This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McMillan, P. J. Articles by Roos, B. A. Search for Related Content PubMed PubMed Citation Articles by McMillan, P. J. Articles by Roos, B. A.

Immunohistology, Light Microscopy, and Ultrastructural Morphology of Transplantable Rat Medullary Thyroid Carcinomas¹

Department of Anatomy, Loma Linda University, Loma Linda, California 92350 [P. J. M., L. G. T., W. M. H.], and Endocrinology and Mineral Metabolism, Veterans Administration Medical Center and School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 [B. A. R.]

We recently reported growth and calcitonin (CT) parameters determined during serial transplantation of rat medullary thyroid carcinoma (MTC). After 6 to 8 tumor transplant generations, most MTC series tended to maintain characteristic rates of growth and CT production. We have selected three stable MTC series which together represent a wide range of growth and CT production for immunohistological, light microscopic, and ultrastructural analyses. These analyses have been interpreted in light of previously reported biological and immunochemical characteristics of these tumors. The fastest growing MTC series (designated 1-1-2) has the lowest CT content. The two other MTC series, 1-2-4 and 2-2-10, have somewhat slower growth and 10- to 20-fold higher CT content.

Descriptive light microscopic analyses of the tumors distinguished the 1-1-2 series by the presence of active necrosis and scar tissue and by generalized low-intensity immunoperoxidase staining (CT antibodies). Descriptive ultrstructural analyses revealed high concentrations of secretory granules in each of the 3 MTC series. However, differences in morphology and distribution of secretory granules and other cell organelles related to processing and elaboration of secretory products were noted. The highest CT-producers (MTC Series 2-2-10) had, in addition to mature secretory granules, a number of less mature, more electron-dense, prosecretory-type granules near the Golgi apparatus. Secretory granules in the 2-2-10 series tumor cells were distributed more peripherally than in the 1-2-4 series. Compared to the 2-2-10 series, the 1-2-4 series exhibited a similar number of coated and prosecretory-type vesicles in the Golgi region. The uniform staining and distribution of mature secretory granules and dilated rough endoplasmic reticulum with few attached ribosomes characterized the 1-2-4 series. The low-CT, fast-growing 1-1-2 tumors exhibited decreased mitochondria, increased lysosomes, and increased microfilaments. They also had features of cells actively elaborating secretory products such as peripheral secretory granules with varying density and prominent dilated Golgi profiles. The prosecretory-type granules, however, occupied a similar volume in this series as in 1-2-4 and 2-2-10. These results suggest that the type of secretory products and their rate of synthesis may differ among the MTC tumors, making these tumors an excellent model system for studying tumor growth and function.

¹ This work was supported by American Cancer Society Grant BC282 to Case Western Reserve University, in part by NIH Grant RR00276 to Loma Linda University, and by the Veterans Administration.

² To whom requests for reprints should be addressed.

Received 6/11/79. Accepted 1/29/80.