Molecular Pathology of Chemically-Induced &; Spontaneous Animal Tumors : Pathology of Chemically Induced Neoplasms and Evaluation of Molecular Markers in Diagnosis of Animal Tumours

DMBA-induced rat skin tumours were studied using molecular markers immunohistochemistry to elucidate different stages of chemical carcinogenesis and their evaluation in diagnosis of neoplasms in animals. Skin cancer produced through sequential histopathological changes: epidermal hyperplasia/hyperkeratinization, severe epidermal hyperplasia, papilloma, papillary carcinoma, squamous cell carcinoma/its metastasis in lungs and adnexal neoplasms. Among indices for proliferation markers (mitoses, AgNORs and PCNA), PCNA index was most reliable to differentiate benign papillomas with borderline papillary carcinomas. Immunohistochemically, the epidermal cells revealed p53, c-Myc and PCNA positive nuclear labelling for initiation and proliferation, strongly positive labelling for pre-malignant lesions and strong p53, c-Myc, PCNA and hTERT labelling for malignant transformation, and additional abnormal cadherin and fibronectin detection for invasion/metastasis. c-Myc was demonstrated in nuclei and cytoplasm of cancer cells by immuno-electron microscopy. Formalin-fixed animal and human tumour tissues showed overexpression of p53, c-Myc, PCNA and hTERT with loss of cadherin and fibronectin.