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. 1995 Apr;48(2):M74–M78. doi: 10.1136/mp.48.2.m74

Loss of heterozygosity in lobular carcinoma in situ of the breast

S R Lakhani 1,2, N Collins 1,2, J P Sloane 1,2, M R Stratton 1,2
PMCID: PMC407928  PMID: 16695985

Abstract

Aims—(1) To investigate whether loss of heterozygosity identified at various loci in invasive breast carcinoma or is present in lobular carcinoma in situ (LCIS). (2) To investigate whether LCIS is a monoclonal (neoplastic) or a polyclonal (hyperplastic) proliferation.

Methods—Forty three cases of LCIS (30 with associated invasive carcinoma or in situ ductal carcinoma (DCIS) and 13 cases of pure LCIS) were investigated for loss of heterozygosity on chromosomes 16q, 17q, 17p, and 13q using a microdissection technique, polymorphic DNA markers, and the polymerase chain reaction (PCR).

Results—Loss of heterozygosity was detected in both subgroups of LCIS at all the loci examined. There was no significant difference in the frequency of the loss between the group associated with invasive carcinoma and the pure LCIS group. The frequency of loss of heterozygosity ranged from 8% on 17p to 50% on 17q.

Conclusions—Because of the nature of the technique employed, our findings show that LCIS is a monoclonal (neoplastic) proliferation rather than a hyperplastic proliferation. The incidence of loss of heterozygosity on 17p (D17S796) is lower than we have observed previously in DCIS, suggesting that LCIS and DCIS are different genetically as well as clinically and morphologically. The similar incidence of loss of heterozygosity on 16q and 17q, however, suggests that DCIS and LCIS may share a common pathway of evolution.

Keywords: Breast cancer

Keywords: lobular carcinoma in situ

Keywords: loss of heterozygosity

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Selected References

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  1. Beute B. J., Kalisher L., Hutter R. V. Lobular carcinoma in situ of the breast: clinical, pathologic, and mammographic features. AJR Am J Roentgenol. 1991 Aug;157(2):257–265. doi: 10.2214/ajr.157.2.1853802. [DOI] [PubMed] [Google Scholar]
  2. Ciatto S., Cataliotti L., Cardona G., Bianchi S. Risk of infiltrating breast cancer subsequent to lobular carcinoma in situ. The Coordinating Center and Writing Committee of FONCAM (National Task Force for Breast Cancer). Tumori. 1992 Aug 31;78(4):244–246. doi: 10.1177/030089169207800405. [DOI] [PubMed] [Google Scholar]
  3. Claus E. B., Risch N., Thompson W. D., Carter D. Relationship between breast histopathology and family history of breast cancer. Cancer. 1993 Jan 1;71(1):147–153. doi: 10.1002/1097-0142(19930101)71:1<147::aid-cncr2820710124>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  4. Devilee P., van Vliet M., van Sloun P., Kuipers Dijkshoorn N., Hermans J., Pearson P. L., Cornelisse C. J. Allelotype of human breast carcinoma: a second major site for loss of heterozygosity is on chromosome 6q. Oncogene. 1991 Sep;6(9):1705–1711. [PubMed] [Google Scholar]
  5. Domagala W., Markiewski M., Kubiak R., Bartkowiak J., Osborn M. Immunohistochemical profile of invasive lobular carcinoma of the breast: predominantly vimentin and p53 protein negative, cathepsin D and oestrogen receptor positive. Virchows Arch A Pathol Anat Histopathol. 1993;423(6):497–502. doi: 10.1007/BF01606541. [DOI] [PubMed] [Google Scholar]
  6. Easton D. F., Bishop D. T., Ford D., Crockford G. P. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1993 Apr;52(4):678–701. [PMC free article] [PubMed] [Google Scholar]
  7. Frykberg E. R., Santiago F., Betsill W. L., Jr, O'Brien P. H. Lobular carcinoma in situ of the breast. Surg Gynecol Obstet. 1987 Mar;164(3):285–301. [PubMed] [Google Scholar]
  8. Hall J. M., Lee M. K., Newman B., Morrow J. E., Anderson L. A., Huey B., King M. C. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990 Dec 21;250(4988):1684–1689. doi: 10.1126/science.2270482. [DOI] [PubMed] [Google Scholar]
  9. Hutter R. V. The management of patients with lobular carcinoma in situ of the breast. Cancer. 1984 Feb 1;53(3 Suppl):798–802. doi: 10.1002/1097-0142(19840201)53:3+<798::aid-cncr2820531331>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  10. Lattes R. Lobular neoplasia (lobular carcinoma in situ) of the breast - a histological entity of controversial clinical significance. Pathol Res Pract. 1980;166(4):415–429. doi: 10.1016/S0344-0338(80)80242-1. [DOI] [PubMed] [Google Scholar]
  11. Moll R., Mitze M., Frixen U. H., Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol. 1993 Dec;143(6):1731–1742. [PMC free article] [PubMed] [Google Scholar]
  12. Ottesen G. L., Graversen H. P., Blichert-Toft M., Zedeler K., Andersen J. A. Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group. Am J Surg Pathol. 1993 Jan;17(1):14–21. doi: 10.1097/00000478-199301000-00002. [DOI] [PubMed] [Google Scholar]
  13. Page D. L., Dupont W. D. Anatomic markers of human premalignancy and risk of breast cancer. Cancer. 1990 Sep 15;66(6 Suppl):1326–1335. doi: 10.1002/1097-0142(19900915)66:14+<1326::aid-cncr2820661405>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  14. Page D. L., Dupont W. D., Rogers L. W., Landenberger M. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer. 1982 Feb 15;49(4):751–758. doi: 10.1002/1097-0142(19820215)49:4<751::aid-cncr2820490426>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  15. Page D. L., Kidd T. E., Jr, Dupont W. D., Simpson J. F., Rogers L. W. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol. 1991 Dec;22(12):1232–1239. doi: 10.1016/0046-8177(91)90105-x. [DOI] [PubMed] [Google Scholar]
  16. Poller D. N., Hutchings C. E., Galea M., Bell J. A., Nicholson R. A., Elston C. W., Blamey R. W., Ellis I. O. p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor. Br J Cancer. 1992 Sep;66(3):583–588. doi: 10.1038/bjc.1992.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sato T., Tanigami A., Yamakawa K., Akiyama F., Kasumi F., Sakamoto G., Nakamura Y. Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res. 1990 Nov 15;50(22):7184–7189. [PubMed] [Google Scholar]
  18. Urban J. A. Bilaterality of cancer of the breast. Biopsy of the opposite breast. Cancer. 1967 Nov;20(11):1867–1870. doi: 10.1002/1097-0142(196711)20:11<1867::aid-cncr2820201111>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  19. Weber J. L., Kwitek A. E., May P. E., Wallace M. R., Collins F. S., Ledbetter D. H. Dinucleotide repeat polymorphisms at the D17S250 and D17S261 loci. Nucleic Acids Res. 1990 Aug 11;18(15):4640–4640. [PMC free article] [PubMed] [Google Scholar]
  20. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
  21. Wooster R., Neuhausen S. L., Mangion J., Quirk Y., Ford D., Collins N., Nguyen K., Seal S., Tran T., Averill D. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994 Sep 30;265(5181):2088–2090. doi: 10.1126/science.8091231. [DOI] [PubMed] [Google Scholar]

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