TY - JOUR
T1 - 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
T2 - a study by the Lunenburg Lymphoma Biomarker Consortium
AU - Stevens, Wendy B. C.
AU - Mendeville, Matias
AU - Redd, Robert
AU - Clear, Andrew J.
AU - Bladergroen, Reno
AU - Calaminici, Maria
AU - Rosenwald, Andreas
AU - Hoster, Eva
AU - Hiddemann, Wolfgang
AU - Gaulard, Philippe
AU - Xerri, Luc
AU - Salles, Gilles
AU - Klapper, Wolfram
AU - Phreundschuh, Michael
AU - Jack, Andrew
AU - Gascoyne, Randy D.
AU - Natkunam, Yasodha
AU - Advani, Ranjana
AU - Kimby, Eva
AU - Sander, Birgitta
AU - Sehn, Laurie
AU - Hagenbeek, Anton
AU - Raemaekers, John
AU - Gribben, John
AU - Kersten, Marie Jose'
AU - Ylstra, Bauke
AU - Weller, Edie
AU - de Jong, Daphne
AU - Pfreundschuh, Michael
PY - 2017/7/31
Y1 - 2017/7/31
N2 - 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. The criteria were: 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 rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP[-like]), while refuting the prognostic impact of various other markers
AB - 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. The criteria were: 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 rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP[-like]), while refuting the prognostic impact of various other markers
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85026732801&partnerID=8YFLogxK
U2 - https://doi.org/10.3324/haematol.2017.165415
DO - https://doi.org/10.3324/haematol.2017.165415
M3 - Article
C2 - 28411252
SN - 0390-6078
VL - 102
SP - 1413
EP - 1423
JO - Haematologica
JF - Haematologica
IS - 8
ER -