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

213
Microarray Based Comparative Genomic Hybridization For
Genomic Profiling In Pathology
GA Meijer
VU University Medical Centre, Amsterdam, Netherlands
Histological grading and typing for classifying tumor samples into clinically
meaningful categories is one of main tasks in diagnostic pathology. For a long
time this was mainly based on H&E stainings, later supplemented with
immunohistochemistry and recently extended with genomic profiling at the
DNA, mRNA or protein level. DNA based profiling is attractive because DNA
is easy to handle in a routine pathology setting, it can be isolated from archival
material, and data interpretation is rather straight forward. The state of the art
tool for obtaining DNA based genome wide tumour profiles is microarray based
comparative genomic hybridization, a technique that especially the last year has
become more widely available.
Applications in pathology include identification of new oncogenes and
tumor suppressor genes, discovery of new tumour classes and correlation to
clinical outcome, including response to therapy. Such studies will provide
classification rules that can be used to assign individual samples into the
appropriate diagnostic category. Other applications include genomic
comparison of multiple tumours within one patient as well as assessment of
chromosomal aberrations in perinatal pathology and clinical genetics.
New developments include full genome covering arrays, oligonucleotide
based platforms and PCR based approaches like multiplex ligation-dependent
probe amplification
214
Tumour–Stroma Interactions In Melanoma
LCLT van Kempen , J Rijntjes , GNP van Muijen , DJ Ruiter
University Medical Centre, Dept. of Pathology, Nijmegen, Netherlands
Solid tumors are complex mixtures of neoplastic and non-neoplastic cells,
matrix proteins and soluble polypeptide growth factors. Neoplastic progression
of solid tumours is often characterized by an increased architectural disorder at
the invasive front, which results from a simultaneous increase in matrix
synthesis (e.g. type I collagen) by stromal cells and degradation by proteolytic
enzymes (e.g. matrix metalloproteinases). Type I collagen remodelling
attenuates apoptotic stimuli emerging from intact collagen, alters the
bioavailability of collagen-binding polypeptide growth factors, is a prerequisite
for angiogenesis, and enables expansive and invasive growth. However, with
the exception of desmoplastic melanoma, invasive human cutaneous melanoma
appears devoid of a strong stromal reaction. Type I collagen mRNA in situ
hybridization revealed increased synthesis by stromal cells juxtaposed to noninvasive
melanoma cell nests. In contrast, synthesis was not observed in stromal
cells adjacent to the invasive tumour component. This part of the tumor also
displayed pericellular proteolysis of the extracellular matrix as a result of
proteinase synthesis by tumour and stromal cells. In combination with altered
type I collagen synthesis by stromal cells, this further modulates the tumour
microenvironment. Fibroblasts are the predominant source of type I collagen in
skin. In vitro, only metastatic human melanoma cell lines inhibit type I collagen
synthesis by primary dermal fibroblast. These data indicate that type I collagen
synthesis in melanoma may be a host defence mechanism towards the neoplasm
but that melanoma cell-mediated inhibition of type I collagen synthesis enables
the transition from micro-invasive to deeply invasive melanomas with
metastatic capacities.
215
Evidence based dataset reporting for melanoma.
AT Evans
Ninewells Hospital and Medical School, Dundee, United Kingdom
Dataset reporting is now well established for common malignancies such as
breast and colorectal carcinoma but it has been slow to become established for
cutaneous melanoma. In 2001 SIGN (The Scottish Intercollegiate Guidelines
Network) formed a working party to examine the care pathway for patient’s
with melanoma in Scotland. Recognising that the pathology report is central to
deciding treatment and follow-up the aim of the pathology subgroup was to
foster a high standard of pathology reporting at a national level and also to
ensure that the clinician was provided with prognostically valid information.
A broad spectrum of histopathological variables was studied using
established SIGN methodology. The quality of the evidence base was scored
and a grade of recommendation derived for each variable. After examination of
the available published evidence the variables considered essential for inclusion
in the surgical report were as follows; Breslow thickness, Clark level (for
lesions