Expression of interleukin 6 (IL-6) correlates with oestrogen receptor in human breast carcinoma

Abstract

Multifunctional cytokines play important and only partially defined roles in mammary tumour development and progression. Normal human mammary epithelial cells constitutively produce interleukin 6 (IL-6), IL-8 and a non-secreted form of tumour necrosis factor. Transformation of mammary epithelial cells by different oncogenes is frequently associated with alterations of cytokine/growth factor production and responsiveness. In the present study we analysed the expression of IL-6 in 149 cases of invasive breast carcinoma and the data have been correlated with clinico-pathological variables including tumour size, histological grade, nodal status, and oestrogen and progesterone receptors, Ki67 and p53, protein expression. Though the majority of breast carcinomas expressed at least low levels of immunoreactive IL-6, we found that expression of this cytokine was inversely associated with histological tumour grade ( P = 0.0017), but not with tumour size and nodal status. Ki67 positivity was inversely correlated with IL-6 expression ( P = 0.027). Among biological parameters analysed, a direct association was found between the percentage of IL-6-positive cells and that of oestrogen ( P = 0.00005) and progesterone ( P = 0.025) receptor-positive cells. No correlation was observed between IL-6 and p53 protein expression. These data indicate that down-regulation of IL-6 is associated with highly malignant mammary carcinomas. It will be of interest to evaluate whether alterations of cytokines that are constitutively produced by mammary cells are also associated with high-grade tumours. © 1999 Cancer Research Campaign

IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

“…On the contrary, other studies show that IL-8 expression in breast tumors is identical between normal and cancer tissues (Speirs et al, 1996). Interestingly, IL-6 expression has been correlated with ER status (Fontanini et al, 1999), which suggests that IL-6 and IL-8 are opposite markers.…”

Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients

“…This suggests that, apart from the regulatory effects of IL-6 on VEGF production, other mechanisms are responsible for the deleterious effects of high serum IL-6 levels on tumour growth, thus explaining their strong correlation with prognosis in metastatic breast cancer patients. Although IL-6 expression in early-stage breast carcinomas has been correlated with low grade, oestrogen receptor status and good prognosis (Fontanini et al, 1999;Karczewska et al, 2000), several studies have shown that IL-6 may contribute to disease progression, particularly in advanced breast cancer patients. Indeed, IL-6 can modulate steroid hormone responsiveness by increasing aromatase activity and oestradiol 17 beta-hydroxysteroid dehydrogenase activity in malignant tissue and by activating oestrogen receptor-a (Duncan et al, 1994;Singh et al, 1999;Speirs et al, 2000).…”

RET protein expression has no prognostic impact on the long-term outcome of papillary thyroid carcinoma

“…Sections were scored independently by two pathologists (F B and L P) using a method described previously (25): the intensity of staining was scored from 0 to 3 (0=absent; 1=weak; 2=moderate and 3=strong); the proportion of malignant cells positively stained was scored from 0 to 4 (0=no positive cells; 1 # 10% positive cells; 2 11±50%; 3 51±75% and 4 76±100%). The two scores were added to yield the total score (0±7).…”