Artikel
CD74 expression in tumor cells is a positive prognostic marker for brain metastases patients
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Autoren
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Pia S. Zeiner
- Goethe-University, Edinger-Institute, Frankfurt am Main, Germany; Goethe-University, Department of Neurology, Frankfurt am Main, Germany
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Simon Bernatz
- Goethe-University, Edinger-Institute, Frankfurt am Main, Germany
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Michael W. Ronellenfitsch
- Goethe-University, Dr. Senckenberg Institute of Neurooncology, Frankfurt am Main, Germany
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Jenny Zinke
- Goethe-University, Edinger-Institute, Frankfurt am Main, Germany
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Frits Thorsen
- University of Bergen, Department of Biomedicine, Bergen, Norway
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Karl H. Plate
- Goethe-University, Edinger-Institute, Frankfurt am Main, Germany
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Rudi Beschorner
- University of Tuebingen, Department of Pathology and Neuropathology, Tuebingen, Germany
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Benjamin Weide
- University of Tuebingen, Department of Dermatology, Tuebingen, Germany
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Jörg Wischhusen
- University of Wuerzburg, Department of Gynecology, Wuerzburg, Germany
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Michel Mittelbronn
- Goethe-University, Edinger-Institute, Frankfurt am Main, Germany
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Patrick N. Harter
- Goethe-University, Edinger-Institute, Frankfurt am Main, Germany
| Veröffentlicht: | 25. August 2015 |
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Gliederung
Text
The macrophage migration inhibitory factor (MIF) receptor CD74 (also known as invariant chain) is upregulated in numerous peripheral neoplasms and has also been described as one of the most overexpressed molecules in primary brain tumors. While under certain circumstances MIF-CD74 interactions, lead to a pro-tumorigenic signaling cascade in tumor cells, there is also evidence, that CD74 expression in tumor cells might be a positive prognostic factor for patient survival. Besides the function as MIF receptor, CD74 is associated with MHC class II molecules acting as a chaperone in the process of antigen processing. We recently discovered CD74 as an exclusive marker for microglia and macrophages in primary brain tumors, while here we describe CD74 expression additionally on tumor cells of brain metastases.
We analyzed CD74, MHC-II and MIF expression by immunohistochemistry using tissue micro arrays of 181 brain metastases patients. Expression was compared to clinical data, especially with regard to tumor subtypes and patient survival.
Our data indicate, CD74 expression in tumor-associated microglia/macrophages (TAMs) and occasionally reactive astrocytes, but also in tumor cells of particular human brain metastases. Among others we found positive tumor cells in renal cell carcinomas (RCC) (10/10; 100% of tested tumors), colon carcinomas (5/7; 71% of tested tumors), non small cell lung cancers (NSCLC) (19/31; 61% of tested tumors), breast carcinomas (10/16; 62% of tested tumors) and melanomas (25/87; 28% of tested tumors). MIF expression was found in almost all tested samples in varying intensity with highest levels in RCC, melanoma and NSCLC brain metastases. MHC class II expression was found in around one-fourth of analyzed tumor samples (RCC: 10%; colon carcinomas: 0%; NSCLC 25%; breast carcinomas 25%; melanomas 29%). Most interestingly, CD74 expression in tumor cells of brain metastases was associated with beneficial patient survival in the whole cohort (p<0.0001) as well as in the subcohort of melanoma brain metastases (p=0.03).
Additionally, CD74 expression in tumor cells was strongly associated with tumor infiltrating lymphocytes (TILs), suggesting that CD74 is involved in a pro-inflammatory, anti-tumor response, potentially by mediating antigen processing.
