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Pathology > Biomarkers > Flashcards

Biomarkers Flashcards

1
Q

Carcinoma general biomarkers

A

Broad spectrum cytokeratin (CK)
AE1/AE3 (broad)
MNF116
Cam 5.2 (LMWCK only)

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2
Q

Lymphoma general biomarkers

A

CD45

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3
Q

B-Cell lymphoma general biomarkers

A

CD19
CD20
CD79a
PAX5

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4
Q

T-cell Lymphoma general biomarkers

A

CD2
CD3
CD43

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5
Q

Melanoma general biomarkers

A

SOX-10
Melan-A
S-100
HMB-45

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6
Q

Sarcoma general biomarkers

A

CD34
MDM2

Really depends on the specific sarcoma

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7
Q

Mesothelioma general biomarkers

A

Calretinin
WT1
CK5/6
D2-40

Usually CK7+/CK20- like lung adenocarcinoma

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8
Q

Neuroendocrine general biomarkers

A

Chromogranin
Synaptophysin
CD56
INSM1 - newer marker, potentially to most sensitive/specific of all these markers

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9
Q

Germ cell tumour general biomarkers

A

SALL4 (pan germ cell marker)
OCT4 (very sensitive and specific for seminoma and embryonal carcinoma)

SF1 is very sensitive and specific for sex cord stromal tumours.

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10
Q

Adrenocortical tumour

A

SF1

Inhibin
Synaptophysin
Melanoma A
Typically negative on AE1/AE3 and other broad spectrum CK tests

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11
Q

CK7+/CK20+ differentials

A

Urothelial
Peridiaphragmatic Gastrointestinal (gastric, pancreatic, biliary ie cholangiocarcinoma)

Note:gastric is almost equally distributed between all CK20/7 profiles

Others: mucinous ovary, mucinous lung

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12
Q

CK7+/CK20- differentials

A

Above diaphragm:
Lung (adeno, small cell)
Breast
Salivary glands
Thyroid

Female GYN: Ovary (serous), uterus

Others: mesothelioma, renal (papillary), gastric/pancreatic/gallbladder (more often also CK20+)

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13
Q

CK7-/CK20+ differentials

A

Colorectal
Merkel cell

Others: gastric (more often also CK7+)

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14
Q

CK7-/CK20-

A

Simple visceral epithelium
Prostate
Liver (hepatocellular)
Kidney (renal clear cell)
Neuroendocrine cells

Others: adrenocortical, lung small cell, germ cell non-seminomatous, gastric

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15
Q

What type of epithelial tissue is generally associated with CK7

A

Glandular epithelium.
But also squamous epithelium of H+N, cervix

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16
Q

What type of epithelial tissue is generally associated with CK20

A

Epithelium of lower GI ready, umbrella cells of urothelium, Merkel cells

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17
Q

Are cytoplasmic/membranous or nuclear transcription factors more specific in undifferentiated adenocarcinomas?

A

Nuclear transcription factors.
-Protein correlates of genetic events

Cytoplasmic/membranous marker expression usually not additive to nuclear marker expression

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18
Q

What adenocarcinoma nuclear markers are commonly associated with
-breast
-lung
-gastrointestinal
-renal
-prostate
-thyroid

A

Breast: GATA3
Lung: TTF1, Napsin A
Thyroid: TTF1, PAX8
Gastrointestinal: CDX2, SATB2
Renal: PAX8
Prostate: NKX3-1, ERG

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19
Q

What cancers are positive for TTF1? What rates of positivity

A

Lung adenocarcinoma (70-100%)
Thyroid (80-100%)
Lung squamous (<10%)
Biliary (5-25%)
Ovarian (5-30%)
Endometrial (5-20%)
Breast, pancreatic, colorectal (<5%)

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20
Q

What cancers are positive for GATA3? What rates of positivity?

A

Breast (92-100%)
Urothelial (80-90%)
Skin squamous (80%)
Lung (5-10%)
Mesothelioma (25-60%)

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21
Q

What cancers are positive for CDX2

A

Colorectal (>90%) (CK7-/CK20+)
Oesophogogastric/pancreatobiliary (40-60%) (CK7+ CK20+/-)

Mucinous ovarian (40-60%)
Mucinous lung (70-80%)

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22
Q

What two markers are used to distinguish lung adenocarcinoma from SqCC. What is the nomenclature if both are negative or both positive?

A

TTF1 - adenocarcinoma
P40 - SqCC

TTF1-/p40- non small cell carcinoma NOS
TTF1+/p40+ non small cell carcinoma with adenocarcinoma and squamous differentiation

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23
Q

What markers are used first line to distinguish lung adenocarcinoma from mesothelioma (2 from each)

A

Adenocarcinoma: TTF-1, Claudin-4, napsin A
Mesothelioma: Calretinin, WT-1, CK5/6, D2-40

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24
Q

What are the TCGA molecular subtypes of breast cancer

A

Luminal A: ER strong positive, HER2 neg, Ki-67 low. good prognosis
Luminal B: ER weak positive, HER2 +/-, Ki-67 higher. Intermediate prognosis
HER2: ER/PR +/-, HER2 positive. Poor prognosis
Basal: triple negative. Poor prognosis

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25
Q

What is the Allred score

A

oestrogen/progesterone receptor score. Scores percentage positive and intensity of positivity

26
Q

What is the process for testing of HER2 status

A

IHC first. Score 0-3
Score 0-1: negative
2: equivocal, requires FISH (or D-ISH)
3: positive, does not require FISH confirmation

27
Q

What are the four proteins tested for with IHC to check for MMR deficiency in colorectal cancer

A

MLH1, MSH2, MSH6, PMS2

28
Q

What malignancies are associated with BRAF600E mutation

A

Melanoma
Colorectal carcinoma
Papillary thyroid carcinoma
NSCLC
Hairy cell leukaemia
Langerhans cell histiocytosis

29
Q

What are the 4 key prognostic and predictive bio markers in endometrial carcinoma

A

POLE mutation (molecular testing): excellent prognosis
MSI-H mutation (MSI) (IHC or molecular): intermediate prognosis
TP53 mutation (IHC or molecular): poor prognosis
No specific molecular profile (NSMP): intermediate prognosis

30
Q

What is MSI and how does it relate to dMMR?

A

Microsatellite instability is a genetic result of deficient mismatch repair. Tandem repeats of nucleotides throughout the genome become variable in length as opposed to being very constant where mismatch repair is normal.

Ie, dMMR can be tested by:
-IHC testing for abnormal levels of key mmr proteins
-molecular testing to detect downstream MSI

31
Q

What is Lynch syndrome

A

Also known as hereditary non polyposis colon cancer (HNPCC)
Inherited deficiency in one of the MMR proteins. Most commonly MSH2 and MLH1

32
Q

What is the most common mechanism of sporadic dMMR

A

Epigenetic silencing of MLH1 (MLH1 promoter methylation)
Ie, not mutation of the gene

33
Q

What are the four molecular subtypes of gastric adenocarcinoma?

A

CIN: chromosome instability (assossiated with H pylori): most common. Intermediate prognosis. Frequent TP53 mutations

Micro satellite instability (MSI): intermediate prognosis

EBV virus associated: intermediate to excellent prognosis. Often have PD-L1 over expression

GS: genetically stable. Poor prognosis. Predominantly signet ring morphology, CDH1 mutation (e cadherin)

34
Q

What are the key mutations/ abnormalities in melanoma affecting targeted therapy options?

A

PD-L1 (pembro)
BRAF (Vemurafenib)
NRAS (resistance to vemurafenib, ?MEK inhibitors)
KIT mutation (Imatinib)

35
Q

What IHC tests can be used to distinguish site of origin for WELL DIFFERENTIATED neuroendocrine tumours?

A

TTF1+: lung
CDX2+: midgut/small bowel
PR/pPAX8+/SATB2-: pancreas
SATB2+/TTF-: rectum or appendix
IL1: pancreas or rectum

36
Q

Define diagnostic biomarker

A

A marker used to help diagnose a cancer including subtyping

37
Q

Define prognostic factor

A

A factor which forecasts how aggressive a cancer is. Ie determines the patients ability to fare in the absence of treatment

38
Q

Define predictive factor

A

A factor which predicts how well a cancer will respond to a certain treatment

39
Q

What is IHC and how does it work

A

Immunohistochemistry. Uses immune markers to detect protein surrogates for gene mutations. (1 protein surrogate per gene)

40
Q

What is FISH and how does it work

A

Fluorescent in situation hybridisation. Fluorescent markers attach directly to abnormal gene. There are methods other than fluorescence

41
Q

What is PCR, how does it work

A

Polymerase chain reaction. Can be used to detect multiple mutated genes in one test. (1-3)

42
Q

What is NGS and how does it work?

A

Next generation sequencing. Massive parallel sequencing that tests for many mutation in one panel

43
Q

What are some markers of smooth muscle

A

Desmin
Smooth muscle actin
Muscle specific actin

44
Q

What are AE1/AE3 and Cam 5.2 testing

A

Both are antibody cocktails that broadly test for CK positivity, aiming to check if a poorly differentiated malignancy is a carcinoma.

45
Q

What is the best bio marker to distinguish lung adenocarcinoma from mesothelioma

A

Claudin 4 (negative in mesothelioma.)

46
Q

What are the most useful IHC tests for prostate cancer

A

PSA (cytoplasmic): high sensitivity and specificity
NKX3.1 (nuclear)

47
Q

What IHC tests can be used to attempt to distinguish colorectal from bladder adenocarcinoma

A

B-catenin: nuclear in colorectal, cytoplasmic (normal) in bladder
CDX2, SATB2: positive colorectal. Variable bladder
CK20: positive colorectal, variable bladder.

Ie b-catenin is most useful.

48
Q

What is the usual CK7/CK20 profile of urothelial carcinoma

A

Both positive

49
Q

What IHC profiles can be used to distinguish the different forms of thyroid cancer

A

TTF1: follicular/papillary/medullary
Thyroglobulin: follicular/papillary
PAX8: follicular/papillary, others variable
AE1/AE3 or Cam5.2: all generally positive
PTH/GATA3: parathyroid
Neuroendocrine markers: medullary, parathyroid

50
Q

What is the typical immune profile of pancreatic adenocarcinoma

A

CK7/CK20+
CA19-9+
CEA+
Loss of expression of SMAD4

51
Q

What is the typical IHC profile of small cell lung carcinoma. How does this compare to carcinoid tumours

A

TTF1 positive
Synaptophysin, chromogranin, ISNM1, CD56 frequently only weak focal positivity
Ki67 very high %

Carcinoid have strongly positive neuroendocrine markers, very low Ki67 and TTF1 can be positive or negative

52
Q

What should be tested to attempt to differentiate mesothelioma from reactive mesothelial proliferation

A

BAP1 IHC: loss of expression consistent with mesothelioma
p16/CDKN2A/9p21 FISH: loss of 9p21 locus consistent with mesothelioma.

Note that this testing is 100% sensitive, but does not rule out mesothelioma if both are retained

53
Q

What cancers are positive for PAX8

A

Thymoma/thymic carcinoma
Renal
Thyroid
Mullerian (endometrial, endocervical, ovarian)

54
Q

What will happen to B-catenin staining when there is loss of e-cadherin

A

Membrane staining will be lost (as it is not being held at the cell membrane by e cadherin

55
Q

What are potential patterns of abnormal p53 IHC staining

A

Over expression (due to defective p53 being over expressed as negative feedback doesn’t happen)
Negative (mutation decreases p53 production)
Normal expression (no abnormality, so there will be some staining of normal p53)

56
Q

Inva

A
57
Q

What is the main relevance of vimentin

A

Classical thought to distinguish sarcoma from carcinoma, but now recognised that is is positive in many carcinomas, so it is no longer used routinely.

Main use is to check if tumour is viable for immune staining when everything else is coming up negative

58
Q

What is the specificity of CEA IHC

A

Not very specific except:

HCC: canalicular staining with pCEA.

59
Q

Are Neuroendocrine tumours CK positive, and what is the usual pattern

A

Positive: Epithelial origin NETs. Eg, carcinoids, small cell lung ca, Merkel. staining very variable, can be difficult to see due to scanty cytoplasm of small cell carcinomas. Dot-like pattern cytoplasm staining, likely due to clumping of CKs.

Negative: pheo, paraganglioma, neuroblastoma

60
Q

What staining pattern indicates p16 IHC positivity

A

Must be block-like strong nuclear and cytoplasmic staining.
Patchy or weak staining is negative

61
Q

What IHC markers are associated with endothelial/vascular origin tumours

A

ERG
CD34
CD31

62
Q

What are tumours common,y associated with c-kit mutation

A

GIST
Seminoma
Melanoma (mucosal)
Thymic carcinoma
Some salivary neoplasms

Pathology (16 decks)

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