{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:16:30Z","timestamp":1792289790025,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,9,28]],"date-time":"2001-09-28T00:00:00Z","timestamp":1001635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2001,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>According to current concepts, benign proliferative breast disease (BPBD) is a direct precursor of breast cancer, in a spectrum ranging from ductal hyperplasia to overtly invasive carcinoma. In this study, comparative genomic hybridization (CGH) was used to screen ductal hyperplasia and other BPBD lesions and ductal carcinoma <jats:italic>in situ<\/jats:italic> (DCIS) for common genomic abnormalities, to test the relationship between these hyperplastic and neoplastic lesions. Immunohistochemistry for cytokeratin 5\/6 was used as a diagnostic adjunct to distinguish ductal hyperplasia from DCIS. A total of 42 cases of BPBD comprising ductal hyperplasia of the usual type (<jats:italic>n<\/jats:italic>=14), papilloma (<jats:italic>n<\/jats:italic>=22), tubular adenoma (<jats:italic>n<\/jats:italic>=3), and adenosis (<jats:italic>n<\/jats:italic>=3), as well as 52 cases of DCIS, were studied. All cases of BPBD consistently displayed the presence of a subpopulation of cytokeratin 5\/6\u2010expressing basal\u2010type cells within the proliferative lesion, whereas all of the non\u2010high\u2010grade and most of the high\u2010grade DCIS lesions lacked cytokeratin 5\/6\u2010positive cells. Whereas gross genomic alterations, as determined by CGH, were undetectable in BPBD, distinct genetic changes characterized all cases of DCIS, with one exception. These results confirm the usefulness of cytokeratin 5\/6 immunohistology in the diagnosis of BPBD and neoplastic breast lesions and support the view that BPBD and DCIS are not closely related entities and that BPBD is not an obligate direct precursor of DCIS. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.982","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T17:20:09Z","timestamp":1030296009000},"page":"415-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high\u2010molecular\u2010weight cytokeratin expression patterns"],"prefix":"10.1002","volume":"195","author":[{"given":"Werner","family":"Boecker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Buerger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"van Diest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Peter","family":"Sinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Geradts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raihanatou","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Poremba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,9,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199902)187:3<272::AID-PATH265>3.0.CO;2-2"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<383::AID-PATH299>3.0.CO;2-H"},{"key":"e_1_2_6_4_2","first-page":"146","article-title":"Risk factors for breast cancer in women with proliferative breast disease","volume":"312","author":"Dupont WD","year":"1981","journal-title":"J Natl Cancer Inst"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.9.697"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006396103777"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199907)188:3<245::AID-PATH353>3.0.CO;2-6"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH744>3.0.CO;2-Q"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(98)90028-4"},{"key":"e_1_2_6_10_2","first-page":"129","article-title":"Detection of allelic imbalance indicates that a proportion of mammary hyperplasia of usual type are clonal, neoplastic proliferations","volume":"74","author":"Lakhani SR","year":"1996","journal-title":"Lab Invest"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2000.00882.x"},{"issue":"3","key":"e_1_2_6_12_2","first-page":"41","article-title":"Benign proliferative lesions and in situ carcinoma of the breast: new immunohistological findings and their biological implications","volume":"2","author":"Bocker W","year":"1993","journal-title":"Eur J Cancer Prev"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199909000-00007"},{"key":"e_1_2_6_14_2","volume-title":"Systemic Pathology, The Breast","author":"Elston CW","year":"1998"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<396::AID-PATH286>3.0.CO;2-L"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.53.3.118"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960601)77:11<2267::AID-CNCR13>3.0.CO;2-V"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2156"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199912)189:4<521::AID-PATH472>3.0.CO;2-B"},{"key":"e_1_2_6_20_2","first-page":"202","article-title":"A critical appraisal of existing classification systems of epithelial hyperplasias and in situ neoplasia of the breast with proposals for future methods of categorization: where are we going?","volume":"16","author":"Ellis IO","year":"1999","journal-title":"Semin Diagn Pathol"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01660979"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.52.5.243"},{"key":"e_1_2_6_23_2","first-page":"1465","article-title":"Genetic changes in intraductal breast cancer detected by comparative genomic hybridization","volume":"150","author":"Kuukasjarvi T","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1200923"},{"key":"e_1_2_6_25_2","first-page":"5260","article-title":"Genetic progression, histological grade, and allelic loss in ductal carcinoma in situ of the breast","volume":"56","author":"Fujii H","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_6_26_2","first-page":"2947","article-title":"Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast","volume":"53","author":"Radford DM","year":"1993","journal-title":"Cancer Res"},{"key":"e_1_2_6_27_2","first-page":"1849","article-title":"Clonal analysis of predominantly intraductal carcinoma and precancerous lesions of the breast by means of polymerase chain reaction","volume":"54","author":"Noguchi S","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902113400604"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050429"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199803)21:3<177::AID-GCC1>3.0.CO;2-X"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.583"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000515)86:4<494::AID-IJC8>3.0.CO;2-O"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(94)00261-3"},{"key":"e_1_2_6_34_2","first-page":"1056","article-title":"Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology","volume":"29","author":"Sloane JP","year":"1998","journal-title":"Hum Pathol"},{"key":"e_1_2_6_35_2","first-page":"4721","article-title":"Comparative genomic hybridization analysis of lobular carcinoma in situ and atypical lobular hyperplasia and potential roles for gains and losses of genetic material in breast neoplasia","volume":"58","author":"Lu YJ","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5295.2057"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199912)189:4<496::AID-PATH485>3.0.CO;2-D"},{"key":"e_1_2_6_38_2","first-page":"1591","article-title":"Genetically abnormal clones in histologically normal breast tissue","volume":"152","author":"Larson PS","year":"1998","journal-title":"Am J Pathol"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64543-9"},{"key":"e_1_2_6_40_2","first-page":"1925","article-title":"Loss of heterozygosity and microsatellite instability in breast hyperplasia. No obligate correlation of these genetic alterations with subsequent malignancy","volume":"150","author":"Kasami M","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.24.2096"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.53.10.778"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(200006)191:2<138::AID-PATH611>3.0.CO;2-J"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.982","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.982","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:39:51Z","timestamp":1761039591000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,28]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,11]]}},"alternative-id":["10.1002\/path.982"],"URL":"https:\/\/doi.org\/10.1002\/path.982","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9,28]]},"assertion":[{"value":"2001-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}