Summary
Introduction. Breast papillary lesions represent a heterogeneous group of tumors ranging from benign to malignant, including several intermediate forms. Malignant papillary tumors are rare and their molecular characterization is still limited. A few studies pointed to the presence of specific genetic alterations that could be relevant both for diagnostic purposes and to elucidate tumour development and progression. In order to look into the issue, we compared LOH relative frequencies of four microsatellite markers located on chromosome 16 in a set of morphologically different papillary breast lesions. LOH at TP53 locus was also analyzed throughout lesions. Materials and methods. Fifteen cases were analyzed. Sections including a malignant papillary lesion, a benign lesion (when available), and normal breast tissue were selected. Fifteen malignant and twelve benign areas were microdissected using the Leica laser microdissection system (AS LMD). After DNA extraction samples were tested for the following markers: TP53, D16S423, D16S310, DS163210 and D16S476, and analyzed on ABI PRISM 3100 (Applied Biosystems, Foster city CA). Results. Fourteen malignant lesions and twelve paired benign areas appeared to be informative for at least one of the four markers on chromosome 16. In particular, LOH at loci 16p13 and 16q21 was detected in both benign and malignant lesions, whereas LOH at locus 16q23 was limited to malignant lesions. Nine malignant and seven benign lesions were informative for LOH at TP53 locus, that was found to be significantly associated (p=0.01) with the malignant phenotype. Conclusions. Our data suggest an involvement of chromosome 16 mutations in the early steps of breast papillary tumorigenesis. TP53 deletion and possibly LOH at 16q23 appear to play a role as progression factors, being they significantly associated with malignant transformation of breast papilloma.
Similar content being viewed by others
References
F Tavassoli (Eds) (1992) Papillary lesions, in Pathology of the breast. Appleton & Lange Norwalk, CT 193–228
MA Caligo L Polidoro C Ghimenti D Campani D Cecchetti G Bevilacqua (1998) ArticleTitleA region on the long arm of chromosome 16 is frequently deleted in metastatic node-negative breast cancer Int J Oncol 13 177–182
DM Radford KL Fair NJ Phillips JH Ritter T Steinbrueck MS Holt H Donis-Keller (1995) ArticleTitleAllelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q Cancer Res 55 3399–3405
CB Vos NT ter Haar C Rosenberg JL Peterse AM Cleton-Jansen CJ Cornelisse MJ Vijver Particlevan de (1999) ArticleTitleGenetic alterations on chromosome 16 and 17 are important features of ductal carcinoma in situ of the breast and are associated with histologic type Br J Cancer 81 1410–1418 Occurrence Handle10.1038/sj.bjc.6693372
S Skirnisdottir G Eiriksdottir T Baldursson RB Barkardottir V Egilsson S Ingvarrson (1995) ArticleTitleHigh frequency of allelic imbalance at chromosome region 16q22-23 in human breast cancer: correlation with high PgR and low S phase Int J Cancer 64 112–116
A Lindblom S Rotstein L Skoog M Nordenskjold C Larsson (1993) ArticleTitleDeletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases Cancer Res 53 3707–3711
DF Callen J Crawford C Derwas AM Cleton-Jansen CJ Cornelisse E Baker (2002) ArticleTitleDefining regions of loss of heterozygosity of 16q in breast cancer cell lines Cancer Genet Cytogenet 133 76–82
SR Lakhani N Collins MR Stratton JP Sloane (1995) ArticleTitleAtypical ductal hyperplasia of the breast: clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p J Clin Pathol 48 611–615
F Dorion-Bonnet S Mautalen I Hostein M Longy (1995) ArticleTitleAllelic imbalance study of 16q in human primary breast carcinomas using microsatellite markers Genes Chromosomes Cancer 14 171–181
AM Cleton-Jansen DF Callen R Seshadri S Goldup B McCallum J Crawford JA Powell C Settasatian H van Beerendonk EW Moerland VT Smit WH Harris R Millis NV Morgan D Barnes CG Mathew CJ Cornelisse (2001) ArticleTitleLoss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions Cancer Res 61 1171–1177
K Driouch F Dorion-Bonnet M Briffod MH Champeme M Longy R Lidereau (1997) ArticleTitleLoss of heterozygosity on chromosome arm 16q in breast cancer metastases Genes Chromosomes Cancer 19 185–191
H Tsuda Y Uei T Fukutomi S Hirohashi (1994) ArticleTitleDifferent incidence of loss of heterozygosity on chromosome 16q between intraductal papilloma and intracystic papillary carcinoma of the breast Jpn J Cancer Res 85 992–996
H Tsuda (1995) ArticleTitleDifferential diagnosis of intracistic papillary tumors of the breast by examination of loss of heterozygosis on chomosome 16q JPN J cancer Chemother 22 52–58
H Tsuda T Fukutomi S Hirohashi (1995) ArticleTitlePattern of gene alterations in intraductal breast neoplasms associated with histological type and grade Clin Cancer Res 1 261–267
RA Lininger WS Park YG Man T Pham G MacGrogan Z Zhuang FA Tavassoli (1998) ArticleTitleLOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast Hum Pathol 29 1113–1118
JE Eyfjord S Thorlacius M Steinarsdottir R Valgardsdottir HM Ogmundsdottir K Anamthawat-Jonsson (1995) ArticleTitlep53 abnormalities and genomic instability in primary human breast carcinomas Cancer Res 55 646–651
G Eiriksdottir RB Barkardottir BA Agnarsson G Johannesdottir K Olafsdottir V Egilsson S Ingvarsson (1998) ArticleTitleHigh incidence of loss of heterozygosity at chromosome 17p13 in breast tumors from BRCA2 mutation carriers Oncogene 16 21–26
DS Liscia R Morizio T Venesio C Palenzona M Donadio R Callahan (1999) ArticleTitlePrognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene Br J Cancer 80 821–826
JH Kang SJ Kim DY Noh IA Park KJ Choe OJ Yoo HS Kang (2001) ArticleTitleMethylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma Lab Invest 81 573–579 Occurrence Handle1:CAS:528:DC%2BD3MXjsFSisbY%3D Occurrence Handle11304577
JH Kang SJ Kim DY Noh KJ Choe ES Lee HS Kang (2001) ArticleTitleThe timing and characterization of p53 mutations in progression from atypical ductal hyperplasia to invasive lesions in the breast cancer J Mol Med 79 648–655
MA Nagai H Schaer Barbosa MA Zago W Araujo Silva SuffixJr IN Nishimoto S Salaorni LN Guerreiro Costa M Silva Araujo AG Caldas Oliveira M Mourao Neto MM Brentani (2003) ArticleTitleTP53 mutations in primary breast carcinomas from white and African-Brazilian patients Int J Oncol 23 189–196
FP O’Malley CL Vnencak-Jones WD Dupont F Parl S Manning DL Page (1994) ArticleTitlep53 mutations are confined to the comedo type ductal carcinoma in situ of the breast Immunohistochemical and sequencing data. Lab Invest, 71 67–72
V Launonen A Mannermaa F Stenback VM Kosma U Puistola P Huusko M Anttila R Bloigu S Saarikoski A Kauppila R Winqvist (2000) ArticleTitleLoss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables Cancer Genet Cytogenet 122 49–54 Occurrence Handle10.1016/S0165-4608(00)00279-X Occurrence Handle1:CAS:528:DC%2BD3cXot12ktbc%3D Occurrence Handle11104033
Z Zhuang P Bertheau MR Emmert-Buck LA Liotta J Gnarra WM Linehan IA Lubensky (1995) ArticleTitleA microdissection technique for archival DNA analysis of specific cell populations in lesions 1 mm in size Am J Pathol 146 620–625
AM Cleton-Jansen EW Moerland NJ Kuipers-Dijkshoorn DF Callen GR Sutherland B Hansen P Devilee CJ Cornelisse (1994) ArticleTitleAt least two different regions are involved in allelic imbalance on chromosome arm 16q in breast cancer Genes Chromosomes Cancer 9 101–107
Y Kitamura K Shimizu S Tanaka K Ito M Emi (2000) ArticleTitleAssociation of allelic loss on 1q, 4p, 7q, 9p, 9q, and 16q with postoperative death in papillary thyroid carcinoma Clin Cancer Res 6 1819–1825
RP Henke A Erbersdobler (2002) ArticleTitleNumerical chromosomal aberrations in papillary renal cortical tumors: relationship with histopathologic features Virchows Arch 440 604–609
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cristofano, C.D., Mrad, K., Zavaglia, K. et al. Papillary lesions of the breast: a molecular progression?. Breast Cancer Res Treat 90, 71–76 (2005). https://doi.org/10.1007/s10549-004-3003-3
Issue Date:
DOI: https://doi.org/10.1007/s10549-004-3003-3