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

Tae-Dong Jeong; Hyun-Sook Chi; Min-Sun Kim; Seongsoo Jang; Chan-Jeoung Park; Joo Ryung Huh

doi:10.5045/br.2016.51.2.127

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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

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

Tae-Dong Jeong^1,2, Hyun-Sook Chi^1*, 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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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

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

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

Tae-Dong Jeong^1,2, Hyun-Sook Chi^1*, 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

Abstract

Background

Methods

Results

Conclusion

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

Abstract

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

Table 1 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..

Table 2 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..

Table 3 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..

Table 4 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..