A new tissue model has been developed to study the progression from normal to metastatic adenocarcinoma of the endometrium. The interstitial matrix around the stromal cells of the proliferative phase of the normal menstrual cycle was unreactive with antibodies to laminin. However, commencing with the secretory phase, stromal cells accumulated distinct cytoplasmic- and pericellular immunoreactive material. The maximal amount of stromal cell associated laminin was observed in predecidual cells of the late secretory phase. Thus, laminin immunostaining discriminates stromal cells of the proliferative phase (being """"""""negative"""""""") from those in the secretory phase (being """"""""positive""""""""). Sixty-six cases of endometrial hyperplasia and adenocarcinomas were also stained with antibodies to laminin. Sixty-nine percent of biopsies of cystic hyperplasia and thirty percent of adenomatous hyperplasia contained laminin positive stromal cells. In contrast, stromal cells in the atypical adenomatous hyperplasia and adenocarcinomas did not react with antibody to laminin. The expression of laminin receptor in the stromal cells codistributed with laminin. Adenocarcinoma cells exhibited markedly enhanced quantities of laminin receptor compared to normal endometrial glands which contained polarized basal laminin receptors. Basement membranes of the surface epithelium, the glandular epithelium and of the vessels stained strongly with antibodies to laminin. In pre- and neoplastic tissues, laminin immunostaining revealed discontinuous and defective basement membranes. In poorly differentiated carcinomas only sparse amounts of laminin positive basement membranes were observed; these tumors in contrast exhibited cytoplasmic laminin and also significant immunoreaction with antibodies to laminin receptor. Taken together, these data point to a dynamic interrelationship between the endometrial glands and the stromal cells reflected in the extracellular matrix. This interrelationship may be disrupted during the progression to invasive adenocarcinoma.
