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Prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma

Tomoki Motegi DVM, PhD1, Hirotaka Tomiyasu DVM, PhD2, Yuko Goto-Koshino DVM, PhD3, Masashi Takahashi DVM, PhD4, Saaya Hiyoshi-Kanemoto DVM, PhD5, Yasuhito Fujino DVM, PhD6, Koichi Ohno DVM, PhD7, and Hajime Tsuimoto DVM, PhD8
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  • 1 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.
  • | 2 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.
  • | 3 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.
  • | 4 Laboratory of Small Animal Internal Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan 890-0065.
  • | 5 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.
  • | 6 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.
  • | 7 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.
  • | 8 Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan 113-8657.

Abstract

OBJECTIVE To determine the prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma (BCL).

ANIMALS 45 dogs with multicentric BCL and 10 healthy control Beagles.

PROCEDURES The medical record database of a veterinary teaching hospital was searched to identify dogs with BCL that were treated between November 2005 and April 2015. Information regarding overall response to chemotherapy, progression-free survival (PFS) time, and overall survival time was extracted from each record. Archived lymph node aspirate specimens from dogs with BCL and lymph node aspirate specimens from the 10 control dogs underwent real-time PCR analysis to determine mRNA expression of CD44 variant isoforms of exons 3, 6, and 7 and the CD44 whole isoform. For each isoform, mRNA expression was compared between dogs with BCL and control dogs. The mean relative expression of each isoform was used to classify dogs with BCL into either a high- or low-expression group, and overall response rate, PFS time, and overall survival time (ie, indices of prognosis) were compared between the 2 groups.

RESULTS For all isoforms evaluated, mean relative mRNA expression for dogs with BCL was numerically lower than that for control dogs. Dogs with BCL and high CD44 isoform expression had a lower overall response rate, median PFS time, and median overall survival time, compared with dogs with BCL and low CD44 isoform expression.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for dogs with BCL, high expression of exons 3, 6, and 7 was associated with a poor prognosis.

Abstract

OBJECTIVE To determine the prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma (BCL).

ANIMALS 45 dogs with multicentric BCL and 10 healthy control Beagles.

PROCEDURES The medical record database of a veterinary teaching hospital was searched to identify dogs with BCL that were treated between November 2005 and April 2015. Information regarding overall response to chemotherapy, progression-free survival (PFS) time, and overall survival time was extracted from each record. Archived lymph node aspirate specimens from dogs with BCL and lymph node aspirate specimens from the 10 control dogs underwent real-time PCR analysis to determine mRNA expression of CD44 variant isoforms of exons 3, 6, and 7 and the CD44 whole isoform. For each isoform, mRNA expression was compared between dogs with BCL and control dogs. The mean relative expression of each isoform was used to classify dogs with BCL into either a high- or low-expression group, and overall response rate, PFS time, and overall survival time (ie, indices of prognosis) were compared between the 2 groups.

RESULTS For all isoforms evaluated, mean relative mRNA expression for dogs with BCL was numerically lower than that for control dogs. Dogs with BCL and high CD44 isoform expression had a lower overall response rate, median PFS time, and median overall survival time, compared with dogs with BCL and low CD44 isoform expression.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for dogs with BCL, high expression of exons 3, 6, and 7 was associated with a poor prognosis.

Supplementary Materials

    • Supplementary Table S1 (PDF 152 kb)

Contributor Notes

Dr. Motegi's present address is Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, 1-7-22 Suehiro-cho, Kanagawa, Japan 230-0045.

Address correspondence to Dr. Tsuimoto (atsuji@mail.ecc-u-tokyo.ac.jp).