Expression of interleukin-1beta in human breast carcinoma.
BACKGROUND
Interleukin 1beta (IL-1beta) is a multifunctional cytokine that up-regulates the inflammatory response. It is not known whether IL-1beta plays a major role in human malignancy. To determine whether IL-1beta might be involved in breast carcinoma progression, the authors measured the IL-1beta content in tissue extracts from >200 invasive breast carcinomas and smaller numbers of ductal carcinoma in situ (DCIS) and benign lesions.


METHODS
IL-1beta content was measured by an enzyme-linked immunoadsorbent assay and analyzed to determine whether these values were correlated with the contents of scatter factor (SF) (an invasogenic and angiogenic cytokine), von Willebrand's factor (VWF) (a marker of endothelium), thrombospondin-1 (TSP1) (an antiadhesive and antiangiogenic glycoprotein), and tumor necrosis factor-alpha (TNF alpha) (another proinflammatory cytokine). Studies were also performed to determine whether IL-1beta content was correlated with other pathologic and immunochemical variables that have been utilized or proposed as prognostic indicators for breast carcinoma.


RESULTS
The most important findings of these studies were: 1) immunoreactive IL-1beta was detected in approximately 90% of invasive breast carcinomas; 2) IL-1beta levels were significantly higher in invasive carcinomas than in a group of DCIS and benign lesions; 3) high IL-1beta content in invasive carcinomas was significantly associated with higher contents of SF, VWF, and TSP1, but not TNF alpha; and 4) there was a trend toward higher IL-1beta content in invasive carcinomas with a group of other parameters that suggest a biologically more aggressive tumor (estrogen receptor negativity, high tumor grade, p53 positivity, and bcl-2 negativity); and the proportion of invasive tumors with these characteristics was significantly increased in a subgroup of tumors having very high IL-1beta content. The authors also found a correlation between high IL-1beta content and CD68 positivity, suggesting that macrophages may account for some of the IL-1beta present in human breast carcinoma tissue.


CONCLUSIONS
These findings suggest that significant titers of IL-1beta are present within the microenvironment of most breast carcinomas and that a high IL-1beta content is often associated with tumor invasiveness and with other pathologic features suggestive of an aggressive tumor biology.
Jin
L
L
Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus for Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
Yuan
R Q
RQ
Fuchs
A
A
Yao
Y
Y
Joseph
A
A
Schwall
R
R
Schnitt
S J
SJ
Guida
A
A
Hastings
H M
HM
Andres
J
J
Turkel
G
G
Polverini
P J
PJ
Goldberg
I D
ID
Rosen
E M
EM
D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis*; D008207:Lymphatic Metastasis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D017228:Hepatocyte Growth Factor; D007375:Interleukin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor