Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

AP-PCR genomic fingerprinting in non small cell lung cancer: a shot gun approach hunting for prognostic markers

I Bagni MD, MD Beccati MD, M Matteuzzi DSc, I Nenci PhD

Dept Experimental and Diagnostic Medicine, Section of Morbid Anatomy, Histopathology and Citopathology, University of Ferrara, Ferrara, Italy

AIM: To identify genetic patterns related to clinical evolution in Non Small Cell Lung Cancer (NSCLC), paying attention to localized disease, by evaluating AP-PCR as an alternative to classical assays. METHODS: 73 NSCLCs, out of 193, are collected, with a mean and median follow-up of 5,4 and 5,7 years respectively, in which immunohistochemical characterization for p53, Bcl-2, Neu, EGF-r, p170, ploidy and proliferation index was previously studied for biological staging. We performed separate fluorescent AP-PCR with two different primers, AR3 and MCG1. RESULTS: More than 20 DNA fragments, ranging from 100 to 1000nt, are reproducibly amplified by AP-PCR, with each single primer. The fingerprintings evaluation underlines both quantitative (number in a single case) and qualitative alterations (hot spots, evaluated for different histotypes, Stage and outcome). The quantitative analysis confirms the genomic complexity of NSCLC making difficult any correlation between number of alterations and prognosis. The presence of hot spots, instead, frequently shared in localization by different histotypes, but different for kind of alteration (Gain versus Loss), is, in some cases, related to prognosis and/or progression, but not to immunohistochemical results. Concerning biological markers, in Stage 1 (70 patients) only p53 hyperexpression (62%) is related to a better prognosis (P=0,039). CONCLUSIONS: Define some NSCLC as more aggressive in early stage, will be an important means to attain improvements in patients management. AP-PCR seems to be an helpful method for studying this neoplasia, which doesn't show particular markers, and so needs a shot-gun approach.

KEY WORDS: p53, genomic fingerprinting, prognostic markers.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic risk assessment.