Congress Highlights
|
Slide
Seminars
Every case in every seminar is an in-depth approach to a case presented
by an expert. The “glass slide” for discussion is presented
in the form of digital images taken to simulate the way a pathologist
examines a slide. Many cases include other material necessary for making
a diagnosis in a routine laboratory – Xrays, gross, endoscopy, special
stains, frozen sections, other sections that illustrate additional features
of the case.
All of the images (with captions that indicate the important diagnostic
features) are reproduced in a book, together with further information
on the case, and a Commentary on the case with references. The book and
CD can be filed on a book-shelf which makes them easily accessible for
future study or reference.
Another big advantage is that every seminar done in this way can be purchased
by anyone in the world as well as by those who actually attend the Congress.
There is no limit to the number of slide seminars that can be
ordered.
Symposium on Grossing (Cut-ups) being done by Scientists
Friday Afternoon
Everywhere, pathologists are facing increasing work loads, and there is
a world-wide shortage of Pathologists. One means of relieving this problem
is to recruit scientists to assist in grossing. In the U.S., courses have
been devised to give scientists a post graduate diploma that allows them
to become Pathologists’ Assistants. Similar courses are being introduced
in other countries. The leading speakers at the Symposium will be expert
scientists from the US and the UK. It will provide a forum in which this
topic can be discussed from an International perspective.
Symposium on International Recognition of National
Specialist Training with Particular Reference to Pathology
Tuesday Afternoon
International recognition of medical specialist trainings and certifications
is at this moment still at an embryonal level. Except for the countries
of the European Union, that have reciprocity for each others diplomas,
this phenomenon is hardly known in other continents, and certainly not
between different continents. Nevertheless for the quality of medical
professions world wide, a system leading towards international recognition
and certification would be an enormous step forward. In this symposium
professionals in this field will discuss the problems and barriers that
block this process till now and they will discuss possible solutions.
Infectious Diseases a Global Perspective
Thursday - There will be a whole day symposium seminar.
A number of well credentialled and respected international speakers will
be giving us the lowdown on what’s new in infectious diseases.
In the morning the emphasis will be on the histology of new and emerging
pathogens, beginning with an introduction to the global aspects of infectious
diseases pathology by Dr Ann Marie Nelson, Chief, AIDS Pathology Branch,
Armed Forces Institute of Pathology, and continuing with a global emphasis
with speakers from the USA, Japan, Britain, South Africa and India.
The afternoon session is divided into two parts. The first is a continuation
of the morning’s theme with a talk on tropical infectious disease
pathology in Malaysia by Dr Norain Karim Followed by a “cook’s
tour” of tropical pathogens in Far North Queensland and the Torres
Strait, by Dr John McBride.
Following afternoon tea the emphasis will shift to Mycobacterium ulcerans,
a ubiquitous worldwide pathogen, with special significance to Australia.
The seminar will include individual talks on the clinico-pathological
classification and the pathology of Mycobacterium ulcerans infection followed
by an expert panel discussion.
Friday Morning - Slide Seminar
This will feature a number of “emerging virus Infections”
that jump the species barrier from animals to humans. A group of Infectious
diseases Physicians, Microbiologists and Pathologists will present 3 human
cases of a new virus that appeared in Brisbane- the Hendra virus.
On Friday afternoon, the Aust Soc of Veterinary Pathologists will hold
a session in which they will demonstrate cases of animal disease that
can cross the species barrier to infect humans.
History of Pathology Session
Monday Morning
A Brisbane surgeon who was brought up in Tropical North Queensland will
set the scene for the other presentations in this session. He will describe
the very basic nature of medical services and hospital facilities that
were available there before 1900.
The following speakers will tell how 3 Queensland doctors who worked in
the subsequent 20 year periods, all with very limited facilities, made
discoveries of international significance – The parasite of Filariasis,
Q fever and Apoptosis.
Palaeopathology
Monday Afternoon
We will be told about the interesting medical facts that have emerged
from the studies conducted on the mummified remains of ancient Peruvian
people over a period of 40 years of continuous investigations.
A member of the Archaeology Department of the Univ. of Queensland will
demonstrate the results of a new DNA test for identifying the presence
of various infectious diseases in bones from previous generations.
Australia is rich in the fossilized skeletal remains of Dinosaurs. Numerous
fossilized bones of the pre-cursors of Australia’s unique mammals
have recently been discovered. The Curator of fossils at the Queensland
Museum is Australia’s expert on this topic. He is young and a dynamic
speaker. He will talk about the pre-historic mammals, and demonstrate
some of the pathological conditions that they exhibit.
Breast Pathology
A wide range of topical issues in breast pathology will be presented over
4 half-day sessions on Monday morning and afternoon, Tuesday morning and
Wednesday afternoon. Speakers from all continents are represented in the
symposia, slide seminar and presentation of papers sessions (the latter
on Wednesday morning). The symposium on assessment of risk of malignant
breast disease includes a review of screening mammography, genetic predisposition
in breast cancer (including BRCA 1 and 2 status), interpretation of atypical
epithelial hyperplasias, classification of in situ carcinoma (with a summary
of the latest WHO “Blue Book” Ductal carcinoma in situ classification)
and cytomorphology of borderline breast lesions. Further cytological aspects
of breast disease will be presented in the companion cytology meeting
following the IAP Congress.
New molecular techniques and the value of assessing genotype in breast
tumours, with potential future prognostic implications, will be covered
in a session on “The pathologist and the role of targeted therapy”
on Monday morning. An Oncologist with extensive experience in the treatment
of breast cancer will present the relationship between pathological prognostic
markers and current and future “biologic” targeted therapies.
The sessions on “Optimal pathology reporting” will discuss
standardisation of hormone receptor analysis and Her 2 testing in addition
to optimal processing and assessment of sentinel lymph nodes. An overview
of sentinel node trials in Europe will be presented and representatives
from Europe, the United Kingdom and Australia will discuss the quality
assurance programs in place for practising pathologists. On Monday lunch
time the keynote address will be presented by Professor Vincenzo Eusebi
from the University of Bologna, Italy, on the contribution of pathologists
to classification, biological behaviour and treatment of breast cancer.
In the slide seminar on Wednesday afternoon 10 interesting cases from
the United Kingdom, United States of America, Hong Kong, Japan, Thailand
and Australia will be presented. Further information on the slide seminar
is available elsewhere on the website: http://www.iap04.im.com.au
Short Course – Recent Advances in Immunohistology
Course description: Six experts in immunohistology will discuss newer
aspects of antigen retrieval, objectivity in molecular morphology, the
biology of and evolution of neoplasia in the cervix and immunohistological
diagnosis of neoplasia in the female genital tract, breast and neuroendocrine
tumors.
“Arkadi M. Rywlin International Pathology
Slide Seminar”
Friday Morning
This a voluntary organization created more than 10 years ago to foster
the exchange of ideas and of interesting cases among a select group of
Academic Surgical Pathologists throughout the world. The present course
represents an extension of this concept. Twelve cases will be presented
and discussed by members of the Club. The cases selected will include
controversial topics which are discussed in an eclectic and provocative
fashion, with an aim to stimulate new and original approaches to the understanding
of the topic. Registrants will receive a set of glass slides and a comprehensive
handout.
Paediatric/Perinatal
Monday Morning
This symposium will be an educational morning focussing on Developments
on perinatal and paediatric pulmonary pathology. We will start with a
presentation on experimental and interventional studies on pulmonary hypoplasia
in animals and humans. This leads nicely into a state-of-the-art lecture
on fetal lung vascular development - including molecular mechanisms -
and implications for lung function. The third lecture continues this molecular
theme by presenting the range of pathological findings in lung biopsies
in infants and the correlation with some developmental surfactant mutations.
This will be followed by two talks that link congenital pulmonary abnormalities
with adult pulmonary disease. The last talk will be on lung tumours in
childhood.
Monday afternoon
The theme of this session is the autopsy and long term outcomes. We are
grateful to have a neonatologist provide us with the epidemiology and
scope of cerebral palsy. The pathology of cerebral palsy will be extensively
illustrated in the next talk. The importance of the autopsy will be illustrated
by the third talk, which will detail the extent of antepartum brain injury.
The next talk will critically review the contribution of the placenta,
in particular two poorly understood lesions, in adverse pregnancy outcome.
The last talk will demonstrate again the value of the autopsy by outlining
the natural and non-natural causes of neonatal sudden death.
Tuesday Morning
The overall theme of this Short Course session is advances in paediatric
tumour pathology. This will include classification, pathogenesis, diagnosis
and application of molecular techniques to diagnosis and classification.
As evident from the programme, the speakers will share their wealth of
experience on liver, Ewing’s and other bone tumours, paediatric
soft tissue tumours and dysgenetic gonadal tumours.
Tuesday Afternoon
This will be a very informative Slide Seminar session. There will be three
cases of tumours in the urinary tract, including a mimic, and three cases
of soft tissue tumours. Two other tumour cases will illustrate two points:
esoteric disease can present in childhood and there is always a seemingly
simple diagnostic modality. There are two non-tumour cases that will remind
us of rare and recently described entities.
Surgical Pathology Potpourri: A Singapore/Malaysia
Experience
Surgical pathology with a South East Asian flavour! A Singapore-Malaysia
Experience! A selection of interesting and unusual cases involving the
breast, bone, gastrointestinal tract, liver, lung and lymph node will
be presented. Participants will be given an insight to the diagnostic
dilemmas encountered in establishing the correct diagnosis. Some of the
cases are problematic, with benign lesions mimicking malignant tumours
and vice versa e.g a unique lung tumour with goblet cells. Others are
peculiar to this region e.g. an uncommon parasitic infestation. Yet there
are cases which are rare but represent important entities to be considered
in routine surgical pathology practice e.g. an interesting proliferation
of spindle cells within breast ducts.
QAP Symposium
Thursday 14 October
Morning Session
This session will show case quality assurance programs in Anatomical Pathology
from the United Kingdom, United States of America, Japan and Australia.
The speakers will present their current programs and future directions
of this important area of Pathology. These will highlight best practices
that can be taken home and readily used.
Afternoon Session - Error and Error Reduction Symposium
Errors in Anatomical Pathology is an issue that is gaining increasing
recognition and concern within our profession. In this session speakers
will discuss the types of errors that can occur in Anatomical Pathology
and recommend useful ways to recognize and reduce them. The presentations
and illustrative cases will emphasize the importance of using, monitoring
and maintaining quality systems to minimize the errors and continue to
improve the practice of anatomic pathology and the outcomes of patients.
The Autopsy in Modern Society: a Precarious Relationship.
Friday Afternoon
Eight speakers from around the world will discuss the benefits of the
autopsy, as well as the difficulties the autopsy is facing (such as retained
organ issues). If the autopsy is to survive, we must advocate it as one
of the best tools for teaching medical students, and look at ways of integrating
it with other patient investigations to act as a total quality tool. Ways
of improving the performance and reporting of autopsies will be discussed.
Lateral thinking will also be encouraged by way of consideration of veterinary
autopsies, and the complex medicolegal autopsy.
Photography
Friday Morning
This is a “hands on” demonstration of photomicrography and
gross specimen photography using digital technology presented by professional
medical photographers. Filing of these images, and converting them to
power point for a presentation will be demonstrated. Preparation of digital
images for printing will be demonstrated. This is an opportunity for pathologists
to ask advice from experts.
Veterinary Pathology Session
On Friday afternoon the Veterinary Pathology session will present in detail
the veterinary version of the interesting panel of zoonotic diseases which
have emerged recently in Australia and nearby regions in Asia. These conditions
include SARS, Hendravirus, Nipavirus and Australian bat lyssavirus, with
probable passing mention of avian influenza H5. This session will complement
the infectious diseases session to be held on Friday morning.
Lung Tumour Slide Seminar
This slide seminar will showcase eight distinct and, at times, unusual
tumours as presented by pathologists experienced in lung diseases including
Bill Travis, Tom Colby and Elisabeth Brambilla. These tumours encompass
benign and malignant and primary and metastatic lesions.
Interstitial Lung Diseases Slide Seminar
The recent American Thoracic Society/European Respiratory Society classification
highlights the need for clinical, radiological and pathological correlation
in proper diagnosis of interstitial lung diseases. This slide seminar,
as presented by some of the leading lights of pulmonary pathology, endeavours
to take common and unusual interstitial lung diseases and demonstrate
an approach to their diagnosis.
Sudden Cardiac Death Symposium
Sudden cardiac death is a common mode of death which has many underlying
aetiologies. This symposium includes presentations by Dr Allen Burke and
Dr Eugene Mark who will discuss common forms of death including coronary
artery disease and myocardial abnormalities as well as more unusual modes
such as death related to pulmonary embolus, electrophysiological abnormalities,
particularly long QT segment and valvular disease.
Symposium on Diseases of Blood Vessels
Every organ has blood vessels. Therefore, an understanding of disease
processes associated with blood vessels is essential to every working
pathologist. This symposium will cover the gamut of pathological processes
associated with blood vessels including large vessel and small vessel
inflammatory and neoplastic disorders. Speakers from Asia, North America
and Australia expert in the field will present their experience with these
processes.
Back
to top |
CISH Testing for HER2 and Correlation with IHC and FISH:
The Results of an Australian Study.
Associate Professor Michael Bilous, Director,
Department of Tissue Pathology, Institute of Clinical Pathology and Medical
Research, Westmead Hospital, NSW.
|
ADVERTISEMENT
Introduction
Patients with metastatic breast cancer whose tumours
overexpress HER2 and/or show amplification of the HER2 gene show significant
survival advantage after treatment with Herceptin®. HER2 testing of
breast cancer specimens is therefore being performed in laboratories throughout
the world.
The two main testing methods in general use and globally accepted as the
HER2 testing standard methodologies are immunohistochemistry (IHC) to
detect HER2 protein overexpression and fluorescence in-situ hybridisation
(FISH) to detect amplification of the HER2 gene. Both methodologies are
specific and reliable. However, they also have their problems.
Chromogenic in-situ hybridisation (CISH) has recently
been adapted for the detection of HER2 gene amplification and follows
the same principle as FISH. However, the CISH detection method involves
the DAB chromogen rather than a fluorescent marker, therefore only a normal
light microscope is required to visualise the result. Tumour cell morphology
is better seen and the resulting slides can be stored at room temperature
without loss of signal. CISH is therefore a potential alternative testing
method to FISH.
In order to evaluate the accuracy, ease of use and reproducibility of
CISH performed in different pathology laboratories, five Australian Laboratories
recently completed a study in which they compared the results of testing
for HER2 using CISH on a series of breast cancers for which the HER2 status
was known by IHC and FISH. The results of this study were the subject
of a poster and presentation at the European Breast Cancer Conference
held in Hamburg in March 20041. Three of the five laboratories had no
previous experience in the use of CISH. These laboratories received 2
days CISH training prior to participation in the study. A summary of the
results of the study is given below.
Materials and Methods
Sections of 50 breast cancers labelled A1–50 were each tested for
HER2 in two different laboratories using CISH with SpoT-Light® HER2
DNA probe (Zymed Laboratories Inc). Each of the five participating laboratories
thus tested 20 of the cancers.
Each cancer had been previously tested for HER2 using IHC; the HercepTest®
(Dako Cytomation) had been used in the majority of cases. All the cancers
had scored either 2+ (equivocal) or 3+ (positive) using the HercepTest®
scoring system.
Each cancer had also been previously tested for HER2 gene amplification
by FISH using PathVysion® (Vysis, Abbott) at one central laboratory
(St Vincent’s Hospital, Sydney, Australia). The results of both
CISH and FISH were expressed as no amplification, low amplification or
high amplification of the HER2 gene.
The laboratories taking part in the study did not know the previous HER2
results of the cancers being assessed by CISH
Scoring system
CISH was scored as follows:
• 1–5 HER2 signals per nucleus = no amplification of the gene
• 6–10 signals or a small signal cluster = low amplification
• >10 signals or large clusters = high amplification.
Results
Morphology in the CISH stained sections
Preservation of cellular morphology in the sections was assessed as reasonable,
good or excellent in 42 of the 50 cases (84%)
Repeat staining was required in only five of the 50 cases (10%); the other
45 were assessable after the first staining run.
Comparison between FISH and CISH
Table 1 shows the correlation between CISH and FISH for the 50 cancers
in
duplicate set 1.
• No cases showing high gene amplification by FISH (21 cases) were
considered non-amplified by CISH (kappa coefficient = 1)
• Of the 31 cases showing low and high amplification by FISH, 28
cases also showed amplification by CISH (kappa coefficient = 0.88)
• Correlation between CISH and FISH for low- and high-amplification
cases was moderate (kappa coefficient = 0.5).
Table 1
Correlation between CISH and FISH.

Comparison between CISH & IHC
Table 2 shows the comparison between CISH and IHC results
• All cases scored 2+ or 3+ by IHC as part of the selection criteria
• All cases scored as 3+ by IHC showed gene amplification by CISH
• Of 31 cases giving a 2+ result by IHC, 22 (70%) did not show amplification
by CISH.
• Of the 22 cases showing high gene amplification by CISH, 16 (72%)
had scored 3+ by IHC
Table 2
Correlation between CISH and IHC

Correlation between CISH performed on
the same cases in two different laboratories
Table 3 shows the inter-laboratory CISH correlation.
• The kappa coefficient was 0.67, indicating good strength of agreement
between the two complete sets of results
• In the two sets of results there were no discordant cases when
comparing high level gene amplification with no gene amplification (Kappa
coefficient = 1).
• A comparison of both high- and low-level amplified versus non-amplified
cases shows very good strength of agreement (Kappa coefficient = 0.83)
• In those cases assessed as non-amplified in one set of results
and low-level amplified in the other, the number of signals counted in
the same case varied markedly. For example Case A48: 1.4 and 8.6, Case
A10: 3.96 and 1.8; Case 47: 3.2 and 6.
Table 3
Inter-laboratory CISH correlation.

Discussion
There is excellent correlation between CISH and FISH for identifying high-level
HER2 gene amplified breast cancers, and good correlation in assessing
any amplification using the manufacturer’s interpretation of results
for both techniques. Given the different criteria for assessing high-
and low-level gene amplification in the FISH and CISH techniques, it was
predictable that the low gene amplification category would present the
greatest number of discrepant cases.
There is very good correlation between the results obtained by laboratories
performing CISH on the same cases, even when the laboratories have little
or no previous experience with the technique.
CISH showed a strong correlation with HercepTest® IHC, in the majority
of cases.
Laboratories performing CISH for the first time experienced very little
difficulty in using the technique and in interpreting the results. Comment
was however made concerning the difficulty in counting the precise number
of signals present in coarse clusters seen in the nuclei of some cancer
cells. These are most likely to be highly amplified cases.
This study also showed ( data not shown) that more than 50% of cases showing
HER2 gene amplification were ER positive but that the proportion of ER-positive
cells was less in those cancers showing high-level HER2 gene amplification
than in those with low-level or no amplification. Testing for HER2 should
therefore not be restricted to those cancers that are ER negative.
The clinical significance of low-level HER2 gene amplification with CISH
(6–10 copies of the HER2 gene signal per nucleus) or FISH (HER2
gene:chromosome 17 ratio of 2–4) will need to be clarified in the
light of treatment outcome data.
Conclusions
CISH testing for HER2 gene amplification represents a potential alternative
method to FISH.
CISH can be performed by pathology laboratories without prior CISH experience
with minimal training.
Results obtained using CISH are highly reproducible between laboratories.
Reference
1. Bilous M., Morey A., Armes J., Cummings M., Francis G. Abstract
and Poster No. 160; 4th European Breast Cancer Conference, March 16-19
2004
Back to top
|