CD 138, syndecan I
The syndecans are a family of four transmembrane glycoproteins. Syndecans 1 and 2 appear to be altenatively expressed: syndecan 1 is the major syndecan in epithelial cells while syndecan 2 is more abundantly expressed in mesothelium and mesenchymal cells10.
Syndecan 1, CD138, is a 220 kd sulphate-rich proteoglycan adhesion molecule expressed in the late stages of B-cell differentiation, acquired as they differentiate towards plasma cells. Syndecan is up-regulated by WT-1 and in turn acts as a receptor for collagen, fibronectin and thrombospondin3. It binds basic fibroblast growth factor, an angiogenic agent, and thereby modulates neovascularisation6. The free ectodomain of syndecan I suppresses proliferation of tumour cells6.
Immunohistochemical expression
Antigen retrieval is required for formalin-fixed tissue and enhances staining of B-5 fixed tissue4.
-
non-neoplastic plasma cells4
-
squamous epithelium of tonsils, skin and adnexa, prostatic glands and Hassall corpuscles4.
-
Leydig cells1
-
Neuronal cells1
-
Endothelial and stromal cells during wound healing1
-
other components of bone marrow and lymph nodes - lymphocytes, dendritic and reticulum cells, endothelial cell, myeloid cells, erythroblasts and megakaryocytes are NEGATIVE1.
-
myeloma1,4 Reactivity appears to be rapidly lost in unfixed cells subject to flow cytometry1.
-
Reed-Sternberg cells1
-
immunoblastic lymphoma with plasmacytoid differentiation: 5/13 cases1
|
|
Haematolymphoid disorders
|
CD138
|
|
|
Multiple myeloma
|
8/81,
43/43(in bone marrow biopsy: strong positivity with membrane accentuation in all cases)4,
2/16(both positive cases had plasmacytoid morphological features)4,
1/1(strong positivity)9
|
|
Plasmacytoid lymphoma
|
2/21,
|
|
Lymphoplasmacytic lymphoma
|
9/9(positivity restricted to mature plasma cells)1,
4/4(reactivity restricted to plasma cell component)4,
3/3(strong positivity)9
|
|
Acute lymphoblastic leukaemia
|
0/3(in bone marrow biopsy)4
|
|
Acute myelogenous leukaemia
|
0/13(in bone marrow biopsy)4
|
|
Chronic myelogenous leukaemia
|
0/2(in bone marrow biopsy)4
|
|
CLL/small lymphocytic lymphoma
|
0/201,
0/5(in bone marrow biopsy)4, 0/144,
11/11(B-CLL, strong positivity after antigen retrieval at high temperature in a pressure cooker using citrate solution)9
|
|
Follicular lymphoma
|
0/181,
0/2(in bone marrow biopsy)4, 0/44,
0/14(on tissue microarray)4, 0/79
|
|
Marginal zone lymphoma
|
0/31,
4/6(3/3 extranodal and 1/1 nodal showed strong positivity for the extensive clonal plasmacytic component. 2 splenic cases were negative)4, 0/69
|
|
Mantle cell lymphoma
|
0/121,
0/1(in bone marrow biopsy)4, 0/44, 0/99
|
|
Hairy cell leukaemia
|
0/2(in bone marrow biopsy)4
|
|
DLBCL
|
5/35(positivity restricted to immunoblastic lymphomas with plasmacytoid features)1,
0/1(in bone marrow biopsy)4,
2/16(positivity restricted to the only two cases with plasmacytoid features)4,
1/44(on tissue microarray positivity restricted to the one case with plasmacytoid features)4, 1/147, 0/22, 0/59
|
|
Mediastinal large B-cell lymphoma
|
0/14, 0/19
|
|
Burkitt's lymphoma
|
0/71,
0/1(in bone marrow biopsy)4, 0/12, 0/39
|
|
B-cell Lymphoma NOS
|
0/39
|
|
Precursor T-lymphoblastic lymphoma
|
0/29
|
|
Peripheral T-cell lymphoma
|
0/151,
0/1(in bone marrow biopsy)4, 0/14, 0/19
|
|
Mycosis fungoides
|
0/44
|
|
Angioimmunoblastic lymphoma
|
0/19
|
|
T-cell Lymphoma NOS
|
0/19
|
|
Anaplastic large cell lymphoma
|
0/51, 0/34, 0/39
|
|
Mycosis fungoides
|
0/71
|
|
Post transplant lymphoproliferative disease
|
0/24
|
|
Nodular lymphocyte predominant Hodgkin disease
|
0/61, 0/34,
0/2(on tissue microarray)4
|
|
Classical Hodgkin disease
|
23/311,
0/16(in 11 cases, the fibroblasts and collagen bands stained)4
|
|
Mast cell disease
|
0/1(in bone marrow biopsy)4
|
|
Langerhans cell histiocytosis
|
0/14
|
|
Non-neoplastic disease
|
0/3(in bone marrow biopsy: erythroid hyperplasia, myeloid hyperplasia and a remission marrow following AML)4,
0/14(5 reactive lymphadenopathy, 2 HIV-related lymphadenopathy, 1 CMV lymphadenitis, 1 dermatopathic lymphadenitis, 1 granulomatous lymphadenitis, 1 infectious mononucleosis, 1 Rosai-Dorfmann disease [ delicate stromal positivity], 1 Castleman disease [delicate stromal positivity] and 1 Kikuchi's disease)4
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
Non-haematolymphoid disorders
|
CD138
|
|
| |
Reactive mesothelial proliferation
|
0/11(5 pleural, 2 peritoneal, 1 pericardial effusions and 3 peritoneal washings)2
|
| |
Malignant mesothelioma
|
2/24(in two cases, staining was moderate or strong but of <5% of cells)2, 1/213,
2/2(focal weak staining)4,
52/57(using frozen sections: sarcomatoid mesotheliomas showed weaker staining than did epithelial or biphasic cases)6
|
| |
Metastatic carcinoma, overall
|
32/58(most cases showed strong staining, of a variable percentage of cells)2
|
| |
Lung
|
adenocarcinoma
|
8/122, 11/213
|
| |
squamous cell carcinoma
|
4/42, 1/12
|
| |
non-small cell carcinoma. NOS
|
5/5(4 primary, 1 metastatic: membranous and granular cytoplasmic staining in one case: all also showed stromal staining)4
|
| |
small cell carcinoma
|
2/22, 1/12, 0/63,
1/2(metastases: positivity in viable and necrotic cells: 2 cases also showed stromal staining)4
|
| |
sarcomatoid carcinoma
|
1/12
|
| |
poorly differentiated with neuroendocrine features
|
0/12
|
| |
carcinomas overall
|
11/162, 11/273
|
| |
pleuropulmonary blastoma
|
0/12
|
| |
Ovary
|
papillary serous
|
8/152
|
| |
endometrioid
|
1/12
|
| |
clear cell
|
1/12
|
| |
mixed Mullerian tumour
|
012
|
| |
poorly differentiated carcinoma
|
1/12
|
| |
overall
|
8/112, 10/243
|
| |
Skin
|
squamous cell carcinoma
|
25/253
|
| |
basal cell carcinoma
|
14/203
|
| |
Merkel cell carcinoma
|
2/93
|
| |
Thyroid
|
follicular adenoma
|
10/243
|
| |
papillary carcinoma
|
2/93, 1/14
|
| |
medullary carcinoma
|
2/173, 2/24
|
| |
Salivary gland tumour
|
various
|
3/113
|
| |
myoepithelioma
|
1/1with marked plasmacytoid morphology: diffuse strong membranous positivity)4
|
| |
Larynx
|
squamous cell carcinoma
|
3/32,
|
| |
Breast
|
ductal and lobular carcinomas
|
4/42, 2/62, 18/263,
4/6(in bone marrow biopsy: in some cases, the morphology of the tumour cells could be confused with plasma cells)4,
8/9(7 cases also showed stromal staining)4
|
| |
Pancreas
|
adenocarcinoma
|
1/32, 4/133
|
| |
Colon
|
adenocarcinoma
|
5/51, 0/32, 9/103,
3/3(1 case also showed stromal staining)4
|
| |
Uterus
|
endometrioid adenocarcinoma
|
2/32, 9/103
|
| |
Oesophagus
|
adenocarcinoma
|
2/22,
0/1(in bone marrow biopsy)4
|
| |
Kidney
|
renal cell carcinoma
|
12/193,
1/1(metastatic: focal weak staining)4
|
| |
Bladder
|
transitional cell carcinoma
|
1/22, 22/243, 3/34
|
| |
Prostate
|
adenocarcinoma
|
1/22, 6/183,
1/1(in bone marrow biopsy)4
|
| |
Stomach
|
adenocarcinoma
|
0/12, 2/153,
4/5(metastases: positivity in viable and necrotic cells: one case also showed stromal staining)4
|
| |
Liver
|
hepatocellular carcinoma
|
15/253, 2/24
|
| |
cholangiocarcinoma
|
1/12, 13/143
|
| |
embryonal sarcoma
|
0/12
|
| |
Adrenal
|
cortical tumour
|
7/203
|
| |
Phaeochromocytoma
|
0/24
|
| |
Thymoma
|
0/83,
1/1(showed both tumour cell and stromal staining)4
|
| |
Germ cell tumour, NOS
|
0/143
|
| |
Seminoma
|
0/14
|
| |
Schwannoma
|
0/14
|
| |
GIST
|
1/1(weak focal staining)4
|
| |
Leiomyosarcoma
|
1/2(metastatic)4
|
| |
Abdominal angiosarcoma
|
0/12
|
| |
Synovial sarcoma
|
2/2(a biphasic case showed strong membranous staining in the epithelial component and membranous and cytoplasmic staining of the spindle cell component. A monophasic case showed membranous and cytoplasmic staining)4
|
| |
Epithelioid sarcoma
|
0/103
|
| |
Neuroendocrine carcinoma
|
3/93,
0/1(in bone marrow biopsy)4
|
| |
Carcinoid tumour
|
3/32, 2/103
|
| |
|
|
| |
Malignant melanoma
|
1/12,
0/1(metastatic melanoma)2, 1/203,
5/10(moderate to strong membranous staining)4
|
| |
|
|
|
| |
|
|
|
| |
|
|
|
| |
Notes:
|
any degree of membrane staining was considered positive2
|
Loss of CD138 immunoreactivity in carcinomas may be associated with dedifferentiation9 or tumour progression.
Adenocarcinomas and mesotheliomas may show differences in the relative expression of syndecans 1 and 210:
| |
Reference 10
|
Adenocarcinoma
|
Mesothelioma
|
|
|
Syndecan 1 > syndecan 2
|
8
|
0
|
|
Syndecan 1 = syndecan 2
|
0
|
0
|
|
Syndecan 1 < syndecan 2
|
2(both these adenocarcinomas were poorly differentiated)
|
8
|
Diagnostic utility
Note that a number of non-haematolymphoid neoplasms (myoepithelioma, medullary carcinoma of thyroid, melanoma) may have a plasmacytoid morphology and may also be positive for CD138: an appropriate panel of antibodies needs to be sued.
-
Identifying and quantifying plasma cells in bone marrow samples1.
-
In mature B-cell neoplasms, immunoreactivity indicates plasma cell and/or postfollicular differentiation.
-
Possibly in the differentiation of adenocarcinoma (positive in 55% of cases) from mesothelioma (usually negative) but the data currently available is inadequate.
References
1 Costes V, Magen V, Legouffe E et al. The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens. Human Pathology 1999;30:1405-11. xxxxxxxxxx
2 Saqi A, Yun SS, Yu GH, et al. Utility of CD138 (syndecan-1) in distinguishing carcinomas from mesotheliomas. Diagn Cytopathol 2005; 33:65-70
3 Chu PG, Arber DA,Weiss LM. Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases. Am J Clin Pathol 2003; 120:64-70
4 O'Connell FP, Pinkus JL,Pinkus GS. CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol 2004; 121:254-63
5 Shah L, Walter KL, Borczuk AC, et al. Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with nonsmall cell lung carcinoma. Cancer 2004; 101:1632-8
6 Kumar-Singh S, Jacobs W, Dhaene K, et al. Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome. J Pathol 1998; 186:300-5
7 Chilosi M, Adami F, Lestani M, et al. CD138/syndecan-1: a useful immunohistochemical marker of normal and neoplastic plasma cells on routine trephine bone marrow biopsies. Mod Pathol 1999; 12:1101-6 xxxxxxxxxx
8 Sebestyen A, Kovalszky I, Mihalik R, et al. Expression of syndecan-1 in human B cell chronic lymphocytic leukaemia. Eur J Cancer 1997; 33:2273-7 xxxxxxxxxx
9 Sebestyen A, Berczi L, Mihalik R, et al. Syndecan-1 (CD138) expression in human non-Hodgkin lymphomas. Br J Haematol 1999; 104:412-9
10 Gulyas M,Hjerpe A Proteoglycans and WT1 as markers for distinguishing adenocarcinoma, epithelioid mesothelioma, and benign mesothelium. J Pathol 2003; 199:479-87
This page last revised 1.11.2005.
©SMUHT/PW Bishop