Refined prognostic role of CD68-positive tumor macrophages in the context of the cellular micromilieu of classical Hodgkin lymphoma.
OBJECTIVE
Classical Hodgkin lymphoma (HL) consists of neoplastic Hodgkin and Reed-Sternberg cells (HRSC) and a nonneoplastic micromilieu that greatly outnumbers the HRSC. Studies on HRSC-related prognostic biomarkers have been unsuccessful, but the microenvironmental composition is of prognostic importance. Recently, the number of CD68-positive macrophages was correlated with adverse survival in HL, and there was a call to validate these results.


METHODS
We utilized immunohistochemistry to analyze the prognostic importance of the CD68-positive macrophage number compared to other cellular environmental components in an unselected series of 105 HLs in tissue microarrays.


RESULTS
Applying a cutoff score of >0.82% tumor macrophages, cases with increased numbers showed worse overall survival (mean 185 months, median 192) compared to cases with lower numbers (mean 285 months, median not reached). Eleven of 62 patients with ≤0.82% tumor macrophages died, compared to 19 of 43 with >0.82% (p < 0.001). The number of macrophages correlated with a low FOXP3-/high granzyme B-/high PD-1-positive micromilieu and patient age, but did not have independent prognostic significance. A combination background score taking into consideration all negative prognostic microenvironmental components (CD68-, PD-1- and granzyme B-positive cells) was of independent prognostic significance (p = 0.002).


CONCLUSIONS
Increased numbers of CD68-positive tumor macrophages indicate an adverse overall outcome in HL.
Department of Pathology, University of Basel, Basel, Switzerland. atzankov@uhbs.ch
Alexandar
A
Tzankov
Matthias S
MS
Matter
Stephan
S
Dirnhofer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism*; D002452:Cell Count; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D006689:Hodgkin Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000276:immunology*; D055815:Young Adult
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D051940:B7-2 Antigen; C497964:CD86 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C509213:GZMB protein, human; D053804:Granzymes