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Polysialylated-Neural Cell Adhesion Molecule Expression in Rat Pituitary Transplantable Tumors (Spontaneous Mammotropic Transplantable Tumor in Wistar-Furth Rats) Is Related to Growth Rate and Malignancy¹

Laboratoire de Biopathologie Nerveuse et Musculaire (JE 2053), Institut de Biologie du Développement de Marseille, Université de la Méditerranée, Faculté de Médecine Timone, 13385 Marseille cedex 05 [L. D., W. R., D. F-B.]; Laboratoire d’Histologie et d’Embryologie Moléculaire et Institut National de la Santé et de la Recherche Médicale U433, Faculté de Médecine Lyon RTH-Laennec, 69372 Lyon cedex 08 [J. T., P. C.]; Service de l’Information Médicale, Hôpital de la Timone, 13385 Marseille cedex 05 [J. G.]; and Laboratoire de Génétique et de Physiologie du Développement, Institut de Biologie du Développement de Marseille, 13288 Marseille cedex 09 [G. R.], France

Pituitary adenomas are usually benign neuroendocrine tumors. However, some of those that are histopathologically undistinguishable behave aggressively and metastasize. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is highly expressed during the development of the brain and pituitary, is detected in some neuroendocrine tumors and might be relevant as a prognostic marker in pituitary tumors. In the present study, we have searched for PSA-NCAM expression in four lineages of rat pituitary transplantable tumors (SMtTW). Each lineage, maintained by serial tumor grafts under the kidney capsule and skin, differed in its GH/Prl secretion, growth rate, and malignant behavior. PSA-NCAM expression, detected by immunohistochemistry and Western blotting and quantified by ELISA, varied according to the SMtTW lineage. The benign tumors, SMtTW₂, with a low growth rate never expressed PSA-NCAM. Another benign lineage, SMtTW₃, with a high growth rate expressed a low amount of PSA-NCAM. The highest PSA-NCAM expression was seen in tumors that grew beneath the skin, invaded the kidney, and metastasized (SMtTW₄). Tumors of the SMtTW₁₀ lineage, which behaved as either benign or malignant tumors, were heterogeneous in terms of PSA-NCAM expression.

In this rat transplantable pituitary tumor model, PSA-NCAM expression correlated in decreasing order with: (a) invasiveness (P < 0.0001), (b) metastases (P = 0.004), (c) ability to grow under the skin (P = 0.006), and (d) growth rate under the kidney capsule (P < 0.01), but not with hormone secretion (r = 0.207). This model, which is very similar to the human pathology, suggests that PSA-NCAM evaluation is of interest in the diagnosis of malignancy and the prognosis of human pituitary tumors. In addition, the SMtTW tumors could be instrumental in evaluating the effects of new therapeutic agents modulating PSA-NCAM expression.

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