Tumour histopathological

subtyping, grading,
staging and prognosis

Week 3: Lecture 1

BMS850_W2023
Dr. Michael Olson
 Key points from last lecture

• Cancer significantly impacts our society

• Cancer is a collection of diseases
• Cancer begins when normal cells undergo genetic changes
and start growing uncontrollably
• Cancer is detected using imaging techniques
• Cancer is diagnosed using histopathology techniques
• Cancer develops in stages over a long period of time
• Cancer is caused by exposure to risk factors
• Carcinogens are directly involved in causing cancer
• All mutagens are carcinogens
• Majority of cancers are due to lifestyle and are preventable

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Histopathological subtyping
of tumours

Sources:
Robert Weinberg: The Biology of Cancer – Chapter 2
Lewis J. Kleinsmith: Principles of Cancer Biology
 Tumour specific markers

• Tumour markers are molecules that are

considered as signals of tumour cells and are
altered in cancerous conditions.
– Proteins, DNA, gene expression patterns
• One specific kind of cancer is normally
characterized by one or more tumour markers.
– Used for tumour subtyping
• Expression of tumour specific markers is used
for cancer diagnosis, prognosis and guiding
treatment.
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 Immunohistochemistry (IHC)

• IHC is a histopathological technique that uses specific antibodies

that detect specific tumour markers on tissue sections.

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 Immunohistochemistry principle
Labeling reaction

https://www.proteinatlas.org/learn/method/immunohistochemistry

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Immunohistochemistry principle
Detecting signal (chromogen staining)

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Epithelial cells
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Stroma cells http://www.pathologyoutlines.com/topic/stainsttf1.html
Example 1: Lung Carcinoma

TTF marker

Lung Adenocarcinoma

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Example 1: Lung Carcinoma

p63 marker

Squamous Carcinoma 10
Example 2: Breast Carcinoma

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Ductal vs. lobular breast carcinoma

CK903

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Invasive lobular carcinoma
 Ductal vs. lobular breast carcinoma

CK8 CK8

Invasive lobular carcinoma Invasive ductal carcinoma 13

Yeh et al. 2008 Arch Pathol Lab Med – Vol 132.
 Tumour Grade

Sources:
National Cancer Institute: Prognosis
 Tumour Grading

• The description of a tumour based on how

abnormal the tumour tissue looks under
microscope.
– If the organization of the tumour tissue is close to those
of normal cells and tissue, the tumour is well‐
differentiated.
– If the organization of the tumour tissue lack normal
tissue structures, the tumour is undifferentiated or
poorly differentiated.
• Tumour grade is an indicator of tumour
aggressiveness (how quickly a tumour is likely to
grow and spread).
– Less differentiated tumours are more aggressive 15
 Tumour Grading

• Grading systems differ depending on the type of cancer.

• Generalized grading: 1, 2, 3, 4 depending on the level of
abnormality
– Grade 1 = close to normal; slow growing
– Grade 4 = no resemblance to normal; fast growing

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 Tumour Grading

• Some cancers have their own grading systems

– Example: Breast Cancer Scoring system
• Features:
– Tubule Formation: how much of the tumour has normal breast milk duct structures.
– Nuclear grade: an evaluation of the size and shape of the nucleus in the tumour cells.
– Mitotic rate: how many dividing cells are present.
• Scoring:
– G1: (Low grade/Well Differentiated)
– G2: (Intermediate grade/Moderately Differentiated)
– G3: (High grade/Poorly Differentiated)

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 Breast carcinoma

Low grade High grade

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http://pathology.jhu.edu/breast/grade.php
 Cancer Staging

Sources:
National Cancer Institute: Cancer Staging
 Cancer Staging

• Estimates how far a person’s cancer has progressed at the time of

diagnosis.
• Description of how large a tumour has grown and how far it has
spread.
• TNM system
– T=tumour size
– N=lymph node
– M=metastasis

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 TNM Staging System

Primary tumor (T)

TX: Main tumor cannot be measured.
T0: Main tumor cannot be found.
T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after
the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further
divided to provide more detail, such as T3a and T3b.

Regional lymph nodes (N)

NX: Cancer in nearby lymph nodes cannot be measured.
N0: There is no cancer in nearby lymph nodes.
N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher
the number after the N, the more lymph nodes that contain cancer.

Distant metastasis (M)

MX: Metastasis cannot be measured.
M0: Cancer has not spread to other parts of the body.
M1: Cancer has spread to other parts of the body.
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 Simpler version of cancer staging

Stage 0 = Abnormal cells are present but have not spread

to nearby tissue. Also called carcinoma in situ, or CIS. CIS
is not cancer, but it may become cancer.

Stage I, Stage II, and Stage III = Cancer is present. The

higher the number, the larger the cancer tumor and the
more it has spread into nearby tissues.

Stage IV=The cancer has spread to distant parts of the

body.

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 Cancer Prognosis

Sources:
 Standard prognostic factors

• Histological subtype
• Tumour stage
• Tumour size
• Tumour grade
• Age

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 Cancer survival

• Prognosis is estimated by cancer statistics:

– Relative survival (RS)
• Percentage of cancer patients who have survived for a
certain period of time after diagnosis compared to
people who do not have cancer.
– Overall survival (OS)
• Percentage of people with a specific type and stage of
cancer who have not died from any cause during a
certain period of time after diagnosis.
– Disease‐free survival (DFS)
• Percentage of patients who have no signs of cancer
during a certain period of time after treatment.
– Also called recurrence‐free or progression‐free survival

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 Kaplan‐Meier survival analysis

• Measures endpoint outcome

– OS = death
– PFS = progression
• Cumulative probability of
surviving a given time.
• Horizontal lines = survival
duration for that interval.
• Vertical distances = change
in the cumulative probability.

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Rich et al. 2014 Otolaryngol Head Neck Surg 2010 Vol143