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Erschienen in: Breast Cancer 2/2015

01.03.2015 | Original Article

Visual assessment of Ki67 at a glance is an easy method to exclude many luminal-type breast cancers from counting 1000 cells

verfasst von: Akira I. Hida, Yumi Oshiro, Hiromichi Inoue, Hidetoshi Kawaguchi, Natsumi Yamashita, Takuya Moriya

Erschienen in: Breast Cancer | Ausgabe 2/2015

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Abstract

Background

The Ki67 labeling index (LI) reflects the proliferative activity of breast cancers and defines luminal A and B tumors; however, no detailed method to measure Ki67 has been standardized. Here, we propose a fast and easy way to evaluate Ki67.

Methods

Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67 (MIB-1) was performed on 235 primary invasive ductal carcinomas. For each sample, a hot spot with many Ki67+ cells was identified using a low-power field (40×, 4× objective). Three independent areas in high-power field (400×) were selected at the hot spot, and all cancer cells in the 3 areas were manually counted to calculate LI (% Ki67+ cells). Alternatively, micrographs taken at 100× and 200× fields including the hot spot were shown to 2 pathologists, who visually assessed percentages of Ki67+ cells in 10 % intervals at a glance (Eye-10).

Results

Eye-10 and LI were strongly correlated (r = 0.9412, P < 0.0001). All cases of Eye-10 ≥ 30 % had LI > 14 %; most of those <10 % had LI < 14 %. Of 170 ER+/HER2− tumors, Eye-10-based subtypes matched 87 % of LI-driven subtypes, and interobserver agreement was good (κ = 0.705).

Conclusion

Eye-10 is far easier than counting many cancer cells and useful for classifying breast cancers. Eye-10 can exclude obviously high and low Ki67 cases, leaving a “gray zone” around a cutoff point. Combining Eye-10 and manual counting is a good candidate for a standard method to evaluate Ki67.
Literatur
2.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. 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. 2011;22:1736–47. doi:10.1093/annonc/mdr304.CrossRefPubMedCentralPubMed Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. 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. 2011;22:1736–47. doi:10.​1093/​annonc/​mdr304.CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–68.PubMed Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–68.PubMed
5.
6.
Zurück zum Zitat Hammond ME, Hayes DF, Wolff AC. Clinical Notice for American Society of Clinical Oncology-College of American Pathologists guideline recommendations on ER/PgR and HER2 testing in breast cancer. J Clin Oncol. 2011;29:e458. doi:10.1200/JCO.2011.35.2245.CrossRefPubMed Hammond ME, Hayes DF, Wolff AC. Clinical Notice for American Society of Clinical Oncology-College of American Pathologists guideline recommendations on ER/PgR and HER2 testing in breast cancer. J Clin Oncol. 2011;29:e458. doi:10.​1200/​JCO.​2011.​35.​2245.CrossRefPubMed
7.
Zurück zum Zitat Spyratos F, Ferrero-Pous M, Trassard M, Hacene K, Phillips E, Tubiana-Hulin M, et al. Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer. 2002;94:2151–9. doi:10.1002/cncr.10458.CrossRefPubMed Spyratos F, Ferrero-Pous M, Trassard M, Hacene K, Phillips E, Tubiana-Hulin M, et al. Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer. 2002;94:2151–9. doi:10.​1002/​cncr.​10458.CrossRefPubMed
8.
Zurück zum Zitat Nishimura R, Osako T, Okumura Y, Tashima R, Toyozumi Y, Arima N. Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosis. World J Surg Oncol. 2011;9:131. doi: 10.1186/1477-7819-9-131. Nishimura R, Osako T, Okumura Y, Tashima R, Toyozumi Y, Arima N. Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosis. World J Surg Oncol. 2011;9:131. doi: 10.​1186/​1477-7819-9-131.
10.
Zurück zum Zitat Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst. 2008;100:207–12. doi:10.1093/jnci/djm289.CrossRefPubMed Viale G, Regan MM, Mastropasqua MG, Maffini F, Maiorano E, Colleoni M, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst. 2008;100:207–12. doi:10.​1093/​jnci/​djm289.CrossRefPubMed
11.
Zurück zum Zitat Ellis MJ, Tao Y, Luo J, A’Hern R, Evans DB, Bhatnagar AS, et al. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008;100:1380–8. doi:10.1093/jnci/djn309.CrossRefPubMedCentralPubMed Ellis MJ, Tao Y, Luo J, A’Hern R, Evans DB, Bhatnagar AS, et al. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008;100:1380–8. doi:10.​1093/​jnci/​djn309.CrossRefPubMedCentralPubMed
12.
Zurück zum Zitat Nishimura R, Osako T, Okumura Y, Hayashi M, Arima N. Clinical significance of Ki-67 in neoadjuvant chemotherapy for primary breast cancer as a predictor for chemosensitivity and for prognosis. Breast Cancer. 2010;17:269–75. doi:10.1007/s12282-009-0161-5.CrossRefPubMed Nishimura R, Osako T, Okumura Y, Hayashi M, Arima N. Clinical significance of Ki-67 in neoadjuvant chemotherapy for primary breast cancer as a predictor for chemosensitivity and for prognosis. Breast Cancer. 2010;17:269–75. doi:10.​1007/​s12282-009-0161-5.CrossRefPubMed
13.
Zurück zum Zitat DeCensi A, Guerrieri-Gonzaga A, Gandini S, Serrano D, Cazzaniga M, Mora S, et al. Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer. Ann Oncol. 2011;22:582–7. doi:10.1093/annonc/mdq427.CrossRefPubMed DeCensi A, Guerrieri-Gonzaga A, Gandini S, Serrano D, Cazzaniga M, Mora S, et al. Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer. Ann Oncol. 2011;22:582–7. doi:10.​1093/​annonc/​mdq427.CrossRefPubMed
14.
Zurück zum Zitat Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011;29:4273–8. doi:10.1200/JCO.2010.31.2835.CrossRefPubMed Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011;29:4273–8. doi:10.​1200/​JCO.​2010.​31.​2835.CrossRefPubMed
15.
Zurück zum Zitat Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13–20.CrossRefPubMed Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13–20.CrossRefPubMed
19.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95. doi:10.1200/JCO.2009.25.6529.CrossRefPubMedCentralPubMed Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95. doi:10.​1200/​JCO.​2009.​25.​6529.CrossRefPubMedCentralPubMed
20.
Zurück zum Zitat Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, et al. Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors—a surrogate marker? Cancer. 2003;97:1321–31. doi:10.1002/cncr.11188.CrossRefPubMed Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, et al. Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors—a surrogate marker? Cancer. 2003;97:1321–31. doi:10.​1002/​cncr.​11188.CrossRefPubMed
21.
Zurück zum Zitat Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell’Orto P, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1–98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 2008;26:5569–75. doi:10.1200/JCO.2008.17.0829.CrossRefPubMedCentralPubMed Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell’Orto P, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1–98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 2008;26:5569–75. doi:10.​1200/​JCO.​2008.​17.​0829.CrossRefPubMedCentralPubMed
22.
Zurück zum Zitat Endo Y, Toyama T, Takahashi S, Sugiura H, Yoshimoto N, Iwasa M, et al. High estrogen receptor expression and low Ki67 expression are associated with improved time to progression during first-line endocrine therapy with aromatase inhibitors in breast cancer. Int J Clin Oncol. 2011;16:512–8. doi:10.1007/s10147-011-0215-5.CrossRefPubMed Endo Y, Toyama T, Takahashi S, Sugiura H, Yoshimoto N, Iwasa M, et al. High estrogen receptor expression and low Ki67 expression are associated with improved time to progression during first-line endocrine therapy with aromatase inhibitors in breast cancer. Int J Clin Oncol. 2011;16:512–8. doi:10.​1007/​s10147-011-0215-5.CrossRefPubMed
24.
26.
28.
Zurück zum Zitat Gudlaugsson E, Skaland I, Janssen EA, Smaaland R, Shao Z, Malpica A, et al. Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer. Histopathology. 2012;. doi:10.1111/j.1365-2559.2012.04329.x.PubMed Gudlaugsson E, Skaland I, Janssen EA, Smaaland R, Shao Z, Malpica A, et al. Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer. Histopathology. 2012;. doi:10.​1111/​j.​1365-2559.​2012.​04329.​x.PubMed
Metadaten
Titel
Visual assessment of Ki67 at a glance is an easy method to exclude many luminal-type breast cancers from counting 1000 cells
verfasst von
Akira I. Hida
Yumi Oshiro
Hiromichi Inoue
Hidetoshi Kawaguchi
Natsumi Yamashita
Takuya Moriya
Publikationsdatum
01.03.2015
Verlag
Springer Japan
Erschienen in
Breast Cancer / Ausgabe 2/2015
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-013-0460-8

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