Nuclear envelope organization in papillary thyroid carcinoma

Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape chang es compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expres sion of the major structural proteins of the nuclear envelope. Lamin A, lam in B1, Lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LA P2), emerin, and nuclear pores were examined. PTC's with typical nuclear fe atures by H&E were compared to non-neoplastic thyroid and follicular neopla sms using confocal microscopy, and semiquantitative immunoblotting. Lamin A /C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the gro oves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregula rities. By immunoblotting, the abundance (per cell) and electrophoretic mob ilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not dis tinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is rela ted to a loss of proliferative activity. At least three LAP2 isoforms are i dentified in normal and neoplastic thyroid. LBR is sparse or undetectable i n all the thyroid samples. The results suggest that the irregular nuclear s hape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC.