Abstract
The present study was aimed to induce skin tumours in rats by chemical carcinogen 7,12-dimethybenz(a)anthracene (DMBA), to ascertain the different stages of tumorigenesis with molecular markers and application of these markers in diagnosis of neoplasms. DMBA solution (5 pmol in 0.25 ml acetone per dose) was applied fortnightly on the skin of 35 rats in one group (Group A) for a maximum of 20 doses. In another group of 35 rats (Group B), DMBA was applied initially for three consecutive weeks as initiator followed by weekly croton oil (1% w/v in acetone) applications as promoter for 60 weeks. Control groups (10 rats each) were also taken for both the treatment groups. Skin tumours were induced in only DMBA treated rats after latent period of 22 weeks, comprising of papillomas (47%), squamous cell carcinomas (43%) and fibrosarcomas (13%). Adnexal tumours consisted only two cases, one each of sebaceous basal cell carcinoma and sweat gland adenocarcinoma. Tumours arose as soft sessile/pedunculated, multicentric growths which became large cauliflower like and multiple confluencing lesions to become bigger masses. Histopatho- logically, sequential alterations seen were epidermal hyperplasia, severe epidermal hyperplasia, papilloma, papillary carcinoma, squamous cell carcinoma and its metastasis in lungs. The indices for proliferation markers (mitoses, AgNORs and PCNA) were significantly higher for squamous cell carcinoma (9.14, 15.44 and 181.63) and papillary carcinoma (3.09, 6.40 and 79.13) compared to mild epidermal hyperplasia (1.03, 4.17 and 0.53). Immunohistochemically, 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 for invasion and metastasis. c-Myc oncoprotein was demonstrated in nucleus and cytoplasm of cancer cells by immuno-electron microscopy. In conclusion, different stages of tumour development and progression was ascertained by using molecular markers: early detection of p53 and c-Myc for cell initiation and transformation; PCNA for cell proliferative activity; p53, c-Myc and PCNA overexpression in many cells for pre-malignant lesions; excessively increased p53, c-Myc and PCNA with additional expression of hTERT and abnormal cadherin and fibronectin for invasiveness, and additional loss of cadherin and fibronectin for metastasis. Mitotic index, AgNOR counts and PCNA index were independent cell proliferation markers, each being equally capable of ranking neoplastic lesions as benign and/or malignant tumours. Overall, PCNA index had high sensitivity and reliability for differentiating borderline tumours (papillary carcinomas) from benign (papilloma). Further studies are needed to elucidate the functional differences of excessively expressed, stabilized normal p53 protein and/or mutant p53 protein vis-a-vis their ultimate impact in the oncogenesis. Role of cytoplasmic accumulation of c-Myc in malignant tumours, particularly in malignant differentiated cells with the possibility of exploitation of this property of c-Myc oncoprotein for diagnosis of cancers needs further investigation.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
