IMMUNOHISTOCHEMISTRY OF CYCLIN D3 IN PULMONARY CARCINOMAS

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.