2004 Summer Meeting - Amsterdam - The Pathological Society of ...

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Osteoprotegerin is Overexpressed in Breast Cancers and
Intratumoural Endothelial Cells and is Significantly
Associated With Tumour Grade But Not With Axillary
Lymph Node Metastasis
SS Cross 1 , SP Balasubramanian 2 , CA Evans 3 , MWR Reed 2 , I
Holen 4
1 Academic Unit of Pathology, School of Medicine & Biomedical Sciences,
University of Sheffield, Sheffield, United Kingdom, 2 Academic Surgical
Oncology Unit, School of Medicine & Biomedical Sciences, University of
Sheffield, Sheffield, United Kingdom, 3 Histopathology Department,
Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom, 4
Academic Unit of Clinical Oncology, School of Medicine & Biomedical
Sciences, University of Sheffield, Sheffield, United Kingdom
Osteoprotegerin (OPG) is a protein, physiologically involved in control of bone
growth, which has been shown to act as a decoy receptor for tumour necrosis
factor related apoptosis inducing ligand (TRAIL) and thus to act as a tumour
cell survival factor in vitro. We have shown that OPG is not expressed in
normal breast tissue but is strongly expressed in luminal epithelial cells with
columnar change. In this study we look at OPG expression in breast cancers and
analyse its expression in relation to surrogate markers of tumour
aggressiveness. 400 invasive breast cancers (20% grade 1, 50% grade 2, 30%
grade 3) were sampled in triplicate in tissue microarrays and
immunohistochemistry for OPG was performed. There was strong
immunohistochemical expression of OPG in 40% of tumours. It was also noted
that intratumoural endothelial cells showed strong expression of OPG in 37% of
tumours. There was a significant decrease in tumour expression of OPG with
increasing tumour grade (p=0.001) but a significant increase in intratumoural
endothelial cell OPG expression with increasing tumour grade (p=0.004). There
was no significant association between either protein and axillary lymph node
metastasis (p=0.48, p=0.44 respectively). There was no significant association
between tumour cell and endothelial cell OPG expression (kappa=-0.17).
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Lymphocytic Lobulitis In Breast Core Biopsy: A Peritumoural
Phenonemon
AG Douglas-Jones
Department of Pathology, University of Wales College of Medicine, Heath
Park, Cardiff. CF4 4XW., Cardiff, United Kingdom
The aim of this study is to describe two cases of breast carcinoma
associated with an intratumoural lymphocytic infiltrate and peritumoural
lymphocytic lobulitis. In both cases initial core biopsy showed lymphocytic
lobulitis only but subsequent investigations showed an adjacent invasive ductal
carcinoma. Both carcinomas were grade 3 with extensive lymphocytic infiltrate
(lymphoepithelioma-like) and showed peritumoural lymphocytic lobulitis
extending for 7 mm beyond the margins of the invasive tumour. The infiltrating
cells were predominantly of T lineage and the affected lobular breast epithelium
expressed HLA DR suggesting an autoimmune pathogenesis.
Although diabetic mastopathy may present as a breast mass associated with
lymphocytic lobulitis, the cases presented illustrate that lymphocytic lobulitis in
core biopsy may represent a peritumoural phenomenon and further
investigation is required.
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E-Cadherin Expression In Invasive Non-Lobular Carcinoma
Of The Breast And Its Prognostic Significance
E.A Rakha , D.A Abd El-Rehim , S.E Pinder , I.O Ellis
Nottingham City Hospital, University of Nottingham, Nottingham, United
Kingdom
E-cadherin is a cell adhesion molecule expressed in normal breast tissue and
absence of its expression is a characteristic feature of lobular carcinomas.
However, in the more frequent non-lobular tumours, its biological and
prognostic value is still unclear. Material and Methods: In the current study, E-
cadherin expression was assessed immunohistochemistry in a large and well
characterized series of invasive non-lobular breast carcinoma (n=1516) with a
long term clinical follow-up (median of 56 months), using tissue microarray
technology, to determine the relationship between its expression and primary
tumour characteristics and disease outcome. Results: Membranous expression
of E-cadherin was detected in 92.8% of cases. A significant correlation was
found between absent or reduced expression of E-cadherin and indicators of
poor prognosis including larger tumour size, higher histological grade,
development of distant metastasis, regional and local recurrence, tumours
negative for estrogen receptors and those positive for p53. No correlation was
found between E-cadherin expression and lymph node status. Univariate and
multivariate analyses showed that E-cadherin is an independent prognostic
indicator of disease free survival and overall survival. The highest significance
was detected among patients with definite vascular invasion and those with
positive lymph nodes and to a lesser extent in those with bigger tumour size and
p53 positivity. Conclusion: These results suggest that E-cadherin may play a
role in progression, development of distant metastasis and recurrence in the
non-lobular carcinomas of the breast and its immunostaining can be used
efficiently in finding patients with poor outcomes especially in those with
vascular invasion and positive lymph nodes.
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Expression of E2F-4 in invasive breast carcinomas is
associated with poor prognosis
E.A Rakha , C.E Paish , S.E Pinder , I.O Ellis
Nottingham City Hospital, Nottingham University, Nottingham, United
Kingdom
The E2F family of transcription factors plays a key role in the control of
cellular proliferation and apoptosis. Some family members act as oncogenes,
others act as tumour suppressor genes (TSGs), behaviour which appears to be
tissue specific. E2F-4 is a member of the E2F family located at the
chromosomal band 16q22.1 that shows frequent deletion in breast cancer. In
the present study, the expression of E2F-4 was assessed
immunohistochemically on paraffin sections from 265 cases of breast
carcinoma and the expression was compared to both clinicopathological
variables and disease outcome. E2F-4 protein expression was detected in the
nuclei and in the cytoplasm of normal and malignant epithelial cells of the
breast. In the malignant tissues, no significant loss or decrease of expression
was seen in association with any specific tumour type. There was a correlation
between increased nuclear expression of E2F-4 and indicators of poor prognosis
including larger tumour size (p=0.000), grade 3 lesions (p=0.033), lymph node
stage (p=0.037) and poorer Nottingham Prognostic Index group (p=0.003).
Also, with the development of recurrent disease (p=0.004), distant metastasis
(p=0.001) and poorer outcome including poorer overall survival time (p=0.002)
and shorter disease free interval (p=0.001). In multivariate analysis, E2F-4 was
of an independent prognostic significance along with grade and lymph node
stage. These results suggest that E2F-4 may play a role in breast cancer
progression and that increased nuclear expression is associated with the more
advanced tumours with poor outcomes. E2F-4 appears to have an oncogenic
role rather than a tumour suppressor role in breast carcinogenesis and hence, it
is not the gene targeted by 16q22.1 loss in the carcinoma of the breast.
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