DOI: https://doi.org/10.22263/2312-4156.2025.1.79
D.A. Davydov, E.P. Shupilova, I.Y. Zherka, A.S. Petuhova, A.F. Mahilyanchik, A.S. Portyanko
Various prognostic value of proliferative activity index in primary and recurrent B-cell non-Hodgkin’s lymphomas
N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Republic of Belarus
Vestnik VGMU. 2025;24(1):79-88.
Abstract.
Objectives. To determine the prognostic value of the proliferative activity index in primary and recurrent B-cell non-Hodgkin`s lymphomas.
Material and methods. 108 patients with histologically verified recurrent B-NHL were included in the study. Regression analysis was performed to assess the prognostic value of the studied factors.
Results. In 13% of cases, clinical and radiological relapse was accompanied by the detection of B-NHL nosological form different from the primary tumor. Patients with aggressive primary B-NHL and low IPA have been established to have earlier disease relapse compared to patients with high IPA. Patients with indolent primary tumors and high IPA had earlier disease recurrence than patients with low IPA.
Conclusions. High IPA in aggressive recurrent B-NHL is associated with an increased risk of disease progression by 4.8 times, death by 2.5 times. For indolent recurrent B-NHL with high IPA values, the risk of disease progression increases by 2.8 times, death by 2.5 times.
Keywords: non-Hodgkin`s lymphomas, proliferation index, relapse, clinical and morphological features, resistance.
References
1. Kaprin AD, Starinskiy VV, Shakhzadova AO, red. Malignant neoplasms in Russia in 2020 (morbidity and mortality). Moscow, RF; 2021. 252 р. (In Russ.)
2. Siegel RL, Miller KD, Jemal A. Cancer statistic, 2020. CA: A Cancer Journal for Clinicians. 2020 Jan;70(1):7-30. doi: http://dx.doi.org/10.3322/caac.21590
3. Okeanov AE, Moiseev PI, Levin LF, Evmenenko AA, Ipatiy TB; Polyakov SL, red. Rak v Belarusi: tsifry i fakty. Cancer in Belarus: figures and facts. Analysis of the data of the Belarusian Cancer Registry for 2010-2019. Minsk, RB: RNPTs OMR im NN Aleksandrova; 2020. 298 р. (In Russ.)
4. Larouche J-F, Berger F, Chassagne-Clément C, Ffrench M, Callet-Bauchu E, Sebban C, et al. Lymphoma Recurrence 5 Years or Later Following Diffuse Large B-Cell Lymphoma: Clinical Characteristics and Outcome. Journal of Clinical Oncology. 2010 Apr;28(12):2094-20100. doi: http://dx.doi.org/10.1200/JCO.2009.24.5860
5. Maurer MJ, Ghesquière H, Jais J-P, Witzig TE, Haioun C, Thompson CA, et al. Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy. Journal of Clinical Oncology. 2014 Apr;32(10):1066-1073. doi: http://dx.doi.org/10.1200/JCO.2013.51.5866
6. Kesireddy M, Lunning M. Relapsed or Refractory Diffuse Large B-Cell Lymphoma: «Dazed and Confused». Oncology (Williston Park). 2022 Jun;36(6):366-375. doi: http://dx.doi.org/10.46883/2022.25920963
7. Zhu X, Chen L, Huang B, Wang Y, Ji L, Wu J, et al. The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Scientific Reports. 2020 Jan;10(1):225. doi: http://dx.doi.org/10.1038/s41598-019-57094-3
8. He X, Chen Z, Fu T, Jin X, Yu T, Liang Y, et al. Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis. BMC Cancer. 2014 Mar:14:153. doi: http://dx.doi.org/10.1186/1471-2407-14-153
9. Sales Gil R, Vagnarelli P. Ki-67: More Hidden behind a ‘Classic Proliferation Marker’. Trends in Biochemical Science. 2018 Oct;43(10):747-748. doi: http://dx.doi.org/10.1016/j.tibs.2018.08.004
10. Jianmin Han, Chad M McCall, Scott Isom, Wesley Smith, Dakota Jenneman, Stephanie Begley, et al. High Ki67 Index Is Associated with Shorter Progression Free Survival in Follicular Lymphoma Patients Treated with Frontline Immunochemotherapy. Blood. 2023;142(Suppl 1):4385. doi: http://dx.doi.org/10.1182/blood-2023-180106
11. Miller TP, Grogan TM, Dahlberg S, Spier CM, Braziel RM, Banks PM, et al. Prognostic Significance of the Ki-67 -Associated Proliferative Antigen in Aggressive Non-Hodgkin’s Lymphomas: A Prospective Southwest Oncology Group Tria. Blood. 1994 Mar;83(6):1460-1466.
12. Hashmi AA, Iftikhar SN, Nargus G, Ahmed O, Asghar IA, Shirazi UA, et al. Ki67 Proliferation Index in Germinal and Non-Germinal Subtypes of Diffuse Large B-Cell Lymphoma. Cureus. 2021 Feb;13(2):e13120. doi: http://dx.doi.org/10.7759/cureus.13120
13. Zaiem Feras, Jerbi R, Albanyan O, Puccio J, Kafri Z, Yang J, et al. High Ki67 proliferation index but not cell-of-origin subtypes is associatedwith shorter overall survival in diffuse large B-cell lymphoma. Avicenna Journal of Medicine. 2020 Oct;10(4):241-248. doi: http://dx.doi.org/10.4103/ajm.ajm_81_20
14. Li Z-M, Huang J-J, Xia Y, Zhu Y-J, Zhao W, Wei W-X, et al. High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy. European Journal of Haematology. 2012 Jun;88(6):510-517. doi: http://dx.doi.org/10.1111/j.1600-0609.2012.01778.x
15. Nichols MM, Ondrejka SL, Patil S, Durkin L, Hill BT, Hsi ED. Ki67 proliferation index in follicular lymphoma is associated with favorable outcome in patients treated with R-CHOP. Leukemia and Lymphoma. 2023 Jul-Aug;64(8):1433-1441. doi: http://dx.doi.org/10.1080/10428194.2023.2214651
16. Xue T, Yu B-H, Yan W-H, Jiang X-N, Tian T, Zhou X-Y, et al. Prognostic significance of histologic grade and Ki-67 proliferation index in follicular lymphoma. Hematological Oncology. 2020 Dec;38(5):665-672. doi: http://dx.doi.org/10.1002/hon.2778
17. Yamamoto E, Tomita N, Sakata S, Tsuyama N, Takeuchi K, Nakajima Y, et al. MIB-1 labeling index as a prognostic factor for patients with follicular lymphoma treated with rituximab plus CHOP therapy. Cancer Science. 2013 Dec;104(12):1670-1674. doi: http://dx.doi.org/10.1111/cas.12288
18. Kedmi M, Hedvat CV, Maragulia J, Zhang Z, Zelenetz AD. Association of quantitative assessment of the intrafollicular proliferation index with outcome in follicular lymphoma. British Journal of Haematology. 2014 Mar;164(5):646-652. doi: http://dx.doi.org/10.1111/bjh.12667
Submitted 14.10.2024
Accepted 11.02.2025
Information about authors:
D.A. Davydov – Candidate of Medical Sciences, head of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus.
e-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Denis A. Davydov;
E.P. Shupilova – researcher of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus.
I.Y. Zherka – Candidate of Medical Sciences, senior researcher of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus, https://orcid.org/0000-0002-5134-3666
A.S. Petuhova – biologist of the Oncology Department of Immunomorphology and Proteomics, N.N. Alexandrov National Cancer Centre of Belarus.
A.F. Mahilyanchik – junior researcher of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus.
A.S. Portyanko – Doctor of medical sciences, head of the Republican Molecular Genetic Laboratory of Carcinogenesis, N.N. Alexandrov National Cancer Centre of Belarus.
