Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Samples
2.2. Immunohistochemical Staining for RHAMM and CD44
2.3. Digital Image Analysis
2.4. Statistical Analysis
3. Results
3.1. RHAMM but Not CD44 Expression Predicts HT in Follicular Lymphoma
3.2. The Relationship between CD44 and RHAMM Expression Predicts HT in FL
3.3. High Tumor-Tissue Expression of RHAMM and Low Intrafollicular CD44 Expression Predicts Shorter Transformation-Free Survival
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | All n = 65 n (%) | nt-FL n = 34 n (%) | st-FL n = 31 n (%) | p-Value |
---|---|---|---|---|
Sex | NS | |||
Male | 34 (52) | 16 (47) | 18 (42) | |
Female | 31 (48) | 18 (53) | 13 (58) | |
Age at FL diagnosis | NS | |||
Median | 55 | 54 | 57 | |
Range | 35–78 | 35–76 | 40–78 | |
Ann Arbor stage | <0.001 | |||
I–II | 17 (26) | 15 (44) | 2 (6) | |
III–IV | 46 (71) | 18 (53) | 28 (90) | |
Unknown | 2 (3) | 1 (3) | 1 (3) | |
FLIPI | <0.001 | |||
Low | 24 (37) | 20 (59) | 4 (13) | |
Intermediate | 18 (28) | 10 (29) | 8 (26) | |
High | 19 (29) | 2 (6) | 17 (55) | |
Unknown | 4 (6) | 2 (6) | 2 (6) | |
LDH-elevation | 0.022 | |||
Yes | 8 (12) | 1 (3) | 7 (23) | |
No | 53 (82) | 31 (91) | 22 (71) | |
Unknown | 4 (6) | 2 (6) | 2 (6) | |
B-symptoms | NS | |||
Yes | 15 (23) | 6 (18) | 9 (29) | |
No | 47 (72) | 27 (79) | 20 (65) | |
Unknown | 4 (6) | 1 (3) | 2 (6) | |
Performance score | NS | |||
<2 | 49 (75) | 28 (82) | 21 (68) | |
≥2 | 13 (20) | 5 (15) | 8 (26) | |
Unknown | 3 (5) | 1 (3) | 2 (6) | |
Bone marrow Involvement | 0.018 | |||
Yes | 20 (31) | 6 (18) | 14 (45) | |
No | 36 (55) | 24 (71) | 12 (39) | |
Unknown | 9 (14) | 4 (12) | 5 (16) | |
Anemia | NS | |||
Yes | 5 (8) | 1 (3) | 4 (13) | |
No | 57 (88) | 32 (94) | 25 (81) | |
Unknown | 3 (5) | 1 (3) | 2 (6) | |
FL histology | NS | |||
FL grade 1–2 | 56 (86) | 29 (85) | 27 (87) | |
FL grade 3A | 9 (14) | 5 (15) | 4 (13) | |
RHAMM expression, biopsy | 0.019 | |||
Low | 34 (52) | 23 (68) | 11 (35) | |
High | 31 (48) | 11 (32) | 20 (65) | |
CD44 expression, biopsy | NS | |||
Low | 26 (40) | 14 (41) | 12 (39) | |
High | 39 (60) | 20 (59) | 19 (61) | |
Ratio CD44/RHAMM expression, biopsy | 0.072 | |||
Low | 42 (65) | 18 (53) | 24 (77) | |
High | 23 (35) | 16 (47) | 7 (23) | |
RHAMM expression, intrafollicular * | NS | |||
Low | 42 (71) | 23 (70) | 19 (73) | |
High | 17 (29) | 10 (30) | 7 (27) | |
CD44 expression, intrafollicular * | NS | |||
Low | 26 (44) | 12 (36) | 14 (54) | |
High | 33 (56) | 21 (67) | 12 (46) | |
Ratio CD44/RHAMM expression, intrafollicular * | 0.083 | |||
Low | 37 (63) | 17 (52) | 20 (77) | |
High | 22 (37) | 16 (48) | 6 (23) | |
Initial treatment | NA | |||
Alkylator-based | 22 (34) | 8 (24) | 14 (45) | |
Antracyclin-based | 21 (32) | 12 (35) | 9 (29) | |
Rituximab | 19 (29) | 6 (18) | 13 (42) | |
Observation only | 4 (6) | 3 (9) | 1 (3) | |
R-Chemotherapy | 9 (14) | 1 (3) | 8 (28) | |
Other | 5 (8) | 2 (6) | 3 (10) | |
Unknown | 19 (29) | 11 (32) | 8 (26) |
Clinicopathological Feature | Univariate p and HR (95% CI) Values | Multivariate p and HR (95% CI) Values | ||||||
---|---|---|---|---|---|---|---|---|
OS | PFS | OS | PFS | |||||
Sex, male | NS | 0.9 (0.5–1.8) | NS | 1.0 (0.6–1.7) | NS | 1.3 (0.6–3.0) | NS | 1.3 (0.7–2.4) |
Age above 60 | NS | 1.7 (0.8–3.3) | NS | 1.7 (0.9–3.0) | NS | 1.6 (0.6–3.9) | NS | 1.3 (0.6–2.7) |
Ann Arbor stage III–IV | 0.016 | 1.6 (1.1–2.2) | 0.005 | 1.4 (1.1–1.8) | NS | 1.5 (0.9–2.5) | 0.021 | 1.5 (1.1–2.1) |
High FLIPI risk score | 0.009 | 2.9 (1.3–6.3) | 0.006 | 2.6 (1.3–5.3) | NS | 1.8 (0.7–4.5) | 0.058 | 2.3 (0.9–5.5) |
Elevated LDH | 0.033 | 2.9 (1.1–7.6) | 0.004 | 3.4 (1.5–7.7) | 0.056 | 3.2 (0.9–10.3) | 0.006 | 3.9 (1.5–10.5) |
B-symptoms | NS | 1.5 (0.7–3.3) | NS | 1.5 (0.8–2.8) | NS | 1.1 (0.4–2.8) | NS | 1.0 (0.5–2.2) |
Performance score ≥ 2 | NS | 2.0 (0.9–4.3) | NS | 1.4 (0.7–2.6) | NS | 2.0 (0.8–5.3) | NS | 1.6 (0.7–3.4) |
Anemia | NS | 1.6 (0.5–5.3) | NS | 1.5 (0.5–4.3) | NS | 0.7 (0.2–2.7) | NS | 0.7 (0.2–2.2) |
Bone marrow involvement | NS | 1.9 (0.9–4.2) | 0.043 | 1.9 (1.0–3.4) | NS | 1.0 (0.4–2.6) | NS | 0.9 (0.4–1.9) |
FL grade 3A | NS | 0.9 (0.3–2.7) | NS | 1.1 (0.5–2.6) | NS | 1.3 (0.4–4.7) | NS | 1.4 (0.5–4.1) |
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Enemark, M.B.; Hybel, T.E.; Madsen, C.; Lauridsen, K.L.; Honoré, B.; Plesner, T.L.; Hamilton-Dutoit, S.; d’Amore, F.; Ludvigsen, M. Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients. Cancers 2022, 14, 1316. https://doi.org/10.3390/cancers14051316
Enemark MB, Hybel TE, Madsen C, Lauridsen KL, Honoré B, Plesner TL, Hamilton-Dutoit S, d’Amore F, Ludvigsen M. Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients. Cancers. 2022; 14(5):1316. https://doi.org/10.3390/cancers14051316
Chicago/Turabian StyleEnemark, Marie Beck, Trine Engelbrecht Hybel, Charlotte Madsen, Kristina Lystlund Lauridsen, Bent Honoré, Trine Lindhardt Plesner, Stephen Hamilton-Dutoit, Francesco d’Amore, and Maja Ludvigsen. 2022. "Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients" Cancers 14, no. 5: 1316. https://doi.org/10.3390/cancers14051316