CD30 and prognosis
Very little is known about the prognostic implications of the incidence or intensity of CD30 expression. Outcomes are poor for many of the tumors described in the Science of CD30 project, with median survival under 1 year.1,2,3,4 In some malignancies, the limited data suggest no association between CD30 expression and prognosis,1,5 though no large-scale analyses have been conducted and the association has not been investigated in most tumor types. A great deal of research remains to be done in this area, though the rarity of most of these tumors makes it difficult to conduct large studies. This section will present the limited evidence available on the effect of CD30 expression on outcome.
Adult T-cell leukemia/lymphoma
In a single-center study, the clinical course of 7 patients with CD30-positive ATLL was similar to that of 29 patients with CD30-negative ATLL, with a mean OS of about 10 months.4 More data are needed to confirm these results.
Diffuse large B-cell lymphoma
The clinical course of DLBCL is highly variable, but this is a potentially curable malignancy.6,7 Limited data (n = 11) from the European Organisation for Research and Treatment of Cancer (EORTC) suggest that CD30-positive disease is associated with improved overall and progression-free survival vs DLBCL of unspecified immunotype (figure).8 In contrast, an earlier study by Noorduyn et al failed to demonstrate any correlation between CD30 expression and survival in 80 large B-cell lymphomas, 25 with strong CD30 expression (mostly >80% of cells positive), 30 with partial CD30 expression (generally <20% of cells positive) and 25 with no CD30 expression.9
Expression of CD30 in DLBCL increases failure-free survival8
DLBCL: n = 11; unspecified DLBCL: n = 103
Enteropathy-associated T-cell lymphoma
In an international study with 62 patients, CD30 expression did not appear to affect survival. The median OS was only 10 months, with no significant difference by immunophenotype.1
Extranodal NK/T-cell lymphoma, nasal type
The prognosis for ENKTL is the worst among all of the PTCL categories, with a median OS of only 7.8 months.2 Kuo et al suggest there is no significant difference in survival between CD30-positive and CD30-negative disease, though their analysis involved a very small number of patients (N = 22) and requires confirmation in a larger population.5
The effect of CD30 expression on tumor behavior, growth and response to therapy has not been well investigated in FL. A recent study suggests that CD30 expression may be a negative prognostic indicator in this malignancy. In an analysis of 186 cases of nodal FL, CD30 expression was associated with a significantly shorter OS. CD30 expression ranged from 0%-25%, with a mean expression of 0.5%. In a univariate analysis, the estimated relative risk of death associated with CD30 expression was 2.3942 (95% CI: 1.3125-4.3672, P = .0044).10
MF generally has an indolent course (figure), but data suggest that survival is shorter if dermal cells are highly CD30-positive (greater than the median). In the 47 patients studied by Edinger et al, higher percentages of CD30-positive dermal cells (>4.7%) were associated with a higher Bunn-Lamberg stage at diagnosis, a higher maximum stage and poorer survival.11
Increased expression of CD30 on dermal cells significantly reduces survival in mycosis fungoides11
Transformation shortens OS, with a median OS of 3.1 years vs 13.6 years in a nontransformed group (P = .0029).12 In a small series (n = 22), patients with CD30-positive transformation tended toward a better outcome than patients with CD30-negative transformation (P = .19).13 This finding was supported by Barberio et al in a study of 17 cases of transformed MF: here also CD30 expression appeared to be linked to better prognosis. Median survival was longer for the 9 patients with CD30-positive disease than for the 8 patients with CD30-negative disease, with survival linked to the intensity of CD30 expression. Median survival was 60 months for those cases in which ≥75% of cells expressed CD30 (n = 4), 28 months when <75% of cells expressed CD30 (n = 5) and only 21.1 months when the transformed cells were CD30-negative (n = 8). Interestingly, the 4 patients with high expression (>75%) of CD30 in transformed cells achieved complete remission after first-line treatment, while the four deaths seen on study were in CD30-negative cases.14
Peripheral T-cell lymphoma, not otherwise specified
PTCL-NOS is one of the few malignancies in which expression of CD30 may be correlated with prognosis. Expression of CD30 in ≥80% of cells has been associated with an extremely poor prognosis: 5-year failure-free survival (FFS) of 9% (figure) and 5-year overall survival (OS) of only 19%. In this study, 5-year FFS was 20% and 5-year OS was 32% for the population with PTCL-NOS when immunophenotype was not considered.15
PTCL-NOS: n = 331; PTCL-NOS ≥80% CD30+: n = 15
Primary cutaneous anaplastic large cell lymphoma
Limited data suggest that primary CTCLs that express CD30 have a better prognosis than primary CTCLs that are CD30-negative, irrespective of histologic subtype.16 This is consistent with the 5-year OS of 90% seen in primary cALCL, which is strongly positive for CD30. This study by the International Peripheral T-Cell Lymphoma Project involved 22 cases of primary cALCL. In all cases, ≥80% of tumor cells expressed CD30.15
- Delabie J, Holte H, Vose JM, et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project. Blood. 2011;118(1):148-155.
- Au W-Y, Weisenburger DD, Intragumtornchai T, et al; International Peripheral T-Cell Lymphoma Project. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood. 2009;113(17):3931-3937.
- Higuchi M, Matsuda T, Mori N, et al. Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation. Retrovirology. 2005;2:29-40.
- Ohtsuka E, Kikuchi H, Nasu M, Takita-Sonoda Y, Fujii H, Yokoyama S. Clinicopathological features of adult T-cell leukemia with CD30 antigen expression. Leuk Lymphoma. 1994;15(3-4):303-310.
- Kuo T-T, Shih L-Y, Tsang N-M. Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities. Int J Surg Pathol. 2004;12(4):375-387.
- Armitage JO, Weisenburger DD; Non-Hodgkin's Lymphoma Classification Project. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. J Clin Oncol. 1998;16(8):2780-2795.
- Eow GI, Kim LH, Peh SC. The pattern of CD15, CD30 and Bcl-2 expression in diffuse large B-cell lymphoma. Med J Malaysia. 2006;61(4):416-421.
- Maes B, Anastasopoulou A, Kluin-Nelemans JC, et al; EORTC Lymphoma Group. Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+ anaplastic B-cell subtypes exhibit distinct clinical features. Ann Oncol. 2001;12(6):853-858.
- Noorduyn LA, de Bruin PC, van Heerde P, van de Sandt MM, Ossenkoppele GJ, Meijer CJLM. Relation of CD30 expression to survival and morphology in large cell B cell lymphomas. J Clin Pathol. 1994;47(1):33-37.
- Camacho FI, Bellas C, Corbacho C, et al. Improved demonstration of immunohistochemical prognostic markers for survival in follicular lymphoma cells. Mod Pathol. 2011;24(5):698-707.
- Edinger JT, Clark BZ, Pucevich BE, Geskin LJ, Swerdlow SH. CD30 expression and proliferative fraction in nontransformed mycosis fungoides. Am J Surg Pathol. 2009;33(12):1860-1868.
- Diamandidou E, Colome-Grimmer M, Fayad L, Duvic M, Kurzrock R. Transformation of mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis. Blood. 1998;92(4):1150-1159.
- Arulogun SO, Prince HM, Ng J, et al. Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood. 2008;112(8):3082-3087.
- Barberio E, Thomas L, Skowron F, Balme B, Dalle S. Transformed mycosis fungoides: clinicopathological features and outcome. Br J Dermatol. 2007;157(2):284-289.
- Savage KJ, Harris NL, Vose JM, et al; International Peripheral T-Cell Lymphoma Project. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 2008;111(12):5496-5504.
- Beljaards RC, Meijer CJLM, Scheffer E, et al. Prognostic significance of CD30 (Ki-1/Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin: a clinicopathologic and immunohistochemical study in 20 patients. Am J Pathol. 1989;135(6):1169-1178.