Analysis of membranous Ki-67 staining in breast cancer and surrounding breast epithelium
- 131 Downloads
Membranous Ki-67 staining with the MIB-1 antibody has been described in hyalinising trabecular adenomas of the thyroid and sclerosing haemangiomas of the lung. Its relatively rare occurrence in breast tumours has also been documented. The aim of the present study was to assess the rate of any membranous MIB-1 staining in breast specimens. The staining was performed at room temperature with 1:100 dilution of the antibody. One hundred four core needle biopsies and 41 operative specimens were analysed. Membranous staining was noted in 36/144 invasive carcinomas, 20/42 in situ carcinomas and 46/99 cases of peritumoural benign/normal breast epithelium. Most often, it presented as focal and partial polarised luminal membranous staining although complete circumferential staining also occurred, and membranous labelling was sometimes accompanied by cytoplasmic staining, too. In a few cases tested, greater dilution of the primary antibody did not abolish the membranous staining, which was absent with the SP6 monoclonal Ki-67 antibody. The membranous staining of invasive tumours showed no association with histological grade, lumen formation, oestrogen or progesterone receptor status or the Ki-67 nuclear labelling. In contrast, it was associated with a HER2-positive status, although it occurred in all molecular subtypes approached by immunohistochemistry. The background of this membranous staining remains elusive. It is unlikely to represent an artefact. At least partial sharing of an epitope of the nuclear Ki-67 protein with an unidentified membranous protein and some functional differences between membranous staining producing tumours and tumours lacking this pattern of staining may both contribute to some extent.
KeywordsBreast cancer Ki-67 MIB-1 Membranous staining Immunohistochemistry HER2
The author of the manuscript made substantial contributions to the following:
- the conception/design of the work; the acquisition, analysis, interpretation of data for the work;
- drafting the work and/or revising it critically for important intellectual content;
- final approval of the version submitted for publication; and
- agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Other contribution is acknowledged in the Funding section of the manuscript.
This study was partially funded by the National Research, Development and Innovation Office grant GINOP-2.3.2-15-2016-00020.
Compliance with ethical standards
The author has consulted the journal policy regarding compliance with ethical standards and state that accepted principles of ethical and professional conduct have been followed. The author includes information regarding sources of funding and potential conflicts of interest (financial or non-financial) (next section). Ethical approval and informed consent-related information (waiver for this particular study) are summarised in the final paragraph of the “Materials and methods” section. The study did not include animals; therefore, issues relating to animal welfare do not apply.
Conflict of interest
The author declares that he has no conflict of interest.
- 1.Gerdes J, Li L, Schlueter C, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138:867–873PubMedPubMedCentralGoogle Scholar
- 5.Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel members (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–1747CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ (2013) Panel members (2013) personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol 24:2206–2223CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Gándara-Cortes M, Vázquez-Boquete Á, Fernández-Rodríguez B, Viaño P, Ínsua D, Seoane-Seoane A, Gude F, Gallego R, Fraga M, Antúnez JR, Curiel T, Pérez-López E, García-Caballero T (2018) Breast cancer subtype discrimination using standardized 4-IHC and digital image analysis. Virchows Arch 472:195–203. https://doi.org/10.1007/s00428-017-2194-z
- 8.Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, Mcshane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JA, Hayes DF, International Ki-67 in Breast Cancer Working Group (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Laenkholm AV, Grabau D, Møller Talman ML, Balslev E, Bak Jylling AM, Tabor TP, Johansen M, Brügmann A, Lelkaitis G, Di Caterino T, Mygind H, Poulsen T, Mertz H, Søndergaard G, Bruun Rasmussen B (2018) An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG). Acta Oncol 57:83–89CrossRefPubMedGoogle Scholar
- 15.Varga Z, Diebold J, Dommann-Scherrer C, Frick H, Kaup D, Noske A, Obermann E, Ohlschlegel C, Padberg B, Rakozy C, Sancho Oliver S, Schobinger-Clement S, Schreiber-Facklam H, Singer G, Tapia C, Wagner U, Mastropasqua MG, Viale G, Lehr HA (2012) How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss Working Group of Breast- and Gynecopathologists. PLoS One 7:e37379CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Cserni G, Vörös A, Liepniece-Karele I, Bianchi S, Vezzosi V, Grabau D, Sapino A, Castellano I, Regitnig P, Foschini MP, Zolota V, Varga Z, Figueiredo P, Decker T, Focke C, Kulka J, Kaya H, Reiner-Concin A, Amendoeira I, Callagy G, Caffrey E, Wesseling J, Wells C (2014) Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values. Breast 23:259–263CrossRefPubMedGoogle Scholar
- 17.Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med 134:e48–e72PubMedGoogle Scholar
- 19.Cserni G, Chmielik E, Cserni B, Tot T (2018) The new TNM-based staging of breast cancer. Virchows Arch. https://doi.org/10.1007/s00428-018-2301-9
- 21.Niemiec J, Adamczyk A, Ambicka A, Mucha-Małecka A, Wysocki WM, Majchrzyk K, Ryś J (2015) BGX-Ki-67 index as a supplementary marker to MIB-1 index, enabling more precise distinction between luminal A and B subtypes of breast carcinoma and eliminating the problem of membranous/cytoplasmic MIB-1 staining. Am J Clin Pathol 143:419–429CrossRefPubMedGoogle Scholar
- 23.https://www.ncbi.nlm.nih.gov/protein (Accessed 03 Mar 2018)