The online version of this article (doi:10.1186/1477-7819-10-252) contains supplementary material, which is available to authorized users.
Guo-Yan Liu, Kun-Hong Liu contributed equally to this work.
The authors declare that they have no competing interests.
GYL was the main initiator of this work; KHL carried out the bioinformatic analysis; YL prepared and generated TMA; CP and HFL completed the pathological diagnosis and classification; JQS, ZHL and RXY performed clinical and empirical data recoding and analysis; LY and HJZ were the principal investigators. Clinical advice and supporting, plus FFPE as tissue microarray were fully corresponding by MD, Bing Xiong. For the RNA probing design, RISH and PCR validation, Dr. Tzeng took all responsibility, plus English writing and editing. Those two people shared corresponding author as "co-coresponding". All authors read and approved the final manuscript.
The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization.
We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution).
TP53 was found to be a most reliable index (P <10-7; area under curve >87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53).
The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation.
Han B, Li S, Song D, Poisson-Paré D, Liu G, Luu-The V, Ouellet J, Li S, Labrie F, Pelletier G: Expression of 17beta-hydroxysteroid dehydrogenase type 2 and type 5 in breast cancer and adjacent non-malignant tissue: a correlation to clinicopathological parameters. J Steroid Biochem Mol Biol. 2008, 112: 194-200. 10.1016/j.jsbmb.2008.10.004. CrossRefPubMed
Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH: A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res. 2003, 63: 1727-1730. PubMed
Barreto SG, Shukla PJ: Pancreatobiliary malignancies–an appreciation of the "field cancerization theory". Arch Pathol Lab Med. 2009, 133: 850- PubMed
Leedham SJ, Graham TA, Oukrif D, McDonald SA, Rodriguez-Justo M, Harrison RF, Shepherd NA, Novelli MR, Jankowski JA, Wright NA: Clonality, founder mutations, and field cancerization in human ulcerative colitis-associated neoplasia. Gastroenterology. 2009, 136: 542-550. 10.1053/j.gastro.2008.10.086. CrossRefPubMed
Wu Y, Zhou BP: New insights of epithelial-mesenchymal transition in cancer metastasis. Acta Biochim Biophys Sin (Shanghai). 2008, 40: 643-650. 10.1111/j.1745-7270.2008.00443.x. CrossRef
Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin ML, Ordóñez GR, Bignell GR, Ye K, Alipaz J, Bauer MJ, Beare D, Butler A, Carter RJ, Chen L, Cox AJ, Edkins S, Kokko-Gonzales PI, Gormley NA, Grocock RJ, Haudenschild CD, Hims MM, James T, Jia M, Kingsbury Z, Leroy C, Marshall J, Menzies A: A comprehensive catalogue of somatic mutations from a human cancer genome. Nature. 2009, 463: 191-196. PubMedCentralCrossRefPubMed
Wang X, Wang M, MacLennan GT, Abdul-Karim FW, Eble JN, Jones TD, Olobatuyi F, Eisenberg R, Cummings OW, Zhang S, Lopez-Beltran A, Montironi R, Zheng S, Lin H, Davidson DD, Cheng L: Evidence for common clonal origin of multifocal lung cancers. J Natl Cancer Inst. 2009, 101: 560-570. 10.1093/jnci/djp054. CrossRefPubMed
- Novel cancerization marker, TP53, and its role in distinguishing normal tissue adjacent to cancerous tissue from normal tissue adjacent to benign tissue
- BioMed Central
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