GROWTH-PATTERN OF EXPERIMENTAL SQUAMOUS-CELL CARCINOMA IN RAT SUBMANDIBULAR GLANDS - AN IMMUNOHISTOCHEMICAL EVALUATION

Histopathological and immunohistochemical studies during carcinogenesi s in rat submandibular glands (SMGs) using a carcinogen (9,10-dimethyl -1,2-benzanthracene : DMBA) were evaluated. For carcinogenesis, the ca rcinogen-containing sponge was surgically inserted into the gland. His topathological features during carcinogenesis were as follows; dilatat ion of ductal segments, the presence of duct-like structures and cysti c lesion around the sponge were observed within 3 weeks of the experim ent, squamous metaplasia in duct-like structures and lining epithelium of the cystic structures around the sponge were observed at 4-6 weeks of the experiment, and finally well differentiated squamous cell carc inomas (SCCs) were observed after 8 weeks of the experiment. The immun oreactivity of K8.12 keration (K8.12), S-100 protein (S-100), epiderma l growth factor (EGF), laminin, and proliferating cell nuclear antigen (PCNA) were evaluated. In the normal SMG, EGF was confined to the gra nular cells and S-100 to the pillar cells of granular convoluted tubul es (GCTs). K8.12 was found in striated (SD) and excretory duct (ED) ce lls and laminin showed linear staining of the basement membrane around the ducts, acini and blood vessels. PCNA-positive nuclei were rarely observed in the normal glandular parenchyma. During carcinogenesis, du ring the first stage, EGF in granular cells and S-100 in pillar cells of GCT segments disappeared, and cytokeration K8.12 was observed in du ct-like structures and cystic epithelium around the DMBA sponge. PCNA- positive nuclei in the first stage were mainly confined to basal cells of morphologically altered ducts. During the second stage, squamous m etaplastic cells showed an intense K8.12 reaction. During the third st age, the well differentiated SCC showed strong reaction for K8.12, and the linear staining for laminin staining had disappeared at the invad ing fronts. The PCNA index was nearly 40% in the tumour cell component . The stem cells or the progenitor cells during experimental carcinoma were most likely to be the ductal basal cells, and carcinogenesis was initiated with an increase of proliferating activity in small cell cl usters surrounding a necrotic area, basal cells of dilated excretory d ucts and duct-like structures. Thus, all ductal segments undergoing sq uamous metaplasia may participate in the genesis of neoplasia during e xperimental carcinogenesis. (C) 1996 Elsevier Science Ltd