Expression of the novel tumour suppressor sterile alpha motif and HD domain-containing protein 1 is an independent adverse prognostic factor in classical Hodgkin lymphoma

Br J Haematol. 2021 May;193(3):488-496. doi: 10.1111/bjh.17352. Epub 2021 Feb 2.

Abstract

The expression patterns and prognostic significance of sterile alpha motif and HD domain-containing protein 1 (SAMHD1) protein in the neoplastic Hodgkin and Reed Sternberg (HRS) cells of Hodgkin lymphoma (HL) were investigated in a cohort of 154 patients with HL treated with standard regimens. SAMHD1 expression was assessed by immunohistochemistry using diagnostic lymph node biopsies obtained prior to treatment. Using an arbitrary 20% cut-off, SAMHD1 was positive in HRS cells of 48/154 (31·2%) patients. SAMHD1 expression was not associated with clinicopathologic parameters, such as age, gender, stage or histologic subtype. In 125 patients with a median follow-up of 90 months (7-401 months), SAMHD1 expression in HRS cells significantly correlated with inferior freedom from progression (FFP) (P = 0·025), disease-specific survival (DSS) (P = 0·013) and overall survival (OS) (P = 0·01). Importantly, in multivariate models together with disease stage, histology subtype and type of treatment as covariates, SAMHD1 expression retained an independent significant association with unfavourable FFP (P = 0·005) as well as DSS (P = 0·022) and OS (P = 0·018). These findings uncover the significance of a novel, adverse prognostic factor in HL that may have therapeutic implications since SAMHD1 inhibitors are now available for clinical use.

Keywords: Hodgkin lymphoma; SAMHD1; prognosis.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bleomycin / administration & dosage
  • Cell Line, Tumor
  • Dacarbazine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hodgkin Disease* / drug therapy
  • Hodgkin Disease* / enzymology
  • Hodgkin Disease* / mortality
  • Humans
  • Lymph Nodes / enzymology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • SAM Domain and HD Domain-Containing Protein 1 / biosynthesis*
  • Survival Rate
  • Vinblastine / administration & dosage

Substances

  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human

Supplementary concepts

  • ABVD protocol