Virchows Archiv B Cell Pathol (1991) 60:83-89 Virchows ArchlyB CellPathology Including Molecular P ~ 9 Springer-Verlag 1991 Altered tenascin expression during spontaneous endometrial carcinogenesis in the BDII/Han rat Giinter Vollmer 1, Friedrich Deerberg z, Gene P. Siegal 3, and Rudolf Knuppen 1 t Institut f/ir Biochemische Endokrinologie, Medizinische Universit/it, Ratzeburger Allee 160, W-2400 L/ibeck, Federal Republic of Germany 2 Central Institute for Laboratory Animal Breeding, Herman-Ehlers-AIlee 57, W-3000 Hannover 91, Federal Republic of Germany 3 Department of Pathology and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill. Current address: Department of Pathology, University of Alabama at Birmingham, UAB Station, Birmingham, Alabama 35294, USA Received April 13 / Accepted December 28, 1990 Summary. The BDII/Han rat develops spontaneous en- dometrial adenocarcinoma, which appears virtually identical histologically to human endometrial adenocar- cinoma. The incidence rate of cancer formation in the rat is 90% and the mean lifetime of the animals is 22 months. This animal model therefore, is useful in the study of molecular aspects of spontaneous transforma- tion as well as mammalian neoplastic progression. In this study we address the in-situ expression of tenascin, an extracellular matrix glycoprotein, during normal cycl- ic growth, during development of proliferative states, and during malignant transformation of the endome- trium. Trace amounts of immunocytochemically detect- able tenascin were found in 10% of young BDII/Han rats with a normal estrus cycle. In these inbred animals no tenascin was detectable in uteri without neoplastic progressive alterations of the endometrium. Tenascin im- munoreactivity first appeared during proliferation in one of three uteri with cystic glandular hyperplasia. Promi- nent tenascin expression was detectable in all adenoma- tous hyperplasia, but restricted to the stromal mesen- chyme, that surrounded the glands. In all endometrial adenocarcinomas tested, essentially the entire extracellu- lar space of the stromal mesenchyme was immunoreac- tive with anti-tenascin antibodies while the epithelial glands themselves were negative. This staining pattern was observed independent of the degree of tumor differ- entiation or extent of myometrial invasion. The tenascin staining pattern was not significantly altered in tumors transplanted into the soft tissues of the neck of female BDII/Han rats. From our studies we conclude that ten- ascin may be a marker for the early detection of prolifer- ative endometrial states. Further, previous investigation by us showing nearly identical findings in human endo- metrium reinforces the value of this animal model system in the study of human epithelial hyperplastic conditions Offprint requests to: G. Vollmer including those associated with malignancies of the en- dometrium. Key words: Uterus - Endometrial adenocarcinoma - Ex- tracelluar matrix - Epithelial/mesenchymal interactions A number of laboratories have independently detected and described a novel extracellular matrix glycoprotein (for review see (Erickson and Lightner 1988) which was first characterized under the rubric myotendinous anti- gen (Chiquet and Fambrough 1984; Chiquet and Fam- brough 1984), but is now known as tenascin/hexabra- chion. Recently its DNA sequence has been ascertained (Jones et al. 1988; Gulcher et al. 1989). Tenascin is ex- pressed only in minimal amounts in adult, differentiated organs (Chiquet-Ehrismann et al. 1986) but seems to me- diate epithelial/mesenchymal interactions during normal growth and development (Aufderheide et al. 1987, Auf- derheide and Ekblom 1988; Mackie et al. 1987; Thesleff et al. 1987). Subsequent work has emphasized that the presence and time-dependent expression of tenascin is both important for the normal embryonic development of an animal and is inappropriately re-expressed during disordered proliferative states associated with tumor growth, in for example the mouse mammary gland (In- aguma et al. 1988). Furthermore, tenascin has been de- scribed as a stromal marker for epithelial malignancies of the human breast (Mackie et al. 1987). The BDII/Han rat has been used as an animal model for spontaneous hormone-dependent tumorigenesis of the endometrium (Deerberg and Kaspareit 1987). After an average lifespan of less than 2 years these animals develop endometrial adenocarcinomas which are mainly moderately differentiated. However, the differentiation pattern ranges from well to poorly differentiated and metastatic tumors are known to develop. Based on histo-