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

189
The Expression of S100A6 Protein in Human Tissues and
Common Tumours Outside the Central Nervous System
SS Cross 1 , FC Hamdy 2 , I Rehman 2
1 Academic Unit of Pathology, School of Medicine & Biomedical Sciences,
University of Sheffield, Sheffield, United Kingdom, 2 Academic Urology
Unit, School of Medicine & Biomedical Sciences, Sheffield, United
Kingdom
S100A6 is a member of the EF-hand type calcium binding protein family which
includes some proteins that have abnormal patterns of expression in human
cancer. The expression of S100A6 has not been systematically described in
human tissues and common cancers. We have performed an
immunohistochemical survey of S100A6 expression on a custom made tissue
array containing 291 tissue cores representing 28 human tissue types and 21
different tumour types. S100A6 was expressed in both the nucleus and
cytoplasm in cells where it was present. It was expressed in many epithelia
including ciliated columnar epithelium, glandular epithelium lining the gut,
ducts in the salivary glands, the endocervix, epithelia in the kidney, bilary
epithelium, but it was not expressed in the squamous epithelium of the skin nor
the endometrial epithelium. It was also expressed in melanocytes, nerve sheath
cells, Leydig cells in the testis, and endothelial cells (especially within
tumours). In neoplasia it was expressed in colorectal, ovarian, breast, bladder
transitional cell and some squamous cell cancers but was entirely absent in
cutaneous basal cell carcinomas. This widespread expression suggests that it
does not have a role as a marker in diagnostic histopathology but the
mechanism of its overexpression in cancers whose background epithelia do not
express it (e.g. squamous epithelium) may be interesting.
190
S100A8 Protein is Expressed in Neutrophils, Macrophages,
Some Breast Cancers and Some Squamous Cell Cancers
SS Cross 1 , FC Hamdy 2 , I Rehman 2
1 Academic Unit of Pathology, School of Medicine & Biomedical Sciences,
University of Sheffield, Sheffield, United Kingdom, 2 Academic Urology
Unit, School of Medicine & Biomedical Sciences, University of Sheffield,
Sheffield, United Kingdom
S100A8 (calgranulin A) is a member of the EF-hand type calcium binding
protein family which includes some proteins that have abnormal patterns of
expression in human cancer. S100A8 commonly forms a heterodimer with
S100A9 and is expressed in neutrophils and macrophages, its expression in
other tissues has not been systematically investigated. We have performed an
immunohistochemical survey of S100A8 expression on a custom made tissue
array containing 291 tissue cores representing 28 human tissue types and 21
different tumour types. There was expression of S100A9 in 2 cases of
cutaneous squamous carcinoma in situ, 1 invasive squamous cell carcinoma of
the uterine cervix and 12% of 41 breast cancers. The expression in breast
cancers is unexpected and has not been described before. Further investigation
is required to see if this expression relates to prognosis and whether it is due to
epigenetic factors (such as methylation) or genetic derangement of the q21
region of chromosome 1, the site of the majority of S100 genes.
191
S100A9 Protein is Overexpressed in Human Breast and
Squamous Cell Cancers
SS Cross 1 , FC Hamdy 2 , I Rehman 2
1 Academic Unit of Pathology, School of Medicine & Biomedical Sciences,
University of Sheffield, Sheffield, United Kingdom, 2 Academic Urology
Unit, School of Medicine & Biomedical Sciences, University of Sheffield,
Sheffield, United Kingdom
S100A9 (calgranulin B) is a member of the EF-hand type calcium binding
protein family which includes some proteins that have abnormal patterns of
expression in human cancer. S100A9 commonly forms a heterodimer with
S100A8 and is expressed in neutrophils and macrophages, its expression in
other tissues has not been systematically investigated. We have performed an
immunohistochemical survey of S100A9 expression on a custom made tissue
array containing 291 tissue cores representing 28 human tissue types and 21
different tumour types. There was expression of S100A9 in all squamous
epithelium, all squamous cell carcinomas (both in situ and invasive) and 28% of
40 breast cancers. The expression in breast cancers is unexpected and has not
been described before. Further investigation is required to see if this expression
relates to prognosis and whether it is due to epigenetic factors (such as
methylation) or genetic derangement of the q21 region of chromosome 1, the
site of the majority of S100 genes.
192
Microsatellite Genotyping to Compare Loss of Heterozygosity
in Choriocarcinomas and Placental Site Trophoblastic
Tumours
B Burke 1 , J Moss 2 , NJ Sebire 2 , MD Hodges 1 , RA Fisher 1
1 Imperial College London, London, United Kingdom, 2 Charing Cross
Hospital, London, United Kingdom
Our objectives were to analyse a series of choriocarcinomas and placental site
trophoblastic tumours (PSTTs) in order to refine the regions of chromosomal
loss previously described in choriocarcinomas and investigate these regions in
PSTTs. The PixCell II LCM system was used to capture tumour and maternal
tissue from H&E stained sections of formalin-fixed, paraffin-embedded blocks.
DNA was then extracted and fluorescent microsatellite genotyping performed
to assess the quality of the DNA and confirm the gestational origin of the
tumour. Tumour tissue was successfully microdissected and adequate DNA for
analysis prepared in ten tumours that were shown to have arisen in a complete
hydatidiform mole and twenty-five tumours originating in non-molar
pregnancies. A panel of microsatellite markers were then used to investigate
loss of heterozygosity (LOH) for the chromosomal regions 7p12-q11.23 1 and
8p21-p22 2 in these tumours. No homozygous deletions were identified in postmole
tumours for either region. In tumours that developed in non-molar
pregnancies LOH for 7p12-q11.23 was rare in both choriocarcinomas and
PSTTs. LOH for 8p21-p22 was found in a subset of choriocarcinomas, but not
in PSTTs. In conclusion this study does not support the previous observation
that LOH for chromosome 7 may be important in the development of
trophoblastic tumours.
Matsuda et al; 1997, Oncogene 15: 2773-81.
Ahmed et al; 2000, Cancer Genet Cytogenet 116: 10-15
74