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

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Human Papillomavirus DNA Vs mRNA: Clinical Indicators
for the development of cervical neoplasia ?
N Murphy 1 , H Skomedal 2 , M Oder Oye 2 , P Gronn 2 , IM
Falang 2 , O Sheils 3 , JJ O' Leary 4
1 Department of Pathology, The Coombe Women's Hospital and Trinity
College, Dublin, Ireland, 2 NorChip NS, Klokkarstua, Norway, 3
Department of Pathology, St. James's Hospital and Trinity College,
Dublin, Ireland, 4 Department of Pathology the Coombe Women's
Hospital, St. James's Hospital and Trinity College, Dublin, Ireland
The persistent activity of HPV oncogenes E6 and E7 are necessary
prerequisites for the development and progression of high-grade cervical
lesions and cervical cancer. Testing for HPV oncogenic activity rather than the
presence of HPV DNA may be a more relevant clinical indicator for the
development of cervical lesions and cervical cancer. The aim of this study was
to examine the correlation between HPV DNA detection and actual HPV
oncogenic expression in the context of increasing severity of dyskaryosis. A
second objective of this study was to examine the effect of co-infection of HPV
types and oncogenic expression as to date the effect of multiple HPV infections
and HPV type specific oncogenic expression remains unclear.
In this study HPV DNA and mRNA detection and typing was
carried out for four of the high-risk HPV types most frequently associated with
cervical cancer namely HPV 16, 18, 31 and 33. HPV analysis was preformed
on 10 normal ThinPrep samples and 30 ThinPrep samples exhibiting mild,
moderate and severe dyskaryosis. TaqMan Real-Time PCR was employed for
HPV DNA detection and typing. The PreTect HPV-Proofer (NorChip AS,
Norway) molecular test kit, which is based on Real-Time NASBA technology,
was employed for HPV mRNA detection.
This study demonstrated that HPV oncogenic expression increased with
increasing severity of dysplasia. Oncogenic activity was absent in up to half of
cases demonstrating mild dyskaryosis. In addition this study demonstrated that
the majority of HPV co-infection were composed of a single persistent
transcriptionally active HPV type (typically HPV16) and a non-active
potentially transient/silent HPV type. The results of this study indicate that the
use of HPV mRNA detection may be a more clinically significant indicator of
cervical dysplasia in both single and multiple HPV infections.
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Lack Of Interobserver Agreement In The Diagnosis Of
Endometrial Cytological Atypia And Endometrial
Hyperplasia
MJ Staunton 1 , PA Cross 2 , JN Bulmer 1
1 Department of Histopathology, Royal Victoria Infirmary, Newcastle upon
Tyne, United Kingdom, 2 Department of Histopathology, Queen Elizabeth
Hospital, Gateshead, United Kingdom
Aim: Published criteria are available to diagnose endometrial hyperplasia, with
or without cytological atypia (which have a different prognosis). We observed
discord in this area, both locally and in the National Gynaecological
Pathologist’s External Quality Assurance scheme. This study was designed to
assess the consistency of diagnosis of endometrial cytological atypia among a
group of specialist gynaecological pathologists.
Methods: 15 pipelle biopsies were chosen to include a range of histological
appearances from normal to adenocarcinoma. Nine pathologists independently
assessed each case (5 Newcastle, 4 Gateshead). The results were compared
between pathologists, with the original diagnosis and with outcome.
Results: Concordance was good at extremes of the spectrum from normal to
malignant. There was an unexpected wide range of answers offered for
hyperplasia (with or without atypia) and grade of atypia. Pathologists in one
centre were no more likely to be concordant with colleagues in their own
centre. The number of years of experience of individual pathologists did not
influence the findings.
Conclusions: The literature suggests that by rigorously applying specific
criteria, it is possible to reliably diagnose endometrial hyperplasia (with or
without cytological atypia) and that patients can be offered different treatments
on this basis. Our results challenge this assumption.
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SEROUS CARCINOMA OF THE OVARY: A LINK
BETWEEN RADIATION EXPOSURE AND RET/PTC-1
ACTIVATION?
RJ Flavin 1 , SP Finn 1 , P Symth 1 , M Ring 2 , EM O'Regan 1 , S
Cahill 1 , E Gaffney 1 , JJ O'Leary 1 , O Sheils 1
1 St. James Hospital and Trinity College Medical School, Dublin, Ireland,
2 Coombe Women's Hospital, Dublin, Ireland
RET/PTC is an activated form of c-ret, a proto-oncogene, which has been
linked, with the development of papillary thyroid carcinoma. RET/PTC
expression has not been looked at before in other papillary tumours despite
similar morphology. Furthermore, increased risk of epithelial ovarian
carcinoma has been described following diagnostic X-rays and radiation
therapy to the pelvis, and ret rearrangements following radiation have been
linked to papillary thyroid carcinoma.
Epithelial cells were laser capture microdissected from formalin-fixed,
paraffin-embedded papillary tumours (N=31 included 18 cases of serous
carcinoma of the ovary, 1 serous surface peritoneal carcinoma, 7 serous
carcinoma of the endometrium, 3 renal cell carcinoma, and 2 urothelial cell
carcinoma). Total RNA was extracted, and analyzed for expression of GAPDH
and ret/PTC-1 using real time RT-TaqMan®PCR.
Ret/PTC-1 transcripts were detected in 2 of 10 serous surface ovarian
carcinomas. Immunostains for TTF-1 and thyroglobulin were negative. One
patient having a 20-year long history of renal stones had episodic KUB X-rays
performed.
There may be a tenuous link between radiation with subsequent ret/PTC-1
activation and serous surface papillary carcinoma development.
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Development and Audit of a Risk Management System for the
Histopathological Reporting of Melanocytic Lesions
M Bamford , J Osborne , G Saldanha , A Fletcher
University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
Introduction: The purpose of the MDT meeting is for clinical review and to
allow standardised, co-ordinated clinical management of cancer cases. At the
skin cancer MDT, current methods only identify melanomas for discussion.
This paper develops a method to identify three additional groups of melanocytic
lesions that would benefit from discussion.
Methods: The clinicians quantitated their impression of likelihood of
melanoma. This was compared with the final histological diagnosis.
Clinicopathological discrepancies, naevi with high grade atypia and cases with
histological diagnostic uncertainty were identified. An anonymous survey was
administered to assess clinical management of atypical naevi.
Results: From 100 cases, 5 clinicopathological discrepancies, 6 naevi with high
grade atypia and 0 cases of diagnostic uncertainty were identified. It was
established that the clinical management of naevi with high grade atypia was
not standardised.
Discussion: Identification of clinicopathologically discrepant cases allowed the
possibility for histological error trapping. The questionnaire led to clearer
understanding of the implications of a diagnosis of naevus with high grade
atypia and the need for standardised treatment.
Conclusion: In addition to melanomas, the routine identification of certain
carefully selected melanocytic cases for discussion allows the MDT to move
closer to achieving its overall purpose.
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