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

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1<br />

Validation <strong>of</strong> Tissue Microarray Technology using Cervical<br />

Adenocarcinoma and its Precursors as a Model System<br />

MMT EL-Mansi , DJ Harrison , ARW Williams<br />

Edinburgh Medical school, Edinburgh, United Kingdom<br />

<strong>The</strong> recent development <strong>of</strong> tissue microarray (TMA) technology has potentiated<br />

large-scale retrospective cohort studies using archival formalin-fixed, paraffinembedded<br />

tissues. One obstacle to broad acceptance <strong>of</strong> TMAs is that they<br />

reduce the amount <strong>of</strong> tissue analyzed from a whole tissue section to a disk <strong>of</strong><br />

0.6mm diameter. In this study, we used a large series <strong>of</strong> cervical adenocarcinomas<br />

to investigate TMA technology in assessment <strong>of</strong><br />

immunohistochemical staining. A TMA was constructed using 273 archival<br />

paraffin blocks from a series <strong>of</strong> 139 patients with 119 invasive and 20<br />

preinvasive cervical adenocarcinomas, and 16 normal controls. Two cores were<br />

obtained from specific regions <strong>of</strong> donor blocks selected at histological review,<br />

and subsequently were arrayed into a recipient block. <strong>The</strong> novel array blocks<br />

and some whole donor blocks were sectioned and used for immunohistochemical<br />

analysis for CEA, CK7 and CK20. We compared staining in the<br />

microarray disks with the whole tissue sections. <strong>The</strong> TMA was found to yield<br />

good immunohistochemical staining which was concordant with that <strong>of</strong> the<br />

whole section from which it originated. Two TMA cores achieved<br />

representation <strong>of</strong> the whole section in immunohistochemical studies in over<br />

95% <strong>of</strong> cases. Our results suggest that TMAs can be successfully used for<br />

immunohistochemical studies <strong>of</strong> cervical adenocarcinomas. <strong>The</strong> TMA<br />

technique is a rapid, cost effective, and tissue-saving method for highthroughput<br />

immunohistochemical studies. <strong>The</strong> areas sampled from donor<br />

blocks must be selected by careful review <strong>of</strong> sections from the original blocks,<br />

and we have shown the cores to accurately represent the morphology <strong>of</strong> the<br />

tumour in all cases. Two cores will provide representative<br />

immunohistochemical results in over 95% <strong>of</strong> cases.<br />

2<br />

BMD In hrHPV Positive Women Is Age Dependent And Is<br />

Probably A Cytopathological Effect Of A Primary HrHPV<br />

Infection<br />

NWJ Bulkmans 1 , L Rozendaal 1 , PJF Snijders 1 , FJ Voorhorst<br />

1 , AJP Boeke 1 , GRJ Zandwijken 1 , FJ van Kemenade 1 , RHM<br />

Verheijen 1 , K van Groningen 2 , ME Boon 3 , HJF Keuning 4 , M<br />

van Ballegooijen 5 , AJC van den Brule 1 , CJLM Meijer 1<br />

1 VU Universtity Medical Centre, <strong>Amsterdam</strong>, Netherlands, 2<br />

Spaarneziekenhuis, Heemstede, Netherlands, 3 Leiden Cytology and<br />

Pathology Laborotory, Leiden, Netherlands, 4 Stichting PA Laboratorium<br />

Kenemmerland, Haarlem, Netherlands, 5 Erasmus Medical Centre,<br />

Rotterdam, Netherlands<br />

POBASCAM is a population-based randomised-controlled trial to implement<br />

hrHPV-testing in cervical screening, comparing hrHPV-testing & cytology with<br />

cytology & hrHPV-blinded. Here, we present the baseline data.<br />

Between January 1999 and September 2002, 44,102 women, mean age 42.8<br />

years, were included. <strong>The</strong> presence <strong>of</strong> hrHPV was age-dependent, decreasing<br />

from 12.0% at 29-33 years to 2.4% at 59-61 years. In the intervention group the<br />

distribution <strong>of</strong> cytology hrHPV by cytology class was normal cytology 96.6%<br />

(3.6% hrHPV-positive), borderline and mild dyskaryosis (BMD) 2.5% (34.6%<br />

hrHPV-positive), and moderate dyskaryosis or worse (>BMD) 0.8% (88.3%<br />

hrHPV-positive). In the control group, 96.5% normal cytology, 2.4% BMD and<br />

0.8% >BMD. When stratified to hrHPV-status, in hrHPV-negative women the<br />

prevalence <strong>of</strong> BMD or >BMD were low and independent <strong>of</strong> age. In hrHPVpositive<br />

women, the prevalence <strong>of</strong> >BMD (13.7%) was also independent <strong>of</strong> age,<br />

i.e., women with an hrHPV-infection have a flat risk <strong>of</strong> having severe cervical<br />

lesions. In contrast, in women with a positive hrHPV-test the prevalence <strong>of</strong><br />

BMD was age-dependent, (p for trend

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