Possible New Histological Prognostic Index for Large B-Cell Lymphoma

Author:

Nitta Hideaki1ORCID,Takizawa Haruko1,Mitsumori Toru1,Iizuka-Honma Hiroko1,Araki Yoshihiko2ORCID,Fujishiro Maki3,Tomita Shigeki4,Kishikawa Satsuki4,Hashizume Akane4,Sawada Tomohiro5,Okubo Mitsuo6,Sekiguchi Yasunobu7,Ando Miki8,Noguchi Masaaki1

Affiliation:

1. Department of Hematology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu-shi 279-0021, Japan

2. Department of Pathology and Microbiology, Division of Microbiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan

3. Institute for Environmental and Gender-Specific Medicine, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan

4. Department of Diagnostic Pathology, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan

5. Department of Clinical Laboratory, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan

6. Laboratory of Blood Transfusion, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan

7. Hematology Clinic, Saitama Cancer Center, Saitama 362-0806, Japan

8. Division of Hematology, Juntendo University Juntendo Hospital, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

We conducted a retrospective analysis of GRP94 immunohistochemical (IHC) staining, an ER stress protein, on large B-cell lymphoma (LBCL) cells, intracellular p53, and 15 factors involved in the metabolism of the CHOP regimen: AKR1C3 (HO metabolism), CYP3A4 (CHOP metabolism), and HO efflux pumps (MDR1 and MRP1). The study subjects were 42 patients with LBCL at our hospital. The IHC staining used antibodies against the 17 factors. The odds ratios by logistic regression analysis used a dichotomous variable of CR and non-CR/relapse were statistically significant for MDR1, MRP1, and AKR1C3. The overall survival (OS) after R-CHOP was compared by the log-rank test. The four groups showed that Very good (5-year OS, 100%) consisted of four patients who showed negative IHC staining for both GRP94 and CYP3A4. Very poor (1-year OS, 0%) consisted of three patients who showed positive results in IHC for both GRP94 and CYP3A4. The remaining 35 patients comprised two subgroups: Good (5-year OS 60–80%): 15 patients who showed negative staining for both MDR1 and AKR1C3 and Poor (5-year OS, 10–20%): 20 patients who showed positive staining for either MDR, AKR1C3, MRP1, or p53. The Histological Prognostic Index (HPI) (the four groups: Very poor, Poor, Good, and Very good) is a breakthrough method for stratifying patients based on the factors involved in the development of treatment resistance.

Publisher

MDPI AG

Subject

General Medicine

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