SSTR2 expression in EBV-positive and EBV-negative lymphomas.

[BACKGROUND] Somatostatin receptor 2 (SSTR2) protein expression is aberrantly upregulated in various tumors and can be visualized using scintigraphy or radiological techniques and therapeutically targeted using octreotide-based molecules.

[PURPOSE] In this study, we assessed SSTR2 expression in the largest cohort of hematopoietic proliferations examined to date and interrogated the relationship between EBV and SSTR2 in EBV-associated lymphomas as a possible mechanism for SSTR2 upregulation.

[METHODS] We retrospectively identified 407 cases of lymphoma from Guatemala, a country with a high prevalence of EBV-associated lymphomas. SSTR2 protein expression was assessed by immunohistochemistry, while EBV was assessed by in situ hybridization for EBV-associated small RNAs.

[RESULTS] We found SSTR2 expression in 43% (20/47) of EBV-positive classic Hodgkin lymphomas (cHL) and 0% (0/12) of EBV-negative cHL cases. All but one of the other EBV-associated lymphomas (n = 53) were negative for SSTR2. Within the EBV-negative non-Hodgkin lymphomas assessed, 33% (1/3) of diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma (HGBL) with MYC and BCL2 rearrangement, 17% (25/149) of DLBCL not otherwise specified, and 17% (5/29) of follicular lymphomas showed SSTR2 expression. All other lymphomas showed no significant SSTR2 expression.

[CONCLUSIONS] Our study demonstrates that EBV infection is required, but not sufficient, to upregulate SSTR2 in classic Hodgkin lymphoma, but not in other EBV-associated lymphomas. We also provide data to suggest that SSTR2 is associated with "higher-grade" germinal center-derived B-cell lymphomas in EBV-negative non-Hodgkin lymphomas.