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Original Article

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Blood Res 2016; 51(2):

Published online June 23, 2016

https://doi.org/10.5045/br.2016.51.2.127

© The Korean Society of Hematology

Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma

Tae-Dong Jeong1,2, Hyun-Sook Chi1*, Min-Sun Kim1, Seongsoo Jang1, Chan-Jeoung Park1, and Joo Ryung Huh3

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1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

2Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, Korea.

3Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to : Correspondence to Hyun-Sook Chi, M.D., Ph.D. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. hschi4502@gmail.com

Received: January 15, 2016; Revised: March 14, 2016; Accepted: March 31, 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background

A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings.

Methods

Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined.

Results

Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11–20% in 14 patients, 21–30% in 3 patients, 31–40% in 4 patients, 41–50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033).

Conclusion

The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.

Keywords Bone marrow, Ki-67 proliferation index, Mantle cell lymphoma, Prognosis

Article

Original Article

Blood Res 2016; 51(2): 127-132

Published online June 23, 2016 https://doi.org/10.5045/br.2016.51.2.127

Copyright © The Korean Society of Hematology.

Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma

Tae-Dong Jeong1,2, Hyun-Sook Chi1*, Min-Sun Kim1, Seongsoo Jang1, Chan-Jeoung Park1, and Joo Ryung Huh3

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

2Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, Korea.

3Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to: Correspondence to Hyun-Sook Chi, M.D., Ph.D. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. hschi4502@gmail.com

Received: January 15, 2016; Revised: March 14, 2016; Accepted: March 31, 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

A high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings.

Methods

Immunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined.

Results

Of the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11–20% in 14 patients, 21–30% in 3 patients, 31–40% in 4 patients, 41–50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033).

Conclusion

The 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.

Keywords: Bone marrow, Ki-67 proliferation index, Mantle cell lymphoma, Prognosis

Fig 1.

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Figure 1.

Overall survival according to the Ki-67 proliferation index (PI). (A) A cut-off of 20% reveals significant differences in survival, regardless of bone marrow findings (N=56, P=0.034). (B) In patients with bone marrow involvement of mantle cell lymphoma, a cut-off of 30% is statistically significant (N=39, P=0.033).

Blood Research 2016; 51: 127-132https://doi.org/10.5045/br.2016.51.2.127

Fig 2.

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Figure 2.

Comparison of Ki-67 immunohistochemical staining results between tissue and bone marrow biopsies. A good correlation is observed between tissue biopsy with a Ki-67 PI <30% and bone marrow biopsy results (Spearman's correlation coefficient=0.559, P=0.024).

Blood Research 2016; 51: 127-132https://doi.org/10.5045/br.2016.51.2.127
Baseline characteristics of the study population.

Abbreviations: 1Q, first quartile; 3Q, third quartile; BM, bone marrow; CI, confidence interval; HR, hazard ratio; LDH, lactate dehydrogenase; NA, not available; WBC, white blood cells..
Clinical outcomes of 54 patients with mantle cell lymphoma according to cytomorphological variant.

a)Fisher's exact test, b)Mann Whitney U Test, c)Cox proportional hazard model..

Abbreviations: WBC, white blood cell; LDH, lactate dehydrogenase; CI, confidence interval..
Determination of the cut-off value for the Ki-67 proliferation indices in all patients (N=56).

a)Cox proportional hazard model..

Abbreviations: MCL, mantle cell lymphoma; RR, relative hazard ratio; CI, confidence interval..
Determination of the cut-off value for the Ki-67 proliferation indices in patients with bone marrow involvement of mantle cell lymphoma (N=39).

a)Cox proportional hazard model..

Abbreviations: MCL, mantle cell lymphoma; RR, relative hazard ratio; CI, confidence interval..
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