Macrophage-Derived Chemokine Expression in Classical Hodgkin's Lymphoma: Application of Tissue Microarrays

Hedvat, Cyrus V.; Jaffe, Elaine S.; Qin, Jing; Filippa, Daniel A.; Cordon‐Cardo, Carlos; Tosato, Giovanna; Nimer, Stephen D.; Teruya‐Feldstein, Julie

doi:10.1038/modpathol.3880473

Cited by 49 publications

(35 citation statements)

References 21 publications

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“…49 By IHC, 87% of cHL cases demonstrated MDC expression, primarily localized to RS cells. 55 Eotaxin expression is higher in cHL tissues than in normal lymphoid tissues, as demonstrated by RT-PCR. 49 Within cHL subtypes, elevated eotaxin expression was preferentially associated with NSHL cases.…”

Section: Th2 Chemokinesmentioning

confidence: 75%

The role of cytokines in classical Hodgkin lymphoma

Skinnider

Mak

2002

Blood

462

370

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IntroductionClassical Hodgkin lymphoma (cHL) is a lymphoid malignancy with characteristic features that distinguish it from nodular lymphocyte-predominant HL (NLPHL) and non-Hodgkin lymphomas (NHLs). 1,2 The malignant cells in cHL, termed the Reed-Sternberg (RS) cells, constitute only a minor component of the tumor, whereas the majority of the malignancy is composed of a mixed inflammatory infiltrate variably composed of lymphocytes, eosinophils, fibroblasts, macrophages, and plasma cells. Patients with cHL also commonly present with constitutional symptoms such as fever, weight loss, and night sweats, and an apparent systemic defect in cell-mediated immune responses. Many of these distinctive clinical and histopathologic features of cHL reflect an abnormal immune response thought to be due largely to the effects of a wide variety of cytokines and chemokines that are primarily produced by the RS cells, but also secondarily by the surrounding reactive infiltrate. This review summarizes the data on cytokine production in cHL, examines cytokine signaling, and discusses the role of cytokines in the clinical and pathologic features of this disease.Classical HL is now considered a distinct clinicopathologic entity from NLPHL and can be divided into 4 morphologic subtypes: nodular sclerosis cHL (NSHL), mixed cellularity cHL (MCHL), lymphocyte-rich cHL (LRCHL), and lymphocytedepleted cHL (LDHL). 2 There are few data on cytokine involvement in LRCHL and LDHL, because each disease comprises less than 5% of all cHL cases. As a result, nearly all of the data on the role of cytokines in cHL are derived from the study of NSHL and MCHL cases.Cytokines are low-molecular-weight proteins with a wide variety of functions. They not only regulate immune and inflammatory responses but also contribute to hematopoiesis, wound healing, and other biologic processes. Cytokines are extremely potent molecules active in nanomolar to picomolar concentrations. Typically, a cytokine either acts in a paracrine manner to modulate the activity of surrounding cells, or in an autocrine fashion to affect the cell that produced it. In the context of cHL, cytokines produced by RS cells are thought to contribute to the pathogenesis of this disease both by acting as autocrine growth factors and by initiating and sustaining the reactive infiltrate. Alternatively, cytokines produced by surrounding reactive cells may be contributing to RS cell proliferation and survival.The expression and activity of cytokines in cHL can be studied using cell lines derived from RS cells and in primary cHL tissues. Each approach has its limitations, so that a combination of both strategies provides the most comprehensive information on the activity of a specific cytokine. Cell lines derived from RS cells have been extremely useful in the study of cHL. 3,4 However, outgrowth of such a cell line from cHL patient tissues is extremely rare, so that the few cell lines available may not represent the full spectrum of clinical and pathologic features of this disease. The RS cell li...

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Section: Th2 Chemokinesmentioning

confidence: 75%

The role of cytokines in classical Hodgkin lymphoma

Skinnider

Mak

2002

Blood

462

370

View full text Add to dashboard Cite

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“…Different groups in several types of human tumors have previously demonstrated the suitability of this technique. To our knowledge, a single limited study 24 has previously provided evidence of the feasibility of this tool in HL, based solely on the expression of a single protein.…”

Section: Discussionmentioning

confidence: 99%

“…However, the feasibility of this technique for analyzing highly heterogeneous tumors such as HL remains to be elucidated. Recent studies using TMA 24 have shown the potential of this technology for restricted analyses in HL.…”

Section: Introductionmentioning

confidence: 99%

Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Garcı́a

Camacho²,

Morente³

et al. 2002

Blood

219

184

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“…Core needle biopsies of pre-existing paraffin-embedded tissue were obtained and then re-embedded in an arrayed master block using techniques originally developed by Kononen et al 10 and then modified by Hedvat et al 11 We used the Beecher Instruments (Sun Prairie, WI, USA) arraying device to produce sample circular spots that were 0.6 mm in diameter. Three core needle specimens were obtained from each tumor and companion tissue specimen.…”

Section: Tumor Microarraysmentioning

confidence: 99%

Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis

et al. 2006

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Many endometrial adenocarcinomas, particularly those of endometrioid type, express estrogen receptors (ERs), progesterone receptors (PRs), and vimentin. This typical immunophenotype is frequently considered a standard against which others are compared when immunohistochemistry is used for differential diagnosis. We tested large numbers of endometrial cancers, enriched for high-grade tumors, to determine whether this reported immunophenotype was valid and whether expression differences between types of endometrial carcinoma could be exploited for diagnostic purposes. Immunohistochemical stains were performed on the following types of endometrial cancers using established methodology: International Federation of Gynecology and Obstetrics (FIGO) grades 1 and 2 endometrioid-42; FIGO grade 3 endometrioid-40; serous-24; clear cell-11; carcinosarcoma-9. In total, 92% of serous carcinomas expressed p16 strongly compared to weak-tomoderate expression of p16 in 7-67% of other tumors (FIGO grades 1 and 2 carcinoma and carcinosarcoma, respectively). A total of 84% of FIGO grades 1 and 2 carcinomas expressed ER compared to 9-54% of other tumors (clear cell and serous carcinomas respectively); 83% of FIGO grades 1 and 2 expressed PR compared to 11-54% of other carcinomas (carcinosarcoma and serous carcinoma, respectively). Most carcinomas were negative for monoclonal carcinoembryonic antigen (mCEA), and those that were positive showed mostly only focal membrane expression. Vimentin was expressed in nearly every tumor. Most tumors were diffusely vimentin positive, but a large range of expression patterns, from focal to diffuse and from weak to strong, was noted. Only 70% of FIGO grades 1 and 2 endometrioid carcinomas and 26% of grade 3 endometrioid carcinomas possessed the reportedly characteristic endometrial cancer immunophenotype p16 (À), ER ( þ ), PR ( þ ), mCEA (À), and vimentin ( þ ). Endometrial cancers demonstrate substantial immunophenotypic diversity that remained apparent even within groups of similar histologic subtype and grade. ER, PR, and p16 expression was more illustrative of tumor type and degree of differentiation than they were of endometrial origin. In contrast, the vimentin-positive/CEA-negative phenotype remained the most constant among all endometrial cancers.

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Macrophage-Derived Chemokine Expression in Classical Hodgkin's Lymphoma: Application of Tissue Microarrays

Cited by 49 publications

References 21 publications

The role of cytokines in classical Hodgkin lymphoma

The role of cytokines in classical Hodgkin lymphoma

Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis

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