Figure 4.
CD70 overexpression in nodal MCLs. (A) Venn diagram showing the overlap between the NanoString-based statistically significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs (50 genes; blue circle) and SOX11+ compared with RLNs (54 genes; yellow circle). (B) Heatmap showing the scaled expression levels of common 24 significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs and RLNs. Red represents increased expression and green reduced expression. Genes with an adjusted P value (Q-value) < .15 were considered. (C) CD70 mRNA expression levels in unpurified lymph node MCL samples (unpurified LN; n = 34), CD19+ purified cells from LN samples (CD19+ LN; n = 4) and peripheral blood samples (CD19+ PB; n = 15) (GSE70910). *q value < .05, ***q value < .001. (D) Representative histological sections from (i) an RLN sample, (ii) SOX11+, and (iii) SOX11− nodal MCL biopsy, stained with specific anti-human CD70 antibody (×100). A double IHC staining with anti-human CD70 (brown) and (iv) anti-human cyclin D1 (red) antibodies (×100) was performed in the same SOX11− nodal MCL case as in (iii) to confirm the expression of CD70 by tumor cells (black arrows). Pictures contain insets with magnification (×400). (E) IHC quantifications of CD70+ cells in our series of SOX11+ (n = 51) and SOX11− (n = 13) nodal MCL primary samples. (F) IHC quantification of CD70 expression in nodal samples according to classic, blastoid/pleomorphic, or small cell MCL variants. (G) Positive correlation between CD70+ and Ki67+ cells, quantified by IHC in our series of nodal MCL. SOX11+ MCL are indicated in red, whereas SOX11− MCLs are in blue. Graphs show Pearson correlation coefficient (r), P value, and number of cases analyzed (N). (H) IHC quantification of CD70 expression in nodal MCL samples according to high (Ki67 >30%) and low (Ki67 ≤30%) proliferation rates in our series of SOX11+ (red) and SOX11− (blue) primary MCL cases. MCL cases diagnosed as blastoid/pleomorphic cytological variant are highlighted in green. The significance of differences was determined by independent samples Student t test: *P < .05, **P < .01, ***P < .001. (I) Kaplan-Meier curve and Cox regression showing the association of CD70+ cells, quantified by IHC using our series of SOX11+ nodal MCL primary samples (n = 40), with OS. (J) Kaplan-Meier curve and Cox regression showing the association of CD70 mRNA expression with OS, using previously published GEP from nodal samples and clinical data from 122 nodal SOX11+ MCL primary cases (GSE93291). High values were defined by Maxstat (cutoff point IHC = 25%, cutoff point mRNA = 9.9). Log-rank test P values, hazard ratios (HR) with 95% confidence interval (CI), and Cox regression P values are shown.

CD70 overexpression in nodal MCLs. (A) Venn diagram showing the overlap between the NanoString-based statistically significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs (50 genes; blue circle) and SOX11+ compared with RLNs (54 genes; yellow circle). (B) Heatmap showing the scaled expression levels of common 24 significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs and RLNs. Red represents increased expression and green reduced expression. Genes with an adjusted P value (Q-value) < .15 were considered. (C) CD70 mRNA expression levels in unpurified lymph node MCL samples (unpurified LN; n = 34), CD19+ purified cells from LN samples (CD19+ LN; n = 4) and peripheral blood samples (CD19+ PB; n = 15) (GSE70910). *q value < .05, ***q value < .001. (D) Representative histological sections from (i) an RLN sample, (ii) SOX11+, and (iii) SOX11− nodal MCL biopsy, stained with specific anti-human CD70 antibody (×100). A double IHC staining with anti-human CD70 (brown) and (iv) anti-human cyclin D1 (red) antibodies (×100) was performed in the same SOX11− nodal MCL case as in (iii) to confirm the expression of CD70 by tumor cells (black arrows). Pictures contain insets with magnification (×400). (E) IHC quantifications of CD70+ cells in our series of SOX11+ (n = 51) and SOX11− (n = 13) nodal MCL primary samples. (F) IHC quantification of CD70 expression in nodal samples according to classic, blastoid/pleomorphic, or small cell MCL variants. (G) Positive correlation between CD70+ and Ki67+ cells, quantified by IHC in our series of nodal MCL. SOX11+ MCL are indicated in red, whereas SOX11− MCLs are in blue. Graphs show Pearson correlation coefficient (r), P value, and number of cases analyzed (N). (H) IHC quantification of CD70 expression in nodal MCL samples according to high (Ki67 >30%) and low (Ki67 ≤30%) proliferation rates in our series of SOX11+ (red) and SOX11− (blue) primary MCL cases. MCL cases diagnosed as blastoid/pleomorphic cytological variant are highlighted in green. The significance of differences was determined by independent samples Student t test: *P < .05, **P < .01, ***P < .001. (I) Kaplan-Meier curve and Cox regression showing the association of CD70+ cells, quantified by IHC using our series of SOX11+ nodal MCL primary samples (n = 40), with OS. (J) Kaplan-Meier curve and Cox regression showing the association of CD70 mRNA expression with OS, using previously published GEP from nodal samples and clinical data from 122 nodal SOX11+ MCL primary cases (GSE93291). High values were defined by Maxstat (cutoff point IHC = 25%, cutoff point mRNA = 9.9). Log-rank test P values, hazard ratios (HR) with 95% confidence interval (CI), and Cox regression P values are shown.

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