas.
In normal organs, nuclear positivity for cyclin D3 was observed in re
active type-2 pneumocytes, islets of Langerhans, lymphocytes from lymp
h nodes, superficial cells of transitional epithelium, epithelium of o
esophagus, stomach, small intestine and gallbladder, endothelium, smoo
th muscles, and brain. Proliferating cells such as lymphocytes in the
germinal centres and non-proliferating cells such as neurons both demo
nstrated cyclin D3 immunoreactivity. Cyclin D3 showed obvious nuclear
immunoreactivity in 168 pulmonary carcinomas (71%). The proportion of
tumour cells that were cyclin D3-positive ranged from 1% to 73% (media
n, 16%). There was no relationship between cyclin D3 immunoreactivity
and histological typing, tumour differentiation, or pathological TNM s
taging. In pulmonary carcinomas, distinct expression of the cyclin D3
protein is unlikely to be implicated in tumorigenesis, because of its
expression in only a small fraction of cancer cells. It may relate to
cancer progression. The distribution of cyclin D3 reactivity in the no
rmal tissues; suggests that cyclin D3 affects other processes than cel
l cycle regulation in a lineage-specific manner.