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Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: A study by the Lunenburg Lymphoma Biomarker Consortium.

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: A study by the Lunenburg Lymphoma Biomarker Consortium.
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Stevens WBC, Mendeville M, Redd R, Clear AJ, Bladergroen R, Calaminici M, Rosenwald A, Hoster E, Hiddemann W, Gaulard P, Xerri L, Salles G, Klapper W, Phreundschuh M, Jack A, Gascoyne RD, Natkunam Y, Advani R, Kimby E, Sander B, Sehn L, Hagenbeek A, Raemaekers J, Gribben J, Kersten MJ, Ylstra B, Weller E, de Jong D,


Stevens WBC, Mendeville M, Redd R, Clear AJ, Bladergroen R, Calaminici M, Rosenwald A, Hoster E, Hiddemann W, Gaulard P, Xerri L, Salles G, Klapper W, Phreundschuh M, Jack A, Gascoyne RD, Natkunam Y, Advani R, Kimby E, Sander B, Sehn L, Hagenbeek A, Raemaekers J, Gribben J, Kersten MJ, Ylstra B, Weller E, de Jong D, (click to view)

Stevens WBC, Mendeville M, Redd R, Clear AJ, Bladergroen R, Calaminici M, Rosenwald A, Hoster E, Hiddemann W, Gaulard P, Xerri L, Salles G, Klapper W, Phreundschuh M, Jack A, Gascoyne RD, Natkunam Y, Advani R, Kimby E, Sander B, Sehn L, Hagenbeek A, Raemaekers J, Gribben J, Kersten MJ, Ylstra B, Weller E, de Jong D,

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Haematologica 2017 04 14() pii haematol.2017.165415
Abstract

In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries; early failure: progression or lymphoma-related death <2 years versus long remission: response duration of >5 years. Immunohistochemical staining for T-cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type (p=0.006), gain of chromosome 18 (p=0.002), low percentages of CD8+ cells (p=0.011) and CD163+ areas (p=0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with R-CHOP (like), while refuting the prognostic impact of various other markers.

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