Role of Pathology in Cancer Diagnosis

Question 1

What is pathology?

Answer 1

The study of cause and effects of disease and injury

Question 2

What is molecular pathology?

Answer 2

Studying the molecules in organs, tissues or fluids to understand the cause and effects of disease

Question 3

What percentage of NHS diagnoses depend on pathology?

Answer 3

70%

Question 4

What fields/services count as pathology?

Answer 4

Biochem, haem, microbiology, virology, histopathology, cytopathology

Question 5

What are some pathology techniques

Answer 5

pathomorphology, PCR, FISH, cytogenetic arrays, flow cytometry

Question 6

Pathology is most important for what aspects of the patient pathway?

Answer 6

Diagnosis and classification and stratification

Question 7

Histology was one of the first mechanisms for cancer diagnosis and prognosis. What did they tend to look for down the microscope?

Answer 7

Nuclear atypia, mitotic activity, cellular density, tissue architecture

Question 8

What are the 5 histological cancer types? And what cell type do they come from?
C
S
M
L
L

Answer 8

Carcinomas (epithelial)
Sarcoma (mesenchymal, connective tissue)
Myeloma (plasma cells)
Leukaemia (begin in bone marrow)
Lymphomas (lymphocytes)

Question 9

What do you need to do and know and ask to working in histology?

Answer 9

Know organ anatomy and cellular anatomy.
Receive a fresh specimen.
Find out as much case info as you can, including what the surgeon has done and what the clinician needs to know.

Question 10

What steps are required for a good surgical resection for diagnosis?

Answer 10

Resect close to the margins. Determine all the cancer cells to know if it’s spread outside the margins.
Remove as many lymph nodes as possible to know the level of spread then teh grade can be correctly diagnosed.

Question 11

What are prognostic factors in histology?

Answer 11

The margins, stage, grade, vascular invasion, lymphatics, cancer datasets, molecular markers, and evidence based practice…

Question 12

How do you go from cancer to results in histology?

Answer 12

Remove a sample, place it on a slide, it will adhere. Fix, dehydrate, clean, embed, cut, stain. Then cell morphology stain AND/OR do a specific protein stain.

Question 13

Immunohistochemistry is….

Answer 13

Binding antibodies to specific proteins in tissues to stain and see protein expression

Question 14

Why might you want to stain for C-kit using IHC?

Answer 14

Imatinib can block the receptor activity of C-Kit

Question 15

Name the cancer that each of these proteins are stained for in IHC.
ALK
PTEN
NCAM1
EGFR

Answer 15

ALK - Lung
PTEN - Brain
NCAM1 - CRC
EGFR - Stomach

Question 16

Multiple markers may have to be used in IHC. Especially for what type of cancers?

Answer 16

Haematological

Question 17

Molecular pathology looks at which molecules?

Answer 17

DNA, RNA, and proteins.

Question 18

What techniques does molecular pathology use?

Answer 18

Karyotyping, FISH, PCR, RT-PCR, Microarray, protein array, Serum biomarker analysis (ELISA)

Question 19

Karyotyping can tell you what?

Answer 19

The disease itself or the stage of the disease

Question 20

What is the general karyotypic progression of CRC?
Hyperproliferation
Early adenoma
Late adenoma
Full carcinoma
Metastasis

Answer 20

Start with loss of 5q / FAP leading to hyperproliferation.
Then DNA hypomethylation in early adenoma.
12p KRAS mutation leads to intermediate adenoma.
18q loss/DCC mutation leads to late adenoma
17p p52 loss leads to full carcinoma
Then other alterations leading to metastasis.

Question 21

What will FISH detect in CML?

Answer 21

BCR-ABL fusions between chr9 adn chr22

Question 22

What are the 3 types of PCR? (for the purpose of this question anyway)

Answer 22

Single-plex
Multiplex
RT-PCR

Question 23

Explain the use of each type of PCR:
Single-plex
Multiplex
RT-PCR

Answer 23

Single-plex - EGFR mutations in NSCLC
Multiplex - Panels like EGFR, ALK, ROS1, BRAF and KRAS in NSCLC
RT-PCR - Accurate quantification. Amplification of HER2 in 20% of breast cancers. Which can be concomitant with amp/del of topo II which may determine a response to chemotherapy

Question 24

Array technologies screen many targets to build a disease-specific profile of diagnosis, prognosis, progression, and helps with therapy too. There are many platforms for it. What platform is used in CLL patients and for what purpose?

Answer 24

ZAP-70 is used in leukaemic cells of CLL patients to identify the correct IgVH mutational subtype

Question 25

What is serum biomarker analysis?

Answer 25

Serum biomarkers are those proteins in the serum part of blood. They change quantitatively during tumour development. They can be measured using antibody techniques

Question 26

What’s the most famous serum biomarker analysis?

Answer 26

Prostate specific antigen test

Question 27

Why do we still do traditional histopathology if we have molecular pathology now?

Answer 27

The phenotypic info of histology reflects the aggregate effect of many molecular alterations on cancer cell behaviour. It can therefore give 1 rapid, convenient read out. It also provides info of aggressiveness. Molecular biology then adds to the effectiveness of prognosis and therapeutics.