We thank the reader for the careful and critical evaluation of our publication “Value of multicolor Fluorescence in situ Hybridization (UroVysionTM) in the differential diagnosis of flat urothelial lesions”
published by Stephan Schwarz, Michael Rechenmacher, Tomas Filbeck, Ruth Knuechel, Hagen Blaszyk, Arndt Hartmann and Gero Brockhoff. The reader realized some inconsistency in the Material and Methods section of our paper r...
We thank the reader for the careful and critical evaluation of our publication “Value of multicolor Fluorescence in situ Hybridization (UroVysionTM) in the differential diagnosis of flat urothelial lesions”
published by Stephan Schwarz, Michael Rechenmacher, Tomas Filbeck, Ruth Knuechel, Hagen Blaszyk, Arndt Hartmann and Gero Brockhoff. The reader realized some inconsistency in the Material and Methods section of our paper regarding HER2 immunohistochemistry (IH). In our lab for some
purposes a manual IH procedure is performed, for others we execute an automated one. In fact for the study published by Schwarz et al. we used a combination of both: section preparation was done manually and the subsequent staining procedure was performed on the NexES immunostainer
(Ventana Medical Systems, Tucson, Arizona, USA). However, we agree with the reader that we produced some inconsistency and incorrectnesses in the
Material & Methods. Hence we would like to provide this amended description of immunohistochemical HER2 staining and interpretation as follows:
“HER2 immunostaining was done on 2 mm sections using a HER2 antibody (CB11 CB11-Pathway, prediluted, FDA approved, Ventana Medical Systems, Tucson, Arizona, USA). Before staining, the tissue slides were deparaffinised and
rehydrated at room temperature. For antigen retrieval the sections were immersed in 10 mmol/l citrate buffer and microwaved for 30 min using 300 Watt (no pressure cooker was used). Subsequently the sections were cooled
by rinsing water for a couple of minutes. Then an automated staining protocol on the NexES immunostainer (Ventana Medical Systems, Tucson, Arizona, USA) was performed featuring some slight modifications with respect to the recommendation given by Ventana
(http://www.ventanamed.com/msds/files/14160USb2.pdf). The protocol described here numerously proved to work reliably on the NexES immunostainer. After a 30-minute incubation at 37°C with the primary antibody, sections were incubated for another 10 minutes at 37°C with a secondary biotinylated antibody and then with avidin-peroxidase for another 10 minutes; 3',3-diaminobenzidine was used as the chromogen. All products needed for these steps are included in the DAB detection kit provided by the manufacturer (Ventana Medical Systems, Tucson, Arizona, USA). Slides were haematoxylin counterstained, dehydrated, and mounted. A multiblock control consisting of four cell lines representing different staining intensities ranging from 0 to 3+ (MDA-MB-231: Score 0, MDA-MB-175: Score 1+, MDA-MB-453: Score 2+, and SK-BR-3: Score 3+) served as controls for all specimens.
Again we would like to thank for the careful reading of our manuscript and for coming up with the letter to the editor. This procedure assures appropriate publication quality of JCP.
Dear Editor
In the section Methods the authors described Immunohistochemistry of HER2. The described protocol is an inconsistent mixture of a manual and automated immunostaining procedure and it is very unlikely that it was actually applied.
In a second sentence the authors stated that “a manual avidin-biotin peroxidase complex procedure was used in the immunohistochemical analysis according to the ma...
Dear Editor
In the section Methods the authors described Immunohistochemistry of HER2. The described protocol is an inconsistent mixture of a manual and automated immunostaining procedure and it is very unlikely that it was actually applied.
In a second sentence the authors stated that “a manual avidin-biotin peroxidase complex procedure was used in the immunohistochemical analysis according to the manufacturer’s recommendations”. The HER 2 antibody,
CB11 from Ventana Medical Systems used in this study is recommended for staining on Ventana automated immunostainers with Ventana detection kit
and not for manual staining with other detection systems
(http://www.ventanamed.com/msds/files/14160USb2.pdf). However, if they really used the manual staining, the information about the applied detection system and the validation study reference is missing.
In contradiction with the statement in second sentence, in the fifth sentence the authors stated that “an automated staining on the Nexus (Ventana Medical Systems, Illkirch, France) was performed”. Moreover Ventana Medical Systems automated immunostainer is Nexes and not Nexus.
In the fourth sentence they stated that”the sections were microwaved in a pressure cooker” which is obvious incompatible.
In the sixth sentence they continued describing the manual immunostaining protocol – after staining (on the Nexes) they stain the sections again!
It is very interesting that many readers (authors, reviewers) overlooked such inconsistently described procedure.
We read with interest the article by K. Swe Swe and coauthors (1),
which enriches our knowledge about non-typhoidal salmonella meningitis.
From our own experience, we know that there are unexpected difficulties in
addressing some aspects of this rare disease, which may result in
inaccuracies. The authors stated that 10 out of total 17 cases of this
rare infection have been reported in adults lacking po...
We read with interest the article by K. Swe Swe and coauthors (1),
which enriches our knowledge about non-typhoidal salmonella meningitis.
From our own experience, we know that there are unexpected difficulties in
addressing some aspects of this rare disease, which may result in
inaccuracies. The authors stated that 10 out of total 17 cases of this
rare infection have been reported in adults lacking positive HIV status.
Back in 1984, using the English literature of pre-HIV era, Hardy and
coauthors also counted 10 reports of adult patients with non-typhoidal
salmonella meningitis (2). This was an underestimation due to inaccuracy
in the account of Kaufmann and St. Hilaire (3), upon which the authors of
both above mentioned papers drew their conclusions. Since 1984 the
collection of articles about this condition in English has grown and some
of them are cited by Carr and coworkers (4). In addition, more than 10
cases of meningitis caused by Salmonellae in adults have been reported in
Spanish and French (5, 6). Currently, the approximate number of cases
described in the medical literature appears to be at least twice that
provided by the authors. Further, the list of published Salmonella
typhimurium meningitis reports in adults, which the authors limited to 3,
is also longer (7, 8, 9).
We have stressed previously that accounts regarding recorded salmonella
meningitis cases in some frequently cited sources are incorrect (10). When
it comes to the description of rare diseases, comprehensive analysis of
literature, including older and non-English articles, can add
substantially to the accuracy of publication.
Yuri Zagvazdin, Ia Zagvazdina
REFERENCES:
1. Swe KS, Nagel G, Van der Westhuizen M, et al. Salmonella typhimurium
meningitis in an adult patient with AIDS. J Clin Pathol 2008; 61:138-9.
2. Hardy C, Bansal A, Lowes JA, et al. Salmonella meningitis following
treatment of enteritis with neomycin. Postgrad Med J 1984; 60: 284-6.
3. Kauffman CA, St Hilaire RJ. Salmonella meningitis. Occurrence in an
adult. Arch Neurol 1979; 36: 578-80.
4. Carr BG, Weisbein JL, Gaieski DF. Salmonella meningitis in an
immunocompetent adult. J Emerg Med 2008 (In press)
5. Tena D, Pérez Pomata MT, Gimeno C, et al. Salmonella sp. meningitis in
the adult. Case report and review of the Spanish literature. Enferm Infecc
Microbiol Clin 2001; 19: 238-40.
6. Aissaoui Y, Azendour H, Balkhi H, et al. Postoperative meningitis
caused by an unusual etiological agent: Salmonella enteritidis.
Neurochirurgie 2006; 52: 547-50.
7. Spieckermann D, Lütticken R, Goertz B. Salmonella meningitis in adults:
a case of Salmonella typhimurium infection. Infection 1973; 1: 178-80.
8. Korchinskaia TA. Meningeal lesions in salmonellosis. Vrach Delo 1975;
12:126-7.
9. Chhina RS, Gupta BK, Wander GS, et al. Chloramphenicol resistant
Salmonella meningitis in adults--a report of 3 cases. J Assoc Physicians
India 1993; 41: 535.
10. Zagvazdina Ia, Zagvazdin Y, Willis GE, et al. Rare infections are just
an airplane trip away: Salmonella typhi meningitis in a recent immigrant
to the United States. Am J Med Sci 2005; 330: 198-200.
I fully endorse the recommendations of Reddy and co-workers
concerning management of potential Brucella isolates and those staff
potentially exposed 1. The authors highlight that clinical information may
not always suggest potential brucellosis, especially if time has elapsed
since exposure, thus suspicion may not be raised. The authors then proceed
to describe four blood culture isolates obtained from patien...
I fully endorse the recommendations of Reddy and co-workers
concerning management of potential Brucella isolates and those staff
potentially exposed 1. The authors highlight that clinical information may
not always suggest potential brucellosis, especially if time has elapsed
since exposure, thus suspicion may not be raised. The authors then proceed
to describe four blood culture isolates obtained from patients with travel
histories to endemic regions. Although recovery of Brucella from blood
cultures taken from patients with undulant fever is the typical text book
scenario, readers should be aware that brucellae may result in focal
lesions affecting nearly every organ 2. Unusual sources for isolation of
brucellae are typified by the recent recovery of a Brucella-like organism
from a breast implant 3.
The importance of non-blood samples for diagnosis of brucellosis must
also be stressed. Where there is a suitable degree of clinical suspicion,
bone marrow is the sample of choice for isolation. This is further
substantiated by the recent findings of Mantur and co-workers who
undertook a comparative study of Brucella recovery from various specimens.
During these investigations, recovery was only achieved from 45.6% of
blood cultures whereas 82.5% of bone marrow biopsies yielded growth 4.
Although the United Kingdom is officially Brucella-free, I would like to draw the attention of medical colleagues to
recent human infections with marine mammal-associated brucellae. A paper
by Sohn et al described two patients with neurological disease attributed
to infection with strains of Brucella derived from marine mammals 5.
Brucella was isolated following surgical intervention although only one
patient was positive serologically. A further infection initially
mistaken as B. suis, was reported from New Zealand 6. Previously,
laboratory-acquired infection with a similar strain had been described 7.
Serological and cultural evidence suggests that brucellosis is very
widespread in a range of cetaceans, pinipeds around the coasts of the
British Isles and elsewhere, and there is similar evidence that otters
located inland are also infected 8.
Finally, regarding the application of PCR to identify Brucella in
clinical material as used in case 4, this provides a useful diagnostic
tool, negating the need to handle large quantities of this highly
infectious microbe. Indeed, this has proven particularly valuable to
confirm infection in patients, and household contacts with potential
shared exposures 9. Molecular diagnostics have now evolved to offer
equivalent discriminatory power to more traditional identification
methods, however, cultivation and classical microbiological biotyping
remain the gold standard, underscoring the need for precise
recommendations for reduction of laboratory exposure, or appropriate
management of exposed individuals, as outlined in the afore mentioned
article.
Sally J Cutler
References:
1.Reddy S, Manuel R, Sheridan E, et al., Brucellosis in United
Kingdom - a risk to laboratory workers? Recommendations for prevention and
management of laboratory exposure. Journal of Clinical Pathology,
2008:jcp.2007.053108.
2.Al Dahouk S, Nockler K, Hensel A, et al., Human brucellosis in a
nonendemic country: a report from Germany, 2002 and 2003. Eur J Clin
Microbiol Infect Dis, 2005;24:450-6.
3.De BK, Stauffer L, Koylass MS, et al., Novel Brucella Strain (BO1)
Associated with a Prosthetic Breast Implant Infection. Journal of Clinical
Microbiolology 2008;46:43-49.
4.Mantur BG, Mulimani MS, Bidari LH, et al., Bacteremia is as
unpredictable as clinical manifestations in human brucellosis. Int J
Infect Dis, 2008;12:303-7.
5.Sohn AH, Probert WS, Glaser CA, et al., Human neurobrucellosis with
intracerebral granuloma caused by a marine mammal Brucella spp. Emerging
Infectious Diseases, 2003;9:485-488.
6.McDonald WL, Jamaludin R, Mackereth G, et al., Characterization of a
Brucella sp. Strain as a Marine-Mammal Type despite Isolation from a
Patient with Spinal Osteomyelitis in New Zealand. Journal of Clinical
Microbiolology, 2006;44:4363-4370.
7.Brew SD, Perrett LL, Stack JA, et al., Human exposure to Brucella
recovered from a sea mammal. Veterinary Record, 1999;144:483.
8.Foster G, MacMillan AP, Godfroid J, et al., A review of Brucella sp.
infection of sea mammals with particular emphasis on isolates from
Scotland. Vet Microbiol, 2002;90:563-80.
9.Mendoza-Nunez M, Mulder M, Franco MP, et al., Brucellosis in Household
Members of Brucella Patients Residing in a Large Urban Setting in Peru. Am
J Trop Med Hyg, 2008;78:595-598.
I was interested to read the article by Zheng and colleagues in the
July 2007 edition of the Journal of Clinical Pathology 1, wherein the
authors describe detection of Jamestown Canyon virus in human tissue
samples. I write to urge caution as I fear that a simple unfortunate error
has been made.
Jamestown Canyon virus is a bunyavirus belonging to the ‘California
serogroup’, an enveloped, sing...
I was interested to read the article by Zheng and colleagues in the
July 2007 edition of the Journal of Clinical Pathology 1, wherein the
authors describe detection of Jamestown Canyon virus in human tissue
samples. I write to urge caution as I fear that a simple unfortunate error
has been made.
Jamestown Canyon virus is a bunyavirus belonging to the ‘California
serogroup’, an enveloped, single stranded RNA virus. It is an arthropod-
borne virus found predominantly in northern America 2,3. It is not, as
Zheng et al suggest, “a family of polyoma viruses”. I suspect that the
authors have confused this virus (often abbreviated to JCV) with the more
widely known JC polyomavirus, which is named for the initials of a patient
suffering from progressive multifocal leukoencephalopathy 4. Indeed, the
article seems to describe JC polyomavirus throughout rather than Jamestown
Canyon virus.
In order to avoid ongoing confusion, I would suggest that the article
be withdrawn and republished with suitable amendments.
James J Clayton
References
1. Zheng H, Murai Y, Hong M, Nakanishi Y, Nomoto K, Masuda S,
Tsuneyama K, Takano Y. Jamestown Canyon virus detection in human tissue
specimens. J Clin Pathol. 2007; 60:787-93.
2. Grimstad PR, Shabino CL, Calisher CH, Waldman RJ. A case of
encephalitis in a human associated with a serologic rise to Jamestown
Canyon virus. Am J Trop Med Hyg. 1982; 31:1238-44.
3. Mayo D, Karabatsos N, Scarano FJ, Brennan T, Buck D, Fiorentino T,
Mennone J, Tran S. Jamestown Canyon virus: seroprevalence in Connecticut.
Emerg Infect Dis. 2001; 7:911-2.
4. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH.
Cultivation of papova-like virus from human brain with progressive
multifocal leucoencephalopathy. Lancet. 1971; 1(7712):1257-60.
In the context of clinically suspected non-thyroidal illness(NTI) the
advice to retest patients with raised levels of thyroid stimulating
hormone(TSH)(1) may extend even to those in whom TSH levels are in the
range 20-32.4 mIU/L(2). In one study, over a period averaging 88
days(Standard Error ie SE=34), seven such subjects, with mean baseline TSH
of 32.4 mIU/L(SE=3.6), experienced a spontaneous fall in...
In the context of clinically suspected non-thyroidal illness(NTI) the
advice to retest patients with raised levels of thyroid stimulating
hormone(TSH)(1) may extend even to those in whom TSH levels are in the
range 20-32.4 mIU/L(2). In one study, over a period averaging 88
days(Standard Error ie SE=34), seven such subjects, with mean baseline TSH
of 32.4 mIU/L(SE=3.6), experienced a spontaneous fall in that parameter to
levels averaging 12.3 mIU/L(SE=3.7)as a result of recovery from NTI. In
two of those subjects, both of whom tested negative for antimicrosomal
antibodies, TSH fell to 2.1 mIU/L, and 2.3 mIU/L, respectively. In the
other five, all of whom were antibody positive, TSH levels fell to 9.9,
10.1, 11.5, 21.7, and 28.5 mIU/L,respectively. In order to check whether
or not patients tested for TSH have significant but clinically unsuspected
NTI it might even be advisable to test for the acute phase marker, C
reactive protein(CRP). This was the strategy followed in one study so as
to check if patients with suspected hypoferritinaemia might have spurious
"normalisation" of their serum ferrtin levels attributable to an acute
phase response. In that study 10.2% and 44% of patients in primary care
and in secondary care, respectively, had elevated CRP levels(3). Where
necessary, TSH levels also need to be interpreted in the context of
advanced age, given the recent analysis of the age-specific distribution
of TSH levels in 14,376 subjects who were not only disease-free, but also
tested negative for thyroid antibodies. In that analysis the 95%
confidence limits for TSH yielded the range 6.17-10.85 mIU/L in patients
aged 80 or more(4). One interpretation of these findings was that the age-
related shift in the reference range "could either facilitate or be a
consequence of healthy aging"(4). This view resonated with the findings in
a cohort of 599 subjects 37 of whom had overt hypothyroidism, the latter
characterised by the association of subnormal levels of free thyroxine and
TSH levels in the range 4.86-33.0 mIU/L. The enrollment age was 85, and
the mean follow up was 3.7 years(standard deviation 1.4). Over that
period, in spite of non-treatment, these overtly hypothyroid participants
showed a significant trend towards the lowest mortality rates when
compared with the rest of the cohort(Cox regression, P for trend=0.03).
Furthermore, increasing baseline levels of TSH were not associated with an
accelerated increase in phsical disability, cognitive decline, or
depressive symptoms(5). Accordingly, in primary care best practice is to
take account of NTI, using clinical criteria, and, possibly, CRP as well,
and to take cognisance of advanced age.
Oscar M Jolobe Retired Geriatrician
References
(1) Smellie WSA., Vanderpump MPJ., Fraser WD., Bowley R., Shaw N
Best Practice in primary care pathology; review 11
Journal of Clinical Pathology 2008:61:410-18
(2)Spencer C ., Elgen A., Shen D et al
Specificity of sensitive assays of thyrotropin(TSH) used to screen for
thyroid disease in hoispitalised patients
Clinical Chemistry 1987:33:1391-6
(3) O'Broin S., Kelleher B., Balfe A., mCMahon C
Evaluation of serum transferrin receptor assays in a centralised iron
screening service
Clinical and Laboratory Haematology 2005:27:190-4
(4) Surks MI., Hollowell JG
Age-specific distribution of serum thyrotropin and antithyroid antibodies
in the U.S. population: Implications for the prevalence of subclinical
hypothyroidism
Journal of Clinical Endocrinology and Metabolism 2007:92:4575-82
(5) Gussekloo J., van Exel E., de Craen AJM et al
Throid status, disability and cognitive function, and survival in old age
Journal of the American Medical association 2004:292:2591-9
Letter to the Editor - Sputum sampling, storage and recovery: accuracy and sensitivity for Mycobacterium tuberculosis
Dear Editor,
The recent article by Pye et al. discusses the recovery of bacteria
from sputum specimen samples stored at different temperatures (1). This
article highlights sample handling, storage and transport, from the field
to the clinical laboratory. This may be important in the fiel...
Letter to the Editor - Sputum sampling, storage and recovery: accuracy and sensitivity for Mycobacterium tuberculosis
Dear Editor,
The recent article by Pye et al. discusses the recovery of bacteria
from sputum specimen samples stored at different temperatures (1). This
article highlights sample handling, storage and transport, from the field
to the clinical laboratory. This may be important in the field collection
and identification of highly contagious and epidemiologically important
microbes like Mycobacterium tuberculosis (MTB). Indeed, Tansuphasiri et
al. found that positive cultures of MTB decreased significantly when
stored at room temperature for 5 days compared with cultures from fresh
specimens (2). Conversely, storage of MTB at low temperatures (-20 0C) for
2 months also increased bacterial lysis and decreased recovery (3). To
date, research supports the use of molecular methods (e.g. polymerase
chain reaction) the sensitive detection of small sample sizes of sputum
collection bacterial (i.e. MTB) (4), and the shipping of sampling from
rural, isolated areas for accurate molecular diagnosis is preferred
methodology over sputum smears (5).
Kenneth Hoekstra Assistant Professor
Western States Chiropractic College
References
1. A Pye, S L Hill, P Bharadwa, and R A Stockley Effect of storage
and postage on recovery and quantitation of bacteria in sputum samples J
Clin Pathol 2008; 61: 352-354
2. Tansuphasiri U, Chinrat B, Rienthong S.Evaluation of culture and
PCR-based assay for detection of Mycobacterium tuberculosis from sputum
collected and stored on filter paper. Southeast Asian J Trop Med Public
Health. 2001 Dec;32(4):844-55.
3. Pathak D, Chakravorty S, Hanif M, Tyagi JS. Lysis of tubercle
bacilli in fresh and stored sputum specimens: implications for diagnosing
tuberculosis in stored and paucibacillary specimens by PCR. BMC Microbiol.
2007 Sep 4;7:83.
4. Guio H, Okayama H, Ashino Y, Saitoh H, Xiao P, Miki M, Yoshihara
N, Nakanowatari S, Hattori T.
Method for efficient storage and transportation of sputum specimens for
molecular testing of tuberculosis.
Int J Tuberc Lung Dis. 2006 Aug;10(8):906-10.
5. Tansuphasiri U, Boonrat P, Rienthong S.Direct identification of
Mycobacterium tuberculosis from sputum on Ziehl-Neelsen acid fast stained
slides by use of silica-based filter combined with polymerase chain
reaction assay. J Med Assoc Thai. 2004 Feb;87(2):180-9.
We read with interest the paper by Borgquist et al (2008),
published recently in Journal of Clinical Pathology1. In their article
the authors aimed to investigate the impact of ERbeta expression on breast
cancer outcome using a cohort of 512 tumours represented in tissue
microarray (TMA). Since the discovery of ERbeta over a decade ago, this
has been the goal of many research groups. However pr...
We read with interest the paper by Borgquist et al (2008),
published recently in Journal of Clinical Pathology1. In their article
the authors aimed to investigate the impact of ERbeta expression on breast
cancer outcome using a cohort of 512 tumours represented in tissue
microarray (TMA). Since the discovery of ERbeta over a decade ago, this
has been the goal of many research groups. However progress in this area
has been impeded by the lack of a consensus in terms of choice of primary
antibody and cut-off value used to determine ERbets postivity2,3.
Additionally, we know that ERbeta exists as 5 isoforms (ERbeta1-5), each
formed by alternative splicing of the last coding exon4,5, which has
further complicated interpretation of immunohistochemical studies.
Comparative studies have been conducted to help determine the most
suitable antibody for a number of applications and of these, 2 reliable
antibodies have emerged for immunohistochemistry: 14C8 (AbCam, Cambridge,
UK), located in the N-terminus of the ERbeta peptide and which detects
most isoforms of ERbeta and PPG5/10 (Serotec, Oxford, UK) which is
specific for ERbeta12,6,7. We routinely use both these antibodies in
our immunohistochemical studies. Borgquist et al1 used a different
antibody, EMR02 (Novocastra, Newcastle-upon-Tyne), which is claimed
through epitope mapping studies to show specific reactivity to a 17-amino
acid sequence present in the C-terminus of full length wild type ERbeta
and which is absent in ERbeta2/ERbetacx 8. While Borgquist et al1 show
immunohistochemical and Western blot analysis of ERbeta in a panel of
breast cell lines we find it remarkable that they showed no staining of
their breast TMAs especially as all the survival data presented in the
paper was obtained from these. Using cell lines to validate antibodies is
certainly a step in the right direction but it is insufficient as tissue
characteristics and processing protocols will almost certainly differ
substantially from those used in cell lines and these may alter antibody
specificity and sensitivity.
In addition, the authors used a very low cut off value to define
ERbeta positivity (1%) and with such a value we find it surprising that
the percentage of ERbeta positive tumours was only 50% - substantially
less than in many previous studies6,9-12. We believe this could
indicate an issue with antibody specificity and suggest this be confirmed
through peptide absorption studies.
Finally, as part of or on-going programme to understand the
significance of ERbeta in breast carcinogenesis, when EMR02 antibody
became available, we compared its efficacy to the well-validated 14C8 and
PPG5/10 antibodies which we use routinely. As illustrated in Figure 1, we
were unable to achieve robust and consistent staining using EMR02, while
TMA and full sections of breast carcinoma were clearly stained with 14C8
and PPG5/10.
Figure 1 - Serial sections of TMAs (top panel) and full sections (bottom panel) of breast carcinomas stained with EMR02 (a, d), 14C8 (b, e) and PPG5/10 (c, f). Consistent staining was only observed for 14C8 and PPG5/10 with EMR02 unable to detect the protein.
There still remains a great deal of controversy and indeed suspicion
surrounding the potential importance of ERbeta in breast cancer. We
believe to a large extent this is due to the use of poorly validated
antibodies which have poisoned the field somewhat. We urge all scientists,
clinicians and journals to be aware of the need for carefully validated
studies to help eliminate these controversies which, more than a decade
on, still continue to cloud ERbeta.
Valerie Speirs
References
1. Borgquist S, Holm C, Stendahl M, et al. Oestrogen receptors alpha and
beta show different associations to clinicopathological parameters and
their co-expression might predict a better response to endocrine treatment
in breast cancer. J Clin Pathol 2008;61:197-3.
2. Carder PJ, Murphy CE, Dervan P, et al. A multi-centre investigation
towards reaching a consensus on the immunohistochemical detection of
ERbeta in archival formalin-fixed paraffin embedded human breast tissue.
Breast Cancer Res Treat 2005;92:287-93.
3. Shaaban AM, Speirs V. Estrogen receptor beta - which one and where
should we draw the line? Hum Pathol 2006;37:498.
4. Moore JT, McKee DD, Slentz-Kesler K, et al. Cloning and
characterization of human estrogen receptor beta isoforms. Biochem Biophys
Res Commun 1998;247:75-8.
5. Poola I, Abraham J, Baldwin K, et al. Estrogen receptors beta4 and
beta5 are full length functionally distinct ERbeta isoforms: cloning from
human ovary and functional characterization. Endocrine 2005;27:227-38.
6. Skliris GP, Parkes AT, Limer JL, et al. Evaluation of seven oestrogen
receptor beta antibodies for immunohistochemistry, western blotting, and
flow cytometry in human breast tissue. J Pathol 2002;197:155-62.
7. Weitsman GE, Skliris G, Ung K, et al. Assessment of multiple different
estrogen receptor-beta antibodies for their ability to immunoprecipitate
under chromatin immunoprecipitation conditions. Breast Cancer Res Treat
2006;100:23-31.
8. Rees ML, Marshall I, McIntosh GG, et al. Wild-type estrogen receptor
beta expression in normal and neoplastic paraffin-embedded tissues. Hybrid
Hybridomics 2004;23:11-8.
9. Saunders PT, Millar MR, Williams K, et al. Expression of oestrogen
receptor beta (ERbeta1) protein in human breast cancer biopsies. Br J
Cancer 2002;86:250-6.
10. Shaaban AM, O'Neill PA, Davies MP, et al. Declining estrogen receptor-
beta expression defines malignant progression of human breast neoplasia.
Am J Surg Pathol 2003;27:1502-12.
11. Fuqua SA, Schiff R, Parra I, et al. Estrogen receptor beta protein in
human breast cancer: correlation with clinical tumour parameters. Cancer
Res 2003;63:2343-39.
12. Nakopoulou L, Lazaris AC, Panayotopoulou, et al. The favourable
prognostic value of oestrogen receptor beta immunohistochemical expression
in breast cancer. J Clin Path 2004;57:523-28.
Intracavitatory metastases may either be left-sided, as documented
in a recent case report1, or right-sided, as documented in two previous
case reports2,3, both cases in the latter two reports2,3
characterised by symptomatic right-sided cardiac failure attributable, in
the second of the two cases to the fact that tumour cells originating from
the right intracavitatory...
Intracavitatory metastases may either be left-sided, as documented
in a recent case report1, or right-sided, as documented in two previous
case reports2,3, both cases in the latter two reports2,3
characterised by symptomatic right-sided cardiac failure attributable, in
the second of the two cases to the fact that tumour cells originating from
the right intracavitatory secondary deposit had been seeded into the
pulmonary circulation3(fig. 4), mimicking pulmonary thromboembolism. The tumour itself was composed of papillary glandular epithelium with vesicular nuclei charcterised by moderate mitotic activity.
What also distinguished the intracavitatory deposit in the latter case was
that no primary tumour could be identified, even after an extensive post-
mortem examination. This was contrary to the expectation that cardiac
metastases are typically associated with an identifiable primary tumour,
as was the case in 56 out of 57 patients with cardiac metastases
documented in one necropsy study4. Arguably, as well, the seeding of
tumour deposits from the right intracavitatory tumour deposit to the
pulmonary circulation was an example of what might be better termed
"tertiary" dissemination, given the fact that it originated from an
identifiable secondary deposit, via a haematogenous route unique to the
site of that secondary deposit, rather than being an example of secondary
dissemination from an unknown primary. This implies that, in that
particular instance, the heart itself was the sole site of secondary
dissemination from the unknown primary. For the heart to be the "only
target of metastases" is distintly unusual, having been documentd in only
10 out of 662 cases in one series, all ten of those cases having an
identifiable primary site of origin of the cardiac metastases5.
Oscar M Jolobe
References
(1) Gupta K., Joshi K., Aggarwal AN., Vaiphei K
Asymptomatic polypoidal intracavitatory cardiac metastases from pulmonary
adenocarcinoma
Journal of Clinical Pathology 2008:61:142
(2) Hull HK., Usmani O
Intracavity right ventricular metastasis
Lancet 2006:367:424
(3) Jolobe OMP
Cor pulmonale: variation on a theme
Postgraduate Medical Journal 2001:77:675-77: correction of erratum in
Postgraduated Medical Journal 2002:78:62
(4) Metastatic and invasive tumours involving the heart in a geriatric
population: a necropsy study
Virchows Archiv A Pathological Anatomy and Pathology 1991:419:183-9
(5) Bussani R., De-Giorgio F., Abbate A., Ailvestri F
Cardiac metastases
Journal of Clinical Pathology 2007:60:27-34
The TMPRSS2-ERG has been described in several prostate cancer patients' cohorts. The article by Ashish et al. describes the frequency of this fusion in another patient cohort. It further demonstrates that the frequency of TMPRSS2-ERG is increased in moderate to poorly differentiated tumors. We would like to congratulate the authors on their interesting study and advocate that more work still has to be carrie...
The TMPRSS2-ERG has been described in several prostate cancer patients' cohorts. The article by Ashish et al. describes the frequency of this fusion in another patient cohort. It further demonstrates that the frequency of TMPRSS2-ERG is increased in moderate to poorly differentiated tumors. We would like to congratulate the authors on their interesting study and advocate that more work still has to be carried out to investigate and characterize the true frequency and association of TMPRSS2-ERG gene fusion in prostate cancer. Earlier reports have generated conflicting results about the association of the TMPRSS2-ERG with Gleason score. It has been demonstrated earlier that the rate of fusion positive tumours is actually lower in the poorly differentiated tumours.1 This latest finding was confirmed by our own study (data not published). These results should be further confirmed in larger and multiple cohorts as we investigate the TMPRSS2-ERG gene fusion as a biomarker of aggressive prostate cancer.
References: 1. Tu et al Modern Pathology (2007) 20, 921-928
We thank the reader for the careful and critical evaluation of our publication “Value of multicolor Fluorescence in situ Hybridization (UroVysionTM) in the differential diagnosis of flat urothelial lesions” published by Stephan Schwarz, Michael Rechenmacher, Tomas Filbeck, Ruth Knuechel, Hagen Blaszyk, Arndt Hartmann and Gero Brockhoff. The reader realized some inconsistency in the Material and Methods section of our paper r...
Dear Editor
In the section Methods the authors described Immunohistochemistry of HER2. The described protocol is an inconsistent mixture of a manual and automated immunostaining procedure and it is very unlikely that it was actually applied.
In a second sentence the authors stated that “a manual avidin-biotin peroxidase complex procedure was used in the immunohistochemical analysis according to the ma...
Dear Editor
We read with interest the article by K. Swe Swe and coauthors (1), which enriches our knowledge about non-typhoidal salmonella meningitis. From our own experience, we know that there are unexpected difficulties in addressing some aspects of this rare disease, which may result in inaccuracies. The authors stated that 10 out of total 17 cases of this rare infection have been reported in adults lacking po...
Dear Editor
I fully endorse the recommendations of Reddy and co-workers concerning management of potential Brucella isolates and those staff potentially exposed 1. The authors highlight that clinical information may not always suggest potential brucellosis, especially if time has elapsed since exposure, thus suspicion may not be raised. The authors then proceed to describe four blood culture isolates obtained from patien...
Dear Editor.
I was interested to read the article by Zheng and colleagues in the July 2007 edition of the Journal of Clinical Pathology 1, wherein the authors describe detection of Jamestown Canyon virus in human tissue samples. I write to urge caution as I fear that a simple unfortunate error has been made.
Jamestown Canyon virus is a bunyavirus belonging to the ‘California serogroup’, an enveloped, sing...
Dear Editor,
In the context of clinically suspected non-thyroidal illness(NTI) the advice to retest patients with raised levels of thyroid stimulating hormone(TSH)(1) may extend even to those in whom TSH levels are in the range 20-32.4 mIU/L(2). In one study, over a period averaging 88 days(Standard Error ie SE=34), seven such subjects, with mean baseline TSH of 32.4 mIU/L(SE=3.6), experienced a spontaneous fall in...
Letter to the Editor - Sputum sampling, storage and recovery: accuracy and sensitivity for Mycobacterium tuberculosis
Dear Editor,
The recent article by Pye et al. discusses the recovery of bacteria from sputum specimen samples stored at different temperatures (1). This article highlights sample handling, storage and transport, from the field to the clinical laboratory. This may be important in the fiel...
Dear Editor
We read with interest the paper by Borgquist et al (2008), published recently in Journal of Clinical Pathology1. In their article the authors aimed to investigate the impact of ERbeta expression on breast cancer outcome using a cohort of 512 tumours represented in tissue microarray (TMA). Since the discovery of ERbeta over a decade ago, this has been the goal of many research groups. However pr...
Dear Editor
Intracavitatory metastases may either be left-sided, as documented in a recent case report1, or right-sided, as documented in two previous case reports2,3, both cases in the latter two reports2,3 characterised by symptomatic right-sided cardiac failure attributable, in the second of the two cases to the fact that tumour cells originating from the right intracavitatory...
Dear Editor
The TMPRSS2-ERG has been described in several prostate cancer patients' cohorts. The article by Ashish et al. describes the frequency of this fusion in another patient cohort. It further demonstrates that the frequency of TMPRSS2-ERG is increased in moderate to poorly differentiated tumors. We would like to congratulate the authors on their interesting study and advocate that more work still has to be carrie...
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