Pathcare May-Aug.pdf

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May-Aug 2011

Vol. 2

Molecular Testing in Solid Tumours

Laboratory Diagnosis of Malaria

Purpose,Values and Aspirations

Lab Diagnosis of Brucellosis

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East AfricanPathology Forum


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East African

Dr Jane Mwangi Dr Kiran Radia

[email protected]

[email protected]

[email protected]

www.pathcarekenya.com

Assistant Editor

Benjamin Matheka

Operations Manager

Madhu Aggarwal

Technical Manager

Paul Okwach

Financial Controller

Charity Njuguna

Marketing Manager

Benjamin Matheka

C.E.O/Chief Pathologist

Dr Kishor MandaliyaCoast Pathologist

Purpose, Va lues and Aspi ra tions Molecular Tes ting in Solid Tumours

Laboratory Diagnosis of Malaria Laboratory Diagnosis of Brucellosis

From the Editor

Laboratory tests have become increasingly sophis-ticated in recent years and this has increased the

importance of the laboratory in assisting cliniciansin diagnosis and management of patients.

Molecular pathology is rapidly developing and anever-changing science. In this issue we have an

article on molecular testing in solid tumours.Wetrust that you will find the information useful and

that it will assist you in the understanding of the

most modern techniques Pathcare has.

Malaria continues to be a serious public healthproblem and our haematopathologist contributes a

review on the laboratory diagnosis of malaria.

The number of tests utilizing PCR-technology isgrowing at a spectacular rate.

Brucellosis has for many years been a difficultdisease to diagnose, confirm cure and predictrelapses and has now also succumbed to the PCR

wave. In this Forum we compare the use of conven-tional culture and serology for the diagnosis ofbrucellosis with the much more accurate and

reproducible PCR-test.

On the facing page you can read a statement about

Pathcares Purpose, Values and Aspirations.This demonstrates the philosophy that underpins

what we represent.

E-mail

East African

laboratory tests in all the clinical settings viz. acute brucellosis, chronic

infections, focal infections, follow-up of treatment and prediction of

relapses.

Blood culture: These tests take up to 7 days to produce a result, have a

sensitivity of 74% in the acute phase but the sensitivity is significantly

reducedin thefocaland chronicformsof thedisease.

Serology tests have a poor sensitivity during the early stages of the

disease due to low levels of antibodies. Serological methods lack

specificity and titres often remain elevated for protracted periods after

therapy even in cases of complete recovery. Less than 25% of patients

show a significant rise in antibody titre during relapses. Serology has

serious limitations, especially in chronic, relapsing and focal forms of

disease.

Laboratorytests

Serology

Culture of the organism poses a high risk of contagion to the

laboratory staffandthereforeisnot performedatour laboratory.

Ifbuffycoat samplesare used,PCRtests have

been shown to have a 100% sensitivity and a

100% specificity in acute, chronic, relapsing

and focal forms of disease. PCR tests can

predict therapeutic failure and relapses with

almost 100%accuracy.

PCRtestingcanalsobedoneafter6 weeksof

effective treatment to ensure eradication of

brucella and thereby prevent the high rate of

recurrence.

Polymerasechain reaction(PCR)

It is t he re fore t he opinion of t his

laboratory that PCR tests should replace

t he c urrent serology t ests for t he

diagnosisof brucellosis.

Pathcare Kenya Limited staff attending to members of the public at the Westgate Shopping

Mall where they offered free testing for blood glucose and bl ood groupPathcare staff speaking to a client on the services we offer after undertaking

a free blood glucose and blood group test at the Westgate Shopping Mall

112

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the laboratory diagnosis of brucellosis

East African

Brucellosis is an occupational hazard among farmers, herders,

veterenariansand abattoir workers.

After entering the body, the bacteria spread via the bloodstream to

the liver, spleen, lymphnodes and bonemarrowwhere theymultiply

in macrophages, which undergo generalised hyperplasia. This may

lead to lymphadenopathy and hepatosplenomegaly (

and , thedevelopmento f noncaseat inggranu lomas in the

liver, spleen, lymph nodes and bone marrow or

suppur at ive li ve r abs cesse s .

The clinical symptoms of brucellosis are non-specific and several

otherfebrilediseasesmaybe mimicked.Featuresofacutediseaseare

variedand onset may be insidious. Acuteinfection canbe followedby

chronic infection, relapses (undulating fever) or focal forms of

infection. Features of chronic disease arevagueand maypersist or

recurforyears.

Therelapserateafterappropriateantibiotictherapycanbe ashigh as

30%. I t i s therefore impor tant to evaluate the per formance of

B. melitensis

B. abortus)

(B. abortus)

(B. suis)

Clinicalbackground

Brucellosis is a febrile bacterial disease acquired from

domestic animals and encountered worldwide.FourBrucella species, each with its own animal reservoir, cancause human disease i.e. B. abortus (cattle), B. suis(swine), B.melitensis (sheep and goats) and B. canis(dogs). Of the four, B. melitensis is the commonest causeof symptomatic disease in humans.

Humans are infected with the bacteria through:

Contact with infected blood or tissue;

Ingestion of contaminated meat or milk;

Inhalation of contaminated aerosols.

Written & Compiled byDr Pierr Schoeman

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Gametocyte of P. falciparumin blood film

Rapid diagnostic testP. falciparum in thinblood film

9

East AfricanEast African

Fluorescence basedmicroscopytests:Acridine orange, a fluorescent dye, has affinity for nucleic acids. Thequantitativebuffycoatmethod(QBC)uses acridineorangeand a concentrationtechnique to enhance detection of the malaria parasite. An acridine orangecoated capillary filled with 50-100 l blood is centrifuged and the buffy layer isexamined under a fluorescent light microscope for the presence of red cellscontainingparasites.The sensitivityofthe QBCmethodhas beenreportedto bebetween55% togreaterthan90% (2).

NewtestsReal time PCR has recently beenadapted to detect all four humanm a l a ri a p a r as i t e s w i t h 1 0 0 %sensitivity and specificity and allowquantification (5). The real time PCRassay offers a practical and clinicallyacceptable alternative for rapid andaccurate diagnosis of malariainfestations in patients presenting

with symptoms of this disease andshould in future, when suitablecommercial kits are available, bei n c o rp o r at e d i n t o d i a g no s t i ca l go r it h ms a s a n a d ju n ct t omicroscopicand immunologicaltests.

Ina diseaselike malariawheremisdiagnosisresultsin significantmorbidityandmortality and taking into account the limitations of the diagnostic tests, thefollowingissuggestedasa decisionchartfortreatment:

SUSPECTED CLINICAL CASES

Treatmentprotocol

Treatmentprotocol

Severe malaria Treatment

protocolUncomplicated

malariaTreat whileexcluding

other disease

P. falcipar um Non-

falciparumHigh suspicion

of malaria

Look for otherdisease Review

and repeatsmears Refer

Microscopy / RDT

Positive Negative

References:

1. MalariaWorkingPartyofthe GeneralHaematologyTaskForceof theBritishCommittee for Standards in Haematology.Thelaboratorydiagnosisof malaria.ClinLabHaem1997(19) 165-170.

2. Hnscheid,T.Diagnosisofmalaria:areviewofalternativestoconventionalmicroscopy. ClinLabHaem1999 (21)235-245.

3. http://www.wpro.who.int/sites/rdt/documents/TheUseof MalariaRapidDiagnosticTests.

4. http://www.wpro.who.int/sites/rdt/documents/Malaria Diagnosis:Newperspectives:WHO2000.

5. PerandinF.et al.Developmentof real-timePCRassayfordetectionof

forroutineclinicaldiagnosis.JClinMicrobiol2004(42)1214-1219.

6. http://rbm.who.int/wmr2005.WordMalariareport2005.Preparedby: RollBackMalaria.

WorldHealth Organization.UNICEF.

Plasmodium

falciparum,Plasmodium vivax,and

Plasmodiumovale

In the past 2 decades the analysis of protein expression by

immunohistochemical staining has become an integral tool for assessment

of pathology specimens. More recently, molecular testing is being integrated

intoveryspecificareasindiagnosticpathology.

This overview will provide some examples of molecular tests in different

stagesof clinicalapplicabilityin afew differentorgansystems.

Colorectal adenocarcinomas arise through different genetic pathways and

should no longer be considered one disease. The majority (85%) of

colorectal cancers arise via the chromosomal instability pathway with

dysfunction of the APC/Beta-catenin/WNT signalling pathway. However15% to 20% of colorectal cancers arise via the microsatellite instability

pathway (MSI), owing to either a germline mutation (Lynch syndrome) or

epigeneticgene silencingsecondary tohypermethylation.

Four main proteins, MLH1, MSH2, MSH6 and PMS2 comprise the

mismatchrepair complex.

Carcinomas arising via the MSI pathway have characteristic pathologic

features. Antibodies to the above proteins can be used to screen for

Microsatelliteunstabletumours(MSI-H)(Seefigure1).

MolecularPathology ofColorectal Adenocarcinoma:

Molecular testing in anatomic pathology will almost certainly become

critical for providing optimal patient care during the next 5 to 10years, asmore assays are developed that provide valuablediagnostic,prognostic and

therapeut ic informat ion for patient management.

Traditionally pathologists have relied on thehaematoxylin-e osin-stained

slide to make a diagnosis. Prognostic indicators were limited to those thatcould be seen at the light microscopic level and included such variables asthe surgical margin status, lymph node metastasis and perineural and

angiolymphatic invasion.

Characteristic intact nuclear staining with MLH1 in a patient with amicrosatellite stable cancer. This pattern of staining would be present for all

fourmismatchrepairproteinantibodies(MLH1,MSH2,MSH6,andPMS2).

Figure1:

15MSI-H

2HNPCC

methylation,

CIMP+

chromosomal

instability

85MSS/MSI-L

Suchscreeningmethodscanidentifypatientswho shouldhaveadditional

genetic testing and counselling. Molecular testing using a panel of

microsatellite markers can detect MSI-H tumours. Most MSI-H colorectal

cancersare sporadicandarisefromepigeneticgenesilencingof oneof the

mismatch repair protein genes, most commonly . A minority of

MSI-H colorectal cancers are inherited (hereditary non-polyposis

colorectal cancer) and arise from germline mutation of one of the

mismatch repair genes or .

A subset of colorectal carcinomas (25%) has widespread aberrations in

DNA methylation, including promoter silencing of genes that are

important to tumour biology. Referred to as the CpG island methylator

phenotype (CIMP) this includes most sporadic MSI-H cancers with

methylation silencing of . CIMP testing can be done to detect

abnormalDNAmethylation(SeeTable1).

Breakdownofthe molecularpathogenesisof colorectalcancers.

MLH1

MLH1,MSH2,MSH6 PMS2

MLH1

Table1

Written and Compiled by

DrLindaSteyn

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otiuqsomselehponAairalamfonoitubirtsiD kcihtnietisarapairalaMblood film

East African

8

East African

the laboratory diagnosisof malaria

Misdiagnosis of malaria results insignificant morbidity and mortality. Rapidand accurate detection, speciation andenumeration of malaria parasites has animportant role in addressing this and inpromoting rational use of increasingly

costly drugs. The tests that are availabletoday include microscopy (thick smear,thin smear, fluorescence microscopy),antigen detection and detection ofparasites with the polymerase chainreaction(PCR).

At PathCare we follow guidelines fordiagnosis of malaria as prepared by theMalaria Working Party of The GeneralHaematology Task Force of the BritishC o m m i tt e e f o r S t a n d a r d s i nHaematology. The recommendationsstate the following - both thick and thinblood films should be examined andmicroscopy may be supplemented by animmunological or fluorescence basedmethod(1).

Written & Compiled byDrIllseLouw

Interpretationof RDT's:

Thick film and thin films:The thick film is used for the detection of the parasites and the thin film is usedfor species identification. When a minimum of 200 oil immersion fields (x100objective)is viewed ona thickfilm,approximately0.50l ofblood isexamined.The detection limit of a thick film is 5-20 parasites per l. When 100 oilimmersion fields (x100 objective) of a thin blood film are viewed, 0.005 l ofblood is examined. The detection limit of a thin blood film is 50-200 parasitesperl(2).

RDTs generally achieve a sensitivity of >90% in the detection of atdensities above 100 parasites per l blood (4) and the specificity of RDT's isuniformly high (mostly >90%). Limitation of the tests include limited speciesidentification, false positive results which have been reported in patients withrheumatoid factor in kits testing for the HRP2 antigen (4), and HRP2 testsremaining positive for 7-14 days following chemotherapy in a proportion ofindividuals, even though these patients no longer have symptoms orparasitaemia(as assessedby bloodsmears),thus limitingthe useof theRDT'sinfollow-upof treatment(2).

Kits that incorporate testing for both the panmalaria aldolase and HRP2, to

detec t both and non- speci es , cannot di ffe rent ia tebetween and nor can they distinguish pure

infectionsfrommixedinfectionsthatinclude (4)

Immunologicaltests:Immunologicaltests formalariaarealso knownasrapid diagnostictests(RDTs).These tests are based on the detection of antigens derived from malariaparasites in lysed blood, using immunochromatographic methods. The three

hcir-eniditsiheradetcetedylnommoceratahtsnegitnaprotein 2 (HRP2), a panspecific malaria aldolase and parasitespecific lactatedehydrogenase. The RDT currentlyin use at Pathcare detects the HRP2 of

anda panspecificplasmodiumaldolase.

Plasmodium falciparum

P. falciparum

P. falcipa rum

P. fac ilpa rum falcipa rumP. vivax, P. ovale P. malariae,

murapiclaf.Pmurapiclaf.P

CONTROL LINE POSITIVE

HRP2 line only positive

infection orinfection plus

infection with non-falciparumspecies of such low levels thatthe aldolase antigen does nottest positive

P. falcip arum

P. falcip arum

HRP2 and aldolase linespositive

or mixedinfection withP. falciparu m

P. falciparum, vivax,ovale, malariae

Aldolase line only positive

infectionNon-falciparum

Recent studies have shown that status, EGFR amplification and

expression of were associated with outcome measures in

wild-type patients treated with a cetuximab-based regimen. Subsequentstudieswill berequiredtoconfirmtheclinicalutilityof thesemarkers.

Sequence electrophoretogram of the PCR product of exon 15

showing two overlapping peaks at position 1799, which is diagnostic of

aT Amutationatthisposition.

Approximately 5% to 10% of breast cancers are caused by mutations inhigh penetrance breast cancer susceptibility genes and include

and . These genes confer a high risk of breast and ovarian cancer.

Two genes associated with rare cancer syndromes, and also

conferaveryhighriskof breastcancer. associatedbreastcancers

havedistinctmorphology,beingmoreoftenmedullary-like,triplenegative

a nd sho wing a ba sa l p heno type. a nd c an cers a re a

heterogenous group without a specific phenotype. At present the role of

and in DNA repair is being exploited to develop novel

therapies (Poly-ADP ribose polymerase inhibitors). A number ofl ow to

dnaicol/senegtnartenepetaredom

have also been identified but their role and contribution in breast cancer

developmentisstillunderinvestigation.

BRAF

PTEN KRAS

BRAF

BRCA1

BRCA2

P 53 P TE N

BRCA1

BRCA2 BRCAX

BRCA1 BRCA2

9FGFR2, TNRC9, MAP3K LSP1

Figure2

MolecularPathology ofBreast Tumours

The clinical detectionof colorectalcarcinoma withdeficient mismatchrepair

functionis desirablefor3 reasons:

1. Identification of Lynch syndrome (HNPCC). Confirmation of the

germline mutation allows for the most accurate treatment and follow-up

recommendations for the patient and allows predictive testing to be

undertakenininterestedfamilymembers.

2. Microsatellite instability is also a predictor of chemosensitivity including

5-fluorouraciland irinotecan.

3. MSI-Hcarcinomaisassociatedwitha morefavourableprognosis.

Based on available evidence regarding risk and outcome, mismatch repair

gene mutation carriers should be offered colonoscopy every 1 to 2 years

beginningat20 to25 yearsofage.

Subtotal colectomy is generally favoured for patients with known HNPCC-

Lynch syndrome; however the potential benefit over colonoscopic

surveillancehasnotbeenstudied.

Approximately 20% of patients with colorectal cancer present withmetastatic disease and an additional 30% to 40% develop metastases

during the course of their disease. Adjuvant therapy is usually used in

patients with advanced stage disease. In particular epidermal growth factor

receptor (EGFR) inhibitor therapies have emerged as effective treatments in

a subset of patients with metastatic colorectal carcinoma. Mounting

evidence has shown that these therapies are ineffective in tumours with

mutations of codons 12 and 13 of exon 2 of the gene (see Figure 2 ).

Because of this compelling data the determination of mutation status

isrecommendedin allpatientswith metastaticcolorectalcarcinomawhoare

candidates for anti-EGFR therapy. However only half of these patients will

benefitfrom treatment,suggestingthe needto identifyadditionalbiomarkers

forcetuximab-based treatmentefficacy.

KRASMutationtestinginColorectalCancer

KRAS

KRAS

FromHistopathology 50:113-130,2007

CIMP, CpG methylator phenotype; MSI-H, high frequency microsatellite instability; MSI-L low frequency microsatellite instability; MSS microsatellite

stable

Recently, a molecular-pathologic classification of colorectal carcinoma has been proposed that is based on the presence or absence of aneuploidy and the

statusofmismatchrepairandmethylationpathways.(SeeTable2)

MolecularPathologic Classificationof ColorectalCancer

Table2

1

2

3

4

5

CIMP

high

CIMP

high

CIMP

low

CIMP

negative

CIMP

negative

Partial

Methylation

Microsatellite

MSI-H

MSS/MSI-L

MSS/MSI-L

MSS

MSI-H

Chromosomal

Status

Stable

diploid

Stable

diploid

Stable

diploid

Unstable

diploid

Unstable

diploid

Precursor

Adenoma

Adenoma

Proportion

12%

8%

20%

57%

3%

5

At the end of 2 004 3 .2 billion peoplelived in areas at risk of malaria t r a ns m i s s i o n . An estimated 350-500million clinical malaria episodes occurannually, most caused by P.falciparumand P. vivax. Falciparum malariacauses more than 1million deaths eachyear.About 60% of the malaria casesworldwide , about 75% of globalfalciparum malaria cases and 80% ofmalaria deaths occur in Africa south ofthe Sahara (6).


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East African East African

utilizes expression array analysis of 70 genes to identify patients with

good and poor prognostic signatures. A further assay, PAM50 Assay

basedonintrinsicsubtypeswillalsobe availablesoon.

In brain tumours loss of 1p (short arm of chromosome 1) and 19q (long

arm of chromosome 19) is associated with oligodendroglioma

differentiation, being found in up to 80% of cases (See figure 4). This

mutational profile has also been shown to correlate with responses tochemotherapy. Anaplastic oligodendrogliomas with combined allelic

losses on 1p and 19q are typically sensitive to PCV chemotherapy.

Longer survivals have also been reported in patients with 1p and 19q

loss.

(A) This anaplastic oligodendroglioma, grade III, is more crowded with

more pleomorphic nuclei than the grade II oligodendrogliomas. Despite

their pleomorphism, nuclei tend to be round. Mitotic figures are

numerous.(H&E.)

(B)Crowdedhyperchromaticnucleido notoverexpressp53.

(C) Diffuse margin of this anaplastic oligodendroglioma in gliotic brain

highlightsGFAP-negative branchingmicrovascular proliferations.

(D) One of the deletions often found in oligodendrogliomas is on the short

armofchromosome1 (1p).

In this fluorescent in situ hybridization (FISH) preparation, the test probe

for1p32is redand thereferenceprobe for1q42isgreen.Each nucleusis

counterstained blue. The single red dot in each of the three whole nuclei

demonstrates a deletion on 1p. The reference probe shows two green

dots, reflecting a pair of chromosomes giving this signal, as expected in

these diploid interphase nuclei. FISH preparation was contributed by Dr.

Arie Perry, Division of Neuropathology, Department of Pathology,

WashingtonUniversity Schoolof Medicine,

St.Louis,Mo.

From McKeever PE. New methods of brain tumour analysis. In: Mena H,

SandbergG, eds.Dr.KennethM.EarleMemorialNeuropathologyReview.

Washington,DC: ArmedForces Institute ofPathology,2004.

Oligodendrogliomaand lossof1p and19q

Figure4

A

B

A

C

B

D

One of the most common applications of molecular pathology in solid

tumours is to test for amplification of gene (See Figure 3).

positive breast cancer is significantly correlated with several unfavourable

pathologic tumour characteristics. Herceptin was developed as a biologic

targetedtherapeuticagainstthe receptor.

-positivebreast cancer.

A: immunostain demonstrates intense membrane staining of alltum ou r c ells in a c hicken-wir e p attern in dic atin g p ro tein

overexpression(3+).

B: FISH assay using a dual probe system. Red signals denote gene

copiesand greensignalsdenotecopiesof chromosome17. Theaverageratio

of red to green signals per nucleus is >2.2; therefore, this tumour shows

gene amplification.

Two molecular tests are available that may aid in assessment of prognosis

andthe prediction ofresponsetovarioustherapeuticmodalitiesin individual

patients. Oncotype DX (Genomic Health Inc.) is based on the analysis of

expression of 21 genes and provides a recurrence score that correlates with

outcome.Mammaprint(Agendia)isa molecularprognostictestthat

HER2 HER2

HER2

HER2

HER2

HER2

HER2

HER2

Figure3

Conclusion:

Summaryof someofthecommonlyusedmoleculartestsin SolidTumours:

The aboveoutlines afew examplesof howmolecular pathologyis incorporatedand usedin clinicaland pathologypractice.

In the near feature, classification and diagnosis of most tumours through morphologic analysis will be supplemented by molecular information correlating to

prognosisand targetedtherapy.

References:

1. BelezziAM,FrankelWL.Colorectalcancerdueto deficiencyinDNAmismatchrepairfunction.Areview.Adv.AnatPath.2009;16(6):405-417.

2. ColemanWB,TsongalisGJ.MolecularPathology.Themolecularbasisofhumandisease.

3. DabbsDJ.DiagnosticImmunohistochemistry.TheranosticandGenomicapplications.

4. Hunt,Jennifer.Moleculartestingin solidtumours.AnOverview.ArchPatholLabMed.2008;132:164-167

5. Hunt,Jennifer.Moleculartestingin anatomicpathologypractice.Areviewofbasicprinciples.ArchPatholLabMed.2007;132:248-260.

6. OdzeRD,GoldblumJR.SurgicalPathologyofthe GItract,Liver,BiliarytractandPancreas

7. PlesecTP,HuntJL. MutationTestinginColorectalCancer.AdvAnatPathol.2009;16(5):196-203.

8. PuigPet al.Analysisof PTEN,BRAGandEFGRstatusindeterminingbenefitfromcetuximabtherapyinwild-typeKRASmetastaticcoloncancer.J

ClinOncol.20091-8.

9. TanasMR,GoldblumJR.Fluorescence in-situHybridizationintheDiagnosisofSofttissueNeoplasms:Areview.Adv.AnatPath.2009;

16(6):383-391.

10. TubbsRR,StolerMH.Celland TissueBasedMolecularPathology.OdzeRD, GoldblumJR.SurgicalPathologyof theGItract,Liver,Biliarytractand

Pancreas

KRAS

Mo le cu lar H ae mat opa th ol og y M ol ecu la r Pa th ol og y of S of t Ti ss ue Tu mo ur s

Molecular diagnostic techniques have become an important part of

modern haematopathology as several entities in haematopoietic and

lymphoid neoplasms are defined by their underlying molecular

abnormalities. Molecular pathology is used for diagnosis (neoplastic vs.

reactive), classification, prognosis and monitoring (response and early

recurrence). In routine practice most B-cell lymphoproliferative disorders

are diagnosed on the basis of morphologic and immunophenotypic

findings without need for molecular analysis. However moleculartechniques can be of clinical utility in several settings. Clonality studies

may be helpful in some cases. Several characteristic balanced

translocations are associated with distinct B-cell lymphoproliferative

disorders. Molecular studies to detect these translocations can therefore

be valuable in cases in which the morphologic and phenotypic findings

are not clearly diagnostic. Diagnosis of T-cell lymphoproliferative

disorders can be aided by T-cell receptor rearrangement and several

recurrentcytogeneticabnormalitieshave beendescribedin specifictypes

of T-cell lymphoproliferative disorders that may offer additional

assistanceindiagnosisorassessmentof prognosis.

More than any subset of solid tumours, the diagnosis of soft tissue neoplasms

(mesenchymal proliferations that occur in the extra-skeletal tissues of the body)

has become heavily reliant on molecular analysis as an adjunct to light

microscopic and immunohistochemical evaluation. This is because of the

challenging nature of the discipline and the difficulty of sorting through

diagnostic entities with overlapping histological and immunohistochemical

features. In addition a number of difficult diagnostic entities have characteristic

molecular alterations. Soft tissue tumours can be classified broadly into thoseneoplasms with complex and nonspecific cytogenetic and molecular genetic

features and those harbouring relatively simple cytogenetic profiles with

consistent and recurrent genetic aberrations. The most common

morphological/immunohistochemical categories in which molecular testing is

useful includes high grade round cell sarcomas, nonmyogenic spindle cell

sarcomas, low grade myxoid neoplasms, adipocytic neoplasms and

melanocyticneoplasms.

ORGAN

COLORECTUM

COLORECTUM

BREAST

BREAST

BREAST

BREAST

BREAST

HAEMATOPATHOLOGY

HAEMATOPATHOLOGY

TEST

R

Prognosis

Diagnostic

Mammaprint

APPLICATION

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