Virchows Archiv

, Volume 461, Issue 3, pp 313–322

Keratin expression in breast cancers

  • Mu-Min Shao
  • Siu Ki Chan
  • Alex M. C. Yu
  • Christopher C. F. Lam
  • Julia Y. S. Tsang
  • Philip C. W. Lui
  • Bonita K. B. Law
  • Puay-Hoon Tan
  • Gary M. Tse
Original Article


Cytokeratin (CK) immunohistochemistry can play an important role in breast carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs in a large cohort of breast cancers and assessed its correlation with other biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was observed in more than 90 % of all breast carcinomas in this study, confirming their efficacy in immunohistochemical identification of breast cancer. A combination of CK8 and CK7 gave the highest sensitivity for detection of a minute number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and CK20, correlated positively with high tumour grade. The expression of CK5/6 and CK14 in a significant number of high-grade tumours raised concern regarding the use of absence of their expression to identify breast carcinoma. For identification of the basal subtype, CK5/6 gave a higher detection rate than CK14. CK20 expression was found more frequently than reported in previous studies, might constitute an indicator of poor prognosis and may be associated with the molecular apocrine subtype. This study highlights the diagnostic and prognostic relevance of the unique CK expression patterns in breast cancer.


Breast cancer Cytokeratin Immunohistochemistry CK20 


  1. 1.
    Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31(1):11–24PubMedCrossRefGoogle Scholar
  2. 2.
    Moll R, Zimbelmann R, Goldschmidt MD, Keith M, Laufer J, Kasper M, Koch PJ, Franke WW (1993) The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation 53(2):75–93PubMedCrossRefGoogle Scholar
  3. 3.
    Bader BL, Jahn L, Franke WW (1988) Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived therefrom, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Eur J Cell Biol 47(2):300–319PubMedGoogle Scholar
  4. 4.
    Popescu NC, Bowden PE, DiPaolo JA (1989) Two type II keratin genes are localized on human chromosome 12. Hum Genet 82(2):109–112PubMedCrossRefGoogle Scholar
  5. 5.
    Romano V, Bosco P, Rocchi M, Costa G, Leube RE, Franke WW, Romeo G (1988) Chromosomal assignments of human type I and type II cytokeratin genes to different chromosomes. Cytogenet Cell Genet 48(3):148–151PubMedCrossRefGoogle Scholar
  6. 6.
    Rosenberg M, Fuchs E, Le Beau MM, Eddy RL, Shows TB (1991) Three epidermal and one simple epithelial type II keratin genes map to human chromosome 12. Cytogenet Cell Genet 57(1):33–38PubMedCrossRefGoogle Scholar
  7. 7.
    Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40(5):403–439PubMedCrossRefGoogle Scholar
  8. 8.
    Alvarenga CA, Paravidino PI, Alvarenga M, Dufloth R, Gomes M, Zeferino LC, Schmitt F (2011) Expression of CK19 in invasive breast carcinomas of special histological types: implications for the use of one-step nucleic acid amplification. J Clin Pathol 64(6):493–497PubMedCrossRefGoogle Scholar
  9. 9.
    Effenberger KE, Borgen E, Eulenburg CZ, Bartkowiak K, Grosser A, Synnestvedt M, Kaaresen R, Brandt B, Nesland JM, Pantel K, Naume B (2011) Detection and clinical relevance of early disseminated breast cancer cells depend on their cytokeratin expression pattern. Breast Cancer Res Treat 125(3):729–738PubMedCrossRefGoogle Scholar
  10. 10.
    Boecker W, Moll R, Dervan P, Buerger H, Poremba C, Diallo RI, Herbst H, Schmidt A, Lerch MM, Buchwalow IB (2002) Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ. J Pathol 198(4):458–467PubMedCrossRefGoogle Scholar
  11. 11.
    Jones C, Ford E, Gillett C, Ryder K, Merrett S, Reis-Filho JS, Fulford LG, Hanby A, Lakhani SR (2004) Molecular cytogenetic identification of subgroups of grade III invasive ductal breast carcinomas with different clinical outcomes. Clin Cancer Res 10(18 Pt 1):5988–5997PubMedCrossRefGoogle Scholar
  12. 12.
    Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374PubMedCrossRefGoogle Scholar
  13. 13.
    Rakha EA, El-Sayed ME, Green AR, Paish EC, Lee AH, Ellis IO (2007) Breast carcinoma with basal differentiation: a proposal for pathology definition based on basal cytokeratin expression. Histopathology 50(4):434–438PubMedCrossRefGoogle Scholar
  14. 14.
    Reisenbichler ES, Balmer NN, Adams AL, Pfeifer JD, Hameed O (2011) Luminal cytokeratin expression profiles of breast papillomas and papillary carcinomas and the utility of a cytokeratin 5/p63/cytokeratin 8/18 antibody cocktail in their distinction. Mod Pathol 24(2):185–193PubMedCrossRefGoogle Scholar
  15. 15.
    Tan PH, Aw MY, Yip G, Bay BH, Sii LH, Murugaya S, Tse GM (2005) Cytokeratins in papillary lesions of the breast: is there a role in distinguishing intraductal papilloma from papillary ductal carcinoma in situ? Am J Surg Pathol 29(5):625–632PubMedCrossRefGoogle Scholar
  16. 16.
    van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, Torhorst J, Sauter G, Zuber M, Kochli OR, Mross F, Dieterich H, Seitz R, Ross D, Botstein D, Brown P (2002) Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 161(6):1991–1996PubMedCrossRefGoogle Scholar
  17. 17.
    Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14(5):1368–1376PubMedCrossRefGoogle Scholar
  18. 18.
    Cheng CW, Yu JC, Wang HW, Huang CS, Shieh JC, Fu YP, Chang CW, Wu PE, Shen CY (2010) The clinical implications of MMP-11 and CK-20 expression in human breast cancer. Clin Chim Acta 411(3–4):234–241PubMedCrossRefGoogle Scholar
  19. 19.
    Mehta R, Jain RK, Sneige N, Badve S, Resetkova E (2010) Expression of high-molecular-weight cytokeratin (34betaE12) is an independent predictor of disease-free survival in patients with triple-negative tumours of the breast. J Clin Pathol 63(8):744–747PubMedCrossRefGoogle Scholar
  20. 20.
    Wang SM, Huang DM, Li B, Ruan JD (2009) Association of CK20 expression with the progression, metastasis and prognosis of breast cancer. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 25(8):706–707PubMedGoogle Scholar
  21. 21.
    Rakha EA, Reis-Filho JS, Ellis IO (2010) Combinatorial biomarker expression in breast cancer. Breast Cancer Res Treat 120(2):293–308PubMedCrossRefGoogle Scholar
  22. 22.
    Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410PubMedCrossRefGoogle Scholar
  23. 23.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25(1):118–145PubMedCrossRefGoogle Scholar
  24. 24.
    Malzahn K, Mitze M, Thoenes M, Moll R (1998) Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas. Virchows Arch 433(2):119–129PubMedCrossRefGoogle Scholar
  25. 25.
    Delgallo WD, Rodrigues JR, Bueno SP, Viero RM, Soares CT (2010) Cell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinoma. Cytopathology 21(4):259–266PubMedCrossRefGoogle Scholar
  26. 26.
    Schem C, Maass N, Bauerschlag DO, Carstensen MH, Loning T, Roder C, Batic O, Jonat W, Tiemann K (2009) One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group. Virchows Arch 454(2):203–210PubMedCrossRefGoogle Scholar
  27. 27.
    Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, Kato Y, Tsuda H, Ueda S, Sato K, Tamaki Y, Noguchi S, Kataoka TR, Nakajima H, Komoike Y, Inaji H, Tsugawa K, Suzuki K, Nakamura S, Daitoh M, Otomo Y, Matsuura N (2007) One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 13(16):4807–4816PubMedCrossRefGoogle Scholar
  28. 28.
    Tot T (2000) The cytokeratin profile of medullary carcinoma of the breast. Histopathology 37(2):175–181, dPubMedCrossRefGoogle Scholar
  29. 29.
    Moriya T, Kozuka Y, Kanomata N, Tse GM, Tan PH (2009) The role of immunohistochemistry in the differential diagnosis of breast lesions. Pathology 41(1):68–76PubMedCrossRefGoogle Scholar
  30. 30.
    Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874PubMedCrossRefGoogle Scholar
  31. 31.
    Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 100(14):8418–8423PubMedCrossRefGoogle Scholar
  32. 32.
    Bankfalvi A, Ludwig A, De-Hesselle B, Buerger H, Buchwalow IB, Boecker W (2004) Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases. Mod Pathol 17(9):1051–1061PubMedCrossRefGoogle Scholar
  33. 33.
    Dawood S, Hu R, Homes MD, Collins LC, Schnitt SJ, Connolly J, Colditz GA, Tamimi RM (2011) Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat 126(1):185–192PubMedCrossRefGoogle Scholar
  34. 34.
    Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F (2005) p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch 447(4):688–694PubMedCrossRefGoogle Scholar
  35. 35.
    Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, Bishop T, Benitez J, Rivas C, Bignon YJ, Chang-Claude J, Hamann U, Cornelisse CJ, Devilee P, Beckmann MW, Nestle-Kramling C, Daly PA, Haites N, Varley J, Lalloo F, Evans G, Maugard C, Meijers-Heijboer H, Klijn JG, Olah E, Gusterson BA, Pilotti S, Radice P, Scherneck S, Sobol H, Jacquemier J, Wagner T, Peto J, Stratton MR, McGuffog L, Easton DF (2005) Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11(14):5175–5180PubMedCrossRefGoogle Scholar
  36. 36.
    Bhargava R, Beriwal S, McManus K, Dabbs DJ (2008) CK5 is more sensitive than CK5/6 in identifying the “basal-like” phenotype of breast carcinoma. Am J Clin Pathol 130(5):724–730PubMedCrossRefGoogle Scholar
  37. 37.
    Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R (2005) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24(29):4660–4671PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Mu-Min Shao
    • 1
  • Siu Ki Chan
    • 2
  • Alex M. C. Yu
    • 3
  • Christopher C. F. Lam
    • 3
  • Julia Y. S. Tsang
    • 3
  • Philip C. W. Lui
    • 5
  • Bonita K. B. Law
    • 6
  • Puay-Hoon Tan
    • 4
  • Gary M. Tse
    • 3
    • 7
  1. 1.Department of Pathology, Shenzhen Affiliated HospitalGuangzhou University of Traditional Chinese MedicineShenzhenChina
  2. 2.Department of PathologyKwongWah HospitalHongkongHong Kong
  3. 3.Department of Anatomical and Cellular PathologyPrince of Wales Hospital, The Chinese University of Hong KongHongkongHong Kong
  4. 4.Department of PathologySingapore General HospitalSingaporeSingapore
  5. 5.Department of PathologyUnion HospitalHongkongHong Kong
  6. 6.Breast CenterUnion HospitalHongkongHong Kong
  7. 7.Department of Anatomical and Cellular PathologyPrince of Wales HospitalHongkongHong Kong

Personalised recommendations