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abstract & commentary
Synopsis: Nasopharyngeal cancer cells were shown to express IL-10 by immunohistochemistry. The results of this study imply that expression of IL-10 is a prognostic factor in patients with nasopharyngeal cancer and may prove useful in development of treatment strategies.
Source: Fujieda S, et al. Cancer 1999;85:1439-1445.
Interleukin-10 (il-10) is an important modulator of lymphocyte function with generally immunosuppressive properties.1 Its production by a variety of tumor cells including lymphoma2 and melanoma3 has been associated with more aggressive tumor characteristics, and shortened survival. The association between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) has been appreciated for two decades. Recently, EBV-encoded RNA signals were identified in nuclei of malignant cells in 96.4% of primary NPC tumors.4 It has now also been appreciated that the EBV genome produces a protein (designated viral-IL-10) with extensive homology to human IL-10, and like human IL-10, v-IL-10 inhibits cytokine production by human peripheral blood mononuclear cells.4
In this report, Fujieda and colleagues investigated the expression of IL-10 in 21 primary nasopharyngeal cancers using immunohistochemical techniques. IL-10 staining was positive in 12 of 21 (57%). There was no association between IL-10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between those that stained negative and positive for IL-10. Although 87% of the IL-10 negative group survived for five years, only 15% of the IL-10 positive patients survived that long. Using multivariate analysis, IL-10 expression was significant as an independent prognostic indicator of overall survival. Fujieda et al propose that IL-10 staining of primary NPC may be useful in selecting patients at all stages for aggressive treatment.
Fujieda et al found that there was a bimodal distribution of IL-10 expression in tumors from patients with NPC. An IL-10 staining score of less than 10% was considered negative, whereas a score of more than 30% was positive. The IL-10 score in patients with Stage IV disease was higher than those with Stage II or Stage III, but this difference was not significant by one-way analysis of variance. Furthermore, there was no association between IL-10 expression and tumor size, lymph node status, clinical stage, or recurrence. Yet, the IL-10 score was significantly correlated with death from disease. Nine patients died of disease in this study, and their IL-10 staining score was 65%, compared to a score of 28% in those who survived.
Thus, IL-10 staining was a useful independent prognostic indicator in patients with NPC. Why this would be the case is a matter of conjecture. However, it might relate to the function of IL-10, which is generally immunosuppressive. Not only does IL-10 inhibit other cytokine production, it has been shown to inhibit specific T-cell functions, antigen presentation, and macrophage function in various tumor immunity models.5-7 A local production of IL-10 within the NPC microenvironment might undermine local immune or inflammatory responses that would otherwise inhibit growth.
Another proposed mechanism of tumor-enhancement by IL-10 relates to its potential as a direct growth factor. For example, melanoma cells have been shown to express both IL-10 and IL-10 receptor, and anti IL-10 antibody decreased spontaneous proliferation of cells.8 This would suggest that IL-10 might function as an autocrine growth factor for melanoma. Whether this is true for other tumor types, such as NPC, remains to be investigated.
Finally, IL-10 staining in NPC tumors may well relate to its association with EBV. The strong association with IL-10 expression and patient survival suggests that its immunosuppressive, or direct tumor- enhancing properties, may be of clinical importance. High tumor IL-10 expression was found in approximately one-half of NPC patients, and it was a strong, independent predictor of survival. Clinicians and clinical investigators might benefit from assessing this tumor characteristic when developing treatment strategies.
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a. correlate with primary tumor size.
b. correlate with lymph node status.
c. correlate with patient survival.
d. all of the above.
e. none of the above.