Skip to main content
Erschienen in: Breast Cancer 3/2014

01.05.2014 | Original Article

Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients

verfasst von: Kentaro Tamaki, Takanori Ishida, Nobumitsu Tamaki, Yoshihiko Kamada, Kanou Uehara, Minoru Miyashita, Masakazu Amari, Akiko Tadano-Sato, Yayoi Takahashi, Mika Watanabe, Keely McNamara, Noriaki Ohuchi, Hironobu Sasano

Erschienen in: Breast Cancer | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion.

Methods

We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index.

Results

There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and “20 % luminal A” in DFS (P = 0.039) but not between classical luminal A group and “25 % luminal A” (P = 0.105).

Conclusions

A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients.
Literatur
1.
Zurück zum Zitat Clahsen PC, van de Velde CJ, Duval C, Pallud C, Mandard AM, Delobelle-Deroide A, et al. The unit of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 1999;25:356–63.PubMedCrossRef Clahsen PC, van de Velde CJ, Duval C, Pallud C, Mandard AM, Delobelle-Deroide A, et al. The unit of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 1999;25:356–63.PubMedCrossRef
2.
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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
3.
Zurück zum Zitat Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst. 2011;103:1–9.CrossRef Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst. 2011;103:1–9.CrossRef
4.
Zurück zum Zitat Dressler LG, Seamer L, Owens MA, Clark GM, McGuire WL. Evaluation of a modeling system for S-phase estimation in breast cancer by flow cytometry. Cancer Res. 1987;47:5294–302.PubMed Dressler LG, Seamer L, Owens MA, Clark GM, McGuire WL. Evaluation of a modeling system for S-phase estimation in breast cancer by flow cytometry. Cancer Res. 1987;47:5294–302.PubMed
5.
Zurück zum Zitat Tovey SM, Witton CJ, Bartlett JM, Stanton PD, Reeves JR, Cooke TG. Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodoxyuridine labeling. Breast Cancer Res. 2004;6:246–51.CrossRef Tovey SM, Witton CJ, Bartlett JM, Stanton PD, Reeves JR, Cooke TG. Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodoxyuridine labeling. Breast Cancer Res. 2004;6:246–51.CrossRef
6.
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;3:13–20.CrossRef 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;3:13–20.CrossRef
7.
Zurück zum Zitat Lehr HA, Hansen DA, Kussick S, Li M, Hwang H, Krummenauer F, et al. Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count. Hum Pathol. 1999;30:1314–20.PubMedCrossRef Lehr HA, Hansen DA, Kussick S, Li M, Hwang H, Krummenauer F, et al. Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count. Hum Pathol. 1999;30:1314–20.PubMedCrossRef
8.
Zurück zum Zitat Tamaki K, Moriya T, Sato Y, Ishida T, Maruo Y, Yoshinaga K, et al. Vasohibn-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis. Cancer Sci. 2009;100:88–94.PubMedCrossRef Tamaki K, Moriya T, Sato Y, Ishida T, Maruo Y, Yoshinaga K, et al. Vasohibn-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis. Cancer Sci. 2009;100:88–94.PubMedCrossRef
9.
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 system, clinical parameters, and other prognostic factors-a surrogate marker? Cancer. 2003;97:1321–31.PubMedCrossRef Trihia H, Murray S, Price K, Gelber RD, Golouh R, Goldhirsch A, et al. Ki-67 expression in breast carcinoma: its association with grading system, clinical parameters, and other prognostic factors-a surrogate marker? Cancer. 2003;97:1321–31.PubMedCrossRef
10.
Zurück zum Zitat de Azambuja E, Cardoso F, de Castro G, Colozza M Jr, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96:1504–13.PubMedCentralPubMedCrossRef de Azambuja E, Cardoso F, de Castro G, Colozza M Jr, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96:1504–13.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef
12.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B. Panel members. 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.PubMedCentralPubMedCrossRef Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B. Panel members. 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.PubMedCentralPubMedCrossRef
13.
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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B. Panel members. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009. Ann Oncol. 2009;20:1319–29.PubMedCentralPubMedCrossRef Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B. Panel members. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009. Ann Oncol. 2009;20:1319–29.PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Tamaki K, Ishida T, Miyashita M, Amari M, Mori N, Ohuchi N, et al. Multidetector row helical computed tomography for invasive ductal carcinoma of breast: the correlation between radiological findings and the corresponding biological characteristic of the patients. Cancer Sci. 2012;103:67–72.PubMedCrossRef Tamaki K, Ishida T, Miyashita M, Amari M, Mori N, Ohuchi N, et al. Multidetector row helical computed tomography for invasive ductal carcinoma of breast: the correlation between radiological findings and the corresponding biological characteristic of the patients. Cancer Sci. 2012;103:67–72.PubMedCrossRef
16.
Zurück zum Zitat Tamaki K, Sasano H, Ishida T, Ishida K, Miyashita M, Takeda M, et al. Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients. Cancer Sci. 2010;101:2074–9.PubMedCrossRef Tamaki K, Sasano H, Ishida T, Ishida K, Miyashita M, Takeda M, et al. Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients. Cancer Sci. 2010;101:2074–9.PubMedCrossRef
17.
Zurück zum Zitat Tavassoli FA, Devilee P. World Health Organization classification of tumors. Tumor of the breast and female gential organs. Lyon: IARC; 2003. Tavassoli FA, Devilee P. World Health Organization classification of tumors. Tumor of the breast and female gential organs. Lyon: IARC; 2003.
18.
Zurück zum Zitat Rosen PP. Rosen’s breast pathology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2009. Rosen PP. Rosen’s breast pathology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2009.
19.
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
20.
Zurück zum Zitat Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. 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. 2007;25:118–45.PubMedCrossRef Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. 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. 2007;25:118–45.PubMedCrossRef
21.
Zurück zum Zitat Miyashita M, Ishida T, Ishida K, Tamaki K, Amari M, Watanabe M, et al. Histopathological subclassification of triple negative breast cancer using prognostic scoring system: five variables as candidates. Virchows Arch. 2011;458:65–72.PubMedCrossRef Miyashita M, Ishida T, Ishida K, Tamaki K, Amari M, Watanabe M, et al. Histopathological subclassification of triple negative breast cancer using prognostic scoring system: five variables as candidates. Virchows Arch. 2011;458:65–72.PubMedCrossRef
22.
Zurück zum Zitat Jalava P, Kuopio T, Juntti-Patinen L, Kotkansalo T, Kronqvist P, Collan Y. Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology. 2006;48:674–82.PubMedCrossRef Jalava P, Kuopio T, Juntti-Patinen L, Kotkansalo T, Kronqvist P, Collan Y. Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology. 2006;48:674–82.PubMedCrossRef
23.
Zurück zum Zitat Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A’Hern R, Salter J. Prognostic value of Ki67 expression after short term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007;99:167–70.PubMedCrossRef Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A’Hern R, Salter J. Prognostic value of Ki67 expression after short term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007;99:167–70.PubMedCrossRef
24.
Zurück zum Zitat Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A. Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol. 2009;20:628–35.PubMedCrossRef Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A. Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol. 2009;20:628–35.PubMedCrossRef
25.
Zurück zum Zitat Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J. Ki67 index, Her2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.PubMedCentralPubMedCrossRef Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J. Ki67 index, Her2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.PubMedCentralPubMedCrossRef
26.
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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Nishimura R, Okumura Y, Arima N. Trastuzumab monotherapy versus combination therapy for treating recurrence breast cancer: time to progression and survival. Breast Cancer. 2008;15:57–64.PubMedCrossRef Nishimura R, Okumura Y, Arima N. Trastuzumab monotherapy versus combination therapy for treating recurrence breast cancer: time to progression and survival. Breast Cancer. 2008;15:57–64.PubMedCrossRef
28.
Zurück zum Zitat Nishimura R, Arima N. Is triple negative a prognostic factor in breast cancer? Breast Cancer. 2008;15:303–8.PubMedCrossRef Nishimura R, Arima N. Is triple negative a prognostic factor in breast cancer? Breast Cancer. 2008;15:303–8.PubMedCrossRef
29.
Zurück zum Zitat Bhargava R, Striebel J, Beriwal S, Flickinger JC, Onisko A, Ahrendt G. Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers. Int J Clin Exp Pathol. 2009;2:444–55.PubMedCentralPubMed Bhargava R, Striebel J, Beriwal S, Flickinger JC, Onisko A, Ahrendt G. Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers. Int J Clin Exp Pathol. 2009;2:444–55.PubMedCentralPubMed
30.
Zurück zum Zitat Cuzick J, Dowsett M, Wale C. Prognostic value of a combined ER, PgR, Ki67, HER2 immunohistochemical (IHC4) score and comparison with the GHI recurrence score-results from TransATAC. Cancer Res. 2009;69:503s. Cuzick J, Dowsett M, Wale C. Prognostic value of a combined ER, PgR, Ki67, HER2 immunohistochemical (IHC4) score and comparison with the GHI recurrence score-results from TransATAC. Cancer Res. 2009;69:503s.
Metadaten
Titel
Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients
verfasst von
Kentaro Tamaki
Takanori Ishida
Nobumitsu Tamaki
Yoshihiko Kamada
Kanou Uehara
Minoru Miyashita
Masakazu Amari
Akiko Tadano-Sato
Yayoi Takahashi
Mika Watanabe
Keely McNamara
Noriaki Ohuchi
Hironobu Sasano
Publikationsdatum
01.05.2014
Verlag
Springer Japan
Erschienen in
Breast Cancer / Ausgabe 3/2014
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-012-0387-5

Weitere Artikel der Ausgabe 3/2014

Breast Cancer 3/2014 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

16.05.2024 Zielgerichtete Therapie Nachrichten

Trastuzumab deruxtecan scheint auch jenseits von Lungenkrebs gut gegen solide Tumoren mit HER2-Mutationen zu wirken. Dafür sprechen die Daten einer offenen Pan-Tumor-Studie.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.