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.

• myeloma^1,4 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

• a wide range of normal and tumoral epithelial cells^1,4, with positivity in some adenocarcinomas (particularly of lung and ovary) but negativity in most mesotheliomas:

		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	1/1 with 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