Diagnostic Value of Wilms Tumor 1 and CD44 in Langerhans Cell Sarcoma: Case Series of 4 Patients

2015-04-01 00:01:44

Medicine; April 2015;Vol.94;Iss.13;p.e636; DOI:10.1097/MD.0000000000000636

Wang, Chang-song PhD; Chen, Yan-ping MD; He, Wei-hua PhD; Yin, Jian MD; Gao, Chun-fang MD; Wang, Ping PhD; Li, Hong PhD; Lv, Xue-xia MD


Langerhans cell sarcoma (LCS) is a rare tumor with markedly malignant cytological features originating from Langerhans cells. LCS diagnosis is difficult and requires differentiation from other malignant tumors and Langerhans cell histiocytosis (LCH). Immunochemical antibodies, such as langerin, S-100 protein, and CD1a, have been used to diagnose LCS, but the results are crossed with LCH. To determine more significant biomarkers of LCS, we studied the expression and distribution pattern of Wilms tumor 1 (WT1) and cluster of differentiation 44 (CD44) in LCS.

A broad panel of antibodies was used for immunohistochemical technology. Simultaneously, dual immunofluorescence staining examination and fluorescence in situ hybridization staining methods were used to study the location of WT1 and CD44 in LCS tumor cells.

The results showed that tumor cells expressed WT1, CD44, and other special Langerhans cell markers (langerin, CD1a, and S-100 protein). LCS cells in all the cases showed normal cytogenetic findings without overexpression of WT1 and CD44. The expression of WT1 and CD44 was observed on langerin+ tumor cells by dual immunofluorescence staining examination in LCS.

Our results suggest that WT1 and CD44 are potential biomarkers for LCS diagnosis. Clear understanding of their functional roles may further explain the pathogenesis of this highly malignant tumor and develop some novel immunotherapy strategies.


Langerhans cell tumors include Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS). LCS is a rare malignant dendritic cell tumor that displays overtly malignant cytology that includes the Langerhans cell phenotype. The overall survival of LCS is ~50% within 1.5 years even after being administrated with a combination of radiotherapy and chemotherapy or with surgery and local radiotherapy.

LCS diagnosis is difficult and requires differentiation from other tumors such as metastatic cancer, malignant melanoma, anaplastic large-cell lymphoma, myeloid sarcoma, and malignant fibrous histiocytoma, as well as from LCH. Various immunochemical antibodies, such as langerin, S-100 protein, and CD1a, have been introduced for LCS diagnosis, but the results were not ideal. Thus, more specific biomarkers should be determined for the diagnosis and differential diagnosis of LCS.

Wilms tumor 1 (WT1) gene is originally isolated as a tumor suppressor gene inactivated in the childhood kidney neoplasm Wilms tumor. WT1 gene plays a biological role by regulating the expression of different genes, such as transforming growth factor β Bcl-2, and human telomerase reverse transcriptase. WT1 is also a transcriptional regulator that plays a central role in the development of several organs and tissues, such as kidneys, gonads, and spleen. Further research revealed that WT1 gene is overexpressed in various cancer cells, including leukemia, lung cancer, and breast cancer. These studies showed that WT1 expression is strongly associated with cancer progression and tumor-related patient prognosis. Additional studies demonstrated WT1 as an oncogene in several tumors.

Cluster of differentiation 44 (CD44) is a cell-surface transmembrane glycoprotein involved in cell–cell interactions, lymphocyte activation, cell adhesion, recirculation and homing, adhesion of extracellular matrix, and angiogenesis, as well as cell proliferation, differentiation, and migration. CD44 can also activate various receptor tyrosine kinases in many cancers. Moreover, CD44 plays an important role in invasion and metastasis of various tumor cells. These properties are associated with the pathologic activities of cancer cells.

However, WT1 and CD44 may serve as potential diagnostic and prognostic biomarkers, but no reports exist about the expression of WT1 and CD44 in LCS. In the present study, we detected the expression of the WT1 protein and CD44 in LCS using immunohistochemical and fluorescence detection to assay the expression of WT1 and CD44 on neoplastic cells and to estimate whether they serve as useful diagnostic and prognostic markers for LCS.

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