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

69
Id2 expression is inversely correlated with tumour grade in
breast cancer
JP Bury , SS Cross , S Balasubramanian , MW Reed , CE Lewis
University of Sheffield, Sheffield, United Kingdom
Id proteins are members of the basic-Helix-Loop-Helix (bHLH) family of
transcription factors. The four known members of the family (Id1, Id2, Id3 and
Id4) lack a DNA binding domain, and function as dominant negative regulators
of DNA transcription by other bHLH transcription factors, with which they
heterodimerise and thus inactive. Id2 expression has been shown to be required
for the maintenance of a differentiated phenotype in breast epithelial cells. In
this study we sought to compare levels of Id2 expression in breast tumours, as
assessed immunohistochemically, with tumour grade. 3 triplicate tissue
microarrays were created, each containing 170 1mm diameter cores, one from
each of 170 breast cancers. These arrays were immunostained using a
polyclonal antibody against Id2 (Santa Cruz sc-489). Specificity of staining was
demonstrated using a specific peptide blocker, which blocked all staining. Each
core was assigned a score of 0 or 1 on the basis of the presence or absence of
Id2 staining. A composite score was calculated for each tumour by adding
together the scores for tissue cores from the same tumour in each of the three
microarrays. The mean total score was 1.81 for grade 1 tumours (n=36), 1.68
for grade 2 tumours (n=79) and 1.05 for grade 3 tumours (n=55). This decrease
in Id2 expression with increasing tumour grade was statistically significant
(p=0.005, Kruskal Wallis test). To our knowledge, this is the largest series of
breast tumours in which Id2 expression has been correlated with tumour
differentiation, and a clear association between tumour de-differentiation and
loss of Id2 expression is demonstrated. Studies of the prognostic significance
of Id2 expression in breast carcinoma may be valuable.
70
Should random quadrant samples be taken when assessing a
cancer mastectomy specimen?
CDT Bratten , P Carder , S Lane , A Hanby
Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
When assessing a mastectomy specimen, pathologists take great care to
accurately locate and extensively sample all macroscopic or radiologically
detected lesions. In addition, it is common practice to randomly sample each of
the four quadrants.
The utility of so doing has only been studied once (Gupta-Dilip et al., 2003,
Breast J., 9(4), 307-11). In this US study of 78 mastectomy specimens the
authors concluded that random quadrant sampling added clinically useful
information in a high proportion of cases (27%). The relatively high number of
‘random’ blocks taken (mean 9, range 2 to 19), and the high percentage of cases
with positive quadrant findings, lead us to believe that this study might not be
representative of our experience, where traditionally only two to four random
blocks are taken and positive findings were thought to be less frequent.
Accordingly, we reviewed all mastectomy specimens over a two year period
(2001-2002) received by our hospital. In total 388 reports were examined; in 47
cases (12%), random quadrant blocks were positive for malignant disease (17
in-situ disease, 22 invasive, 8 lymphovascular permeation). In all of these cases
these features had been noted in the main tumour blocks. There was no
association with invasive tumour type and positive quadrant findings.
However, there were 14 cases (3%) where the random findings were the only
indication of disease potentially more widespread than the main tumour blocks
(i.e. all nodes negative and lymphovascular invasion not seen). 10 of these
cases identified further in-situ disease and 4 cases invasive disease in the
random quadrants. Nevertheless, the clinical impact these extra findings had on
patient management is debatable.
71
Audit Of C3 And C4 Breast Fine Needle Aspirate Cases With
Histological Correlation
I U Nicklaus-Wollenteit , N Singh , RJ Howitt
Southampton University Hospitals NHS Trust, Department of Cellular
Pathology, Southampton, United Kingdom
All fine needle aspirates of the breast reported as C3 “atypia probably benign“
or C4 “suspicious of malignancy“ during 2002 in a large university teaching
hospital department have been audited with regard to frequency and histological
outcome. In total 982 cases were reported by one of four cytopathologists
according to the NHSBSP guidelines for cytology.
74 cases (7.5%) were reported as C3 of which 61 proceeded to biopsy, and 42
cases (4.3%) were reported as C4 of which 41 had a histological diagnosis. 18
of the 61 C3 cases (29.5%) were malignant on subsequent histology: 4 low or
intermediate grade DCIS; 11 grade 1 or 2 invasive carcinomas, including
lobular, mucinous and adenoid cystic subtypes; and 3 invasive grade 3
carcinomas.
Of the 42 C4 cases 31 were confirmed as histologically malignant (73.8%): 25
grade 1 or 2 invasive carcinomas; 4 grade 3 invasive carcinomas; and 2 cases of
pure DCIS. Fibroadenomas and epithelial hyperplasia accounted for a high
proportion of benign lesions reported as C4.
Comparison with a previous study shows similar results. The C3 and C4
categories have distinct histological counterparts, and when used appropriately
allow the classification of challenging cases into clinically distinct groups with
different likelihood of malignancy.
72
The Retrospective Reconstruction Of Prognosis In Breast
Cancer: The Use Of The Nottingham Prognostic Index In The
Medico-Legal Arena.
C Elston 1 , M Blamey 1 , NA Wright 2
1 Department of Histopathology, City Hospital, Nottingham, United
Kingdom, 2 Histopathology Unit, Cancer Research (UK), London, United
Kingdom
INTRODUCTION: The Nottingham Prognostic Index (NPI) is well-established
in comparative use in clinical trials and for assessing prospective prognosis.
Here we assess both its application and success in the retrospective
determination of prognosis in cases of litigation for delayed diagnosis of breast
cancer. METHODS: the usual request is to reconstruct the prognosis of a case
of breast cancer if diagnosis and treatment had occurred at some time
previously, which varies between cases. The usually available data are (i) the
diameter of the tumour at resection; (ii) the grade of the tumour at resection and
(iii) the nodal status after axillary sampling or clearance. Using published data
for the doubling time of breast carcinomas, the diameter of the tumour at the
time in question can usually be calculated within confidence intervals.
Published data relating the size of the tumour to the probability of nodal
metastases can be used to assess nodal status at this time for unit grade of
tumour. The NPI can then be calculated for the time(s) of alleged misdiagnosis.
RESULTS: In many cases, the dataset is sufficient to provide values for the NPI
and thus survival probability, and in a considerable number of cases the NPI has
been accepted by the Court since the index case of Judge v Quick, which we
believe was the first to show causation in an alleged case of missed breast
cancer. The success of this approach can be assessed now from a dataset
which includes several hundred cases. Problems which have been encountered
include cases where (a) the diameter of the diameter at diagnosis/excision
cannot be assessed; (b) the nodal status is unknown and (c) where there are
metachronous tumours. Areas where disputes in expert evidence arose
included disagreements about the growth rate of breast carcinoma and the
significance of the size of nodal and systemic metastases. CONCLUSION: the
NPI has found an unlooked for niche within the medico-legal field which makes
it very valuable so long as the assumptions and constraints implicit in the
method are remembered.
44