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Published in: World Journal of Surgical Oncology 1/2012

Open Access 01-12-2012 | Research

Novel cancerization marker, TP53, and its role in distinguishing normal tissue adjacent to cancerous tissue from normal tissue adjacent to benign tissue

Authors: Guo-Yan Liu, Kun-Hong Liu, Yin Li, Chao Pan, Ji-Qin Su, Hong-Feng Liao, Ren-Xiang Yv, Zhao-Hui Li, Li Yuan, Huan-Jing Zhang, Chi-Meng Tzeng, Bing Xiong

Published in: World Journal of Surgical Oncology | Issue 1/2012

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Abstract

Background

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.

Methods

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).

Results

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).

Conclusions

The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation.
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Literature
1.
go back to reference Braakhuis BJ, Leemans CR, Brakenhoff RH: Using tissue adjacent to carcinoma as a normal control: an obvious but questionable practice. J Pathol. 2004, 203: 620-621. 10.1002/path.1549.CrossRefPubMed Braakhuis BJ, Leemans CR, Brakenhoff RH: Using tissue adjacent to carcinoma as a normal control: an obvious but questionable practice. J Pathol. 2004, 203: 620-621. 10.1002/path.1549.CrossRefPubMed
2.
go back to reference 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 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
3.
go back to reference Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953, 6: 963-968. 10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q.CrossRefPubMed Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953, 6: 963-968. 10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q.CrossRefPubMed
4.
go back to reference 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 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
5.
go back to reference Barreto SG, Shukla PJ: Pancreatobiliary malignancies–an appreciation of the "field cancerization theory". Arch Pathol Lab Med. 2009, 133: 850-PubMed Barreto SG, Shukla PJ: Pancreatobiliary malignancies–an appreciation of the "field cancerization theory". Arch Pathol Lab Med. 2009, 133: 850-PubMed
6.
go back to reference Gazdar AF, Minna JD: Multifocal lung cancers–clonality vs field cancerization and does it matter?. J Natl Cancer Inst. 2009, 101: 541-543. 10.1093/jnci/djp059.PubMedCentralCrossRefPubMed Gazdar AF, Minna JD: Multifocal lung cancers–clonality vs field cancerization and does it matter?. J Natl Cancer Inst. 2009, 101: 541-543. 10.1093/jnci/djp059.PubMedCentralCrossRefPubMed
7.
go back to reference Heaphy CM, Griffith JK, Bisoffi M: Mammary field cancerization: molecular evidence and clinical importance. Breast Cancer Res Treat. 2009, 118: 229-239. 10.1007/s10549-009-0504-0.CrossRefPubMed Heaphy CM, Griffith JK, Bisoffi M: Mammary field cancerization: molecular evidence and clinical importance. Breast Cancer Res Treat. 2009, 118: 229-239. 10.1007/s10549-009-0504-0.CrossRefPubMed
8.
go back to reference 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 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
10.
go back to reference Schafer M, Werner S: Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol. 2008, 9: 628-638. 10.1038/nrm2455.CrossRefPubMed Schafer M, Werner S: Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol. 2008, 9: 628-638. 10.1038/nrm2455.CrossRefPubMed
11.
go back to reference 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 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
12.
go back to reference Guarino M, Rubino B, Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007, 39: 305-318. 10.1080/00313020701329914.CrossRefPubMed Guarino M, Rubino B, Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007, 39: 305-318. 10.1080/00313020701329914.CrossRefPubMed
13.
go back to reference Chandran UR, Dhir R, Ma C, Michalopoulos G, Becich M, Gilbertson J: Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors. BMC Cancer. 2005, 5: 45-10.1186/1471-2407-5-45.PubMedCentralCrossRefPubMed Chandran UR, Dhir R, Ma C, Michalopoulos G, Becich M, Gilbertson J: Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors. BMC Cancer. 2005, 5: 45-10.1186/1471-2407-5-45.PubMedCentralCrossRefPubMed
14.
go back to reference Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M: Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009, 457: 102-106. 10.1038/nature07623.PubMedCentralCrossRefPubMed Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M: Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009, 457: 102-106. 10.1038/nature07623.PubMedCentralCrossRefPubMed
16.
go back to reference 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 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
17.
go back to reference Witz IP: Tumor-microenvironment interactions: dangerous liaisons. Adv Cancer Res. 2008, 100: 203-229.CrossRefPubMed Witz IP: Tumor-microenvironment interactions: dangerous liaisons. Adv Cancer Res. 2008, 100: 203-229.CrossRefPubMed
18.
go back to reference Witz IP: Yin-yang activities and vicious cycles in the tumor microenvironment. Cancer Res. 2008, 68: 9-13. 10.1158/0008-5472.CAN-07-2917.CrossRefPubMed Witz IP: Yin-yang activities and vicious cycles in the tumor microenvironment. Cancer Res. 2008, 68: 9-13. 10.1158/0008-5472.CAN-07-2917.CrossRefPubMed
19.
go back to reference Weinberg RA: Coevolution in the tumor microenvironment. Nat Genet. 2008, 40: 494-495. 10.1038/ng0508-494.CrossRefPubMed Weinberg RA: Coevolution in the tumor microenvironment. Nat Genet. 2008, 40: 494-495. 10.1038/ng0508-494.CrossRefPubMed
20.
go back to reference Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR: A census of human cancer genes. Nat Rev Cancer. 2004, 4: 177-183. 10.1038/nrc1299.PubMedCentralCrossRefPubMed Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR: A census of human cancer genes. Nat Rev Cancer. 2004, 4: 177-183. 10.1038/nrc1299.PubMedCentralCrossRefPubMed
23.
go back to reference Hollstein M, Sidransky D, Vogelstein B, Harris CC: p53 mutations in human cancers. Science. 1991, 253: 49-53. 10.1126/science.1905840.CrossRefPubMed Hollstein M, Sidransky D, Vogelstein B, Harris CC: p53 mutations in human cancers. Science. 1991, 253: 49-53. 10.1126/science.1905840.CrossRefPubMed
25.
go back to reference Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T: Restoration of p53 function leads to tumour regression in vivo. Nature. 2007, 445: 661-665. 10.1038/nature05541.CrossRefPubMed Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T: Restoration of p53 function leads to tumour regression in vivo. Nature. 2007, 445: 661-665. 10.1038/nature05541.CrossRefPubMed
26.
go back to reference Takahashi S, Moriya T, Ishida T, Shibata H, Sasano H, Ohuchi N, Ishioka C: Prediction of breast cancer prognosis by gene expression profile of TP53 status. Cancer Sci. 2008, 99: 324-332. 10.1111/j.1349-7006.2007.00691.x.CrossRefPubMed Takahashi S, Moriya T, Ishida T, Shibata H, Sasano H, Ohuchi N, Ishioka C: Prediction of breast cancer prognosis by gene expression profile of TP53 status. Cancer Sci. 2008, 99: 324-332. 10.1111/j.1349-7006.2007.00691.x.CrossRefPubMed
27.
go back to reference 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 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
28.
go back to reference Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W, Vogelstein B: Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature. 1992, 355: 846-847. 10.1038/355846a0.CrossRefPubMed Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W, Vogelstein B: Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature. 1992, 355: 846-847. 10.1038/355846a0.CrossRefPubMed
29.
go back to reference Kubo Y, Urano Y, Yoshimoto K, Iwahana H, Fukuhara K, Arase S, Itakura M: p53 gene mutations in human skin cancers and precancerous lesions: comparison with immunohistochemical analysis. J Invest Dermatol. 1994, 102: 440-444. 10.1111/1523-1747.ep12373002.CrossRefPubMed Kubo Y, Urano Y, Yoshimoto K, Iwahana H, Fukuhara K, Arase S, Itakura M: p53 gene mutations in human skin cancers and precancerous lesions: comparison with immunohistochemical analysis. J Invest Dermatol. 1994, 102: 440-444. 10.1111/1523-1747.ep12373002.CrossRefPubMed
30.
go back to reference Aguilar F, Harris CC, Sun T, Hollstein M, Cerutti P: Geographic variation of p53 mutational profile in nonmalignant human liver. Science. 1994, 264: 1317-1319. 10.1126/science.8191284.CrossRefPubMed Aguilar F, Harris CC, Sun T, Hollstein M, Cerutti P: Geographic variation of p53 mutational profile in nonmalignant human liver. Science. 1994, 264: 1317-1319. 10.1126/science.8191284.CrossRefPubMed
Metadata
Title
Novel cancerization marker, TP53, and its role in distinguishing normal tissue adjacent to cancerous tissue from normal tissue adjacent to benign tissue
Authors
Guo-Yan Liu
Kun-Hong Liu
Yin Li
Chao Pan
Ji-Qin Su
Hong-Feng Liao
Ren-Xiang Yv
Zhao-Hui Li
Li Yuan
Huan-Jing Zhang
Chi-Meng Tzeng
Bing Xiong
Publication date
01-12-2012
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2012
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-10-252

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