Immunohistochemical staining of tumor necrosis factor-α and interleukin-10 in benign and malignant ovarian neoplasms

Abstract

Ovarian cancer is the ninth most common malignancy and the fifth leading cause of cancer death in women in the USA. The majority of malignant tumors of the ovary are diagnosed at an advanced stage, making it the most fatal gynecological cancer. The aim of the current study was to determine whether there are differences in immunohistochemical tissue staining of cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) between benign tumors and malignant primary ovarian cancer. In total, 28 patients undergoing surgery for ovarian cysts were evaluated, and a diagnosis of benign neoplasm (n=14) or malignant neoplasm (n=14) was determined. An immunohistochemical study of histological sections of ovarian tumors was conducted. The results were analyzed using Fisher’s exact test, with P<0.05 indicating a statistically significant difference. Immunohistochemical staining of IL-10 was increased in malignant tumors compared with benign tumors (P=0.0128). For TNF-α, the immunohistochemical staining was more intense in malignant neoplasms, however, a statistically significant difference was not observed. These results indicate that the analysis of cytokines may be useful as a potential tissue marker of ovarian malignancy.

TNF-α expression, risk factors, and inflammatory exposures in ovarian cancer: evidence for an inflammatory pathway of ovarian carcinogenesis?

“…In a small series of 25 cases, Takayama and colleagues showed positive TNF-α staining in 80% by immunohistochemistry but in only 35% by ISH suggesting non-specific immunoreactivity in the tumor cells[34]. Similarly, the distribution of TNF protein was noted to be different from that of TNF mRNA in a study by Naylor et al that showed majority of TNF protein localized to the stroma or the epithelial-stromal interface[35, 36] Others have used immunohistochemistry to evaluate expression of inflammatory markers, including TNF-α, IL-1, IL-6, IL-10, TGFβ and COX2, but have been limited either by high background on immunohistochemical staining[37] small sample size with a broad mix of benign and malignant ovarian tumors[38] or by lack of well annotated clinical data in order to detect significant epidemiological associations. TNF-α has also been evaluated in ovarian cancer by gene expression arrays but these are limited by their inability to distinguish between TNF-α expression by tumor cells versus tumor infiltrating inflammatory cells[19].…”

Tumor necrosis factor receptor modulator spermatogenesis‐associated protein 2 is a novel predictor of outcome in ovarian cancer

“…Furthermore, Charles et al demonstrated that chronic production of TNF‐α in the tumor microenvironment increases myeloid cell recruitment and consequently tumor growth in vivo. Previous studies demonstrated an increase of TNF‐α protein and gene expression in human OC compared with non‐malignant controls . High ascitic TNF‐α protein levels have previously been found to be associated with poor survival in univariate analyses, however, data concerning intra‐tumor TNF‐α expression and clinical outcome are not available.…”

“…High ascitic TNF‐α protein levels have previously been found to be associated with poor survival in univariate analyses, however, data concerning intra‐tumor TNF‐α expression and clinical outcome are not available. In line with previous data, we demonstrate high levels of TNFA in human OC compared with non‐malignant control tissues . However, we were unable to determine a significant prognostic effect of TNFA expression in OC patients.…”

Interleukin-17 augments tumor necrosis factor α-mediated increase of hypoxia-inducible factor-1α and inhibits vasodilator-stimulated phosphoprotein expression to reduce the adhesion of breast cancer cells

“…TNF-α has been demonstrated to possess anti-tumor activity as it has cytostatic and cytotoxic effects on a number of cancer cell lines (2). However, previous studies have demonstrated that TNF-α may also affect matrix degradation and mediate the development of tumor metastases (3,4). Additionally, TNF-α regulates the expression levels of cell adhesion proteins and therefore may serve a role in determining the metastatic phenotype of tumor cells (5,6).…”