Tumor Staging, Tumor Grade, and Tumor Markers

What is the grading system used for breast cancer?

Nottingham grading system "Elston-Ellis modification of the Scarff-Bloom-Richardson grading system"

BRCA1 and BRCA2 gene mutations

Ovarian cancer Tissue analyzed: blood Determine whether treatment with targeted therapy is apporpriate

CA-125

Ovarian cancer Tissue analyzed: blood Diagnosis, assessment of response to treatment, evaluation of recurrence

HE4

Ovarian cancer Tissue analyzed: blood Plan cancer treatment, assess disease progression, monitor recurrence

CA19-9

Pancreatic cancer, gallbladder cancer, bile duct cancer, gastric cancer Tissue analyzed: blood Assess whether treatment is working

How is stage determined?

Physical exam Imaging tests Pathology report Surgical report Laboratory tests

G3

Poorly differentiated (high grade)

N1, N2, N3

Refers to number and location of lymph nodes that contain cancer Higher the number = more lymph nodes that contain cancer

Gleason X

Score cannot be determined

How is the total score calculated?

Scores for the three categories are added yielding a total score of 3 to 9

CA15-5/CA27.29

Breast cancer Tissue analyzed: blood Assess whether treatment is working or disease has recurred

What makes tumor markers?

Normal cells and cancer cells Produced at higher levels in cancerous conditions

What is the most widely used cancer staging system?

TNM staging system

Primary tumor (T)

TX T0 T1, T2, T3, T4

Chromogranin A (CgA)

Neuroendocrine tumors Tissue analyzed: blood Diagnosis, assessment of treatment response, evaluation of recurrence

Secondary pattern

Next most common pattern

Does NCI have guidelines for the use of tumor markers?

No

Is tumor grade the same as the stage?

No Stage = size/extent of original tumor and whether or not cancer cells have spread

To what does "stage" refer?

1) Extent of cancer 2) How large the tumor is 3) If it has spread

How does knowing the stage help doctors?

1) Helps understand severity of cancer and chances of survival 2) Helps plan the best treatment 3) Helps identify clinical trials that may be treatment options

Factors affecting stage

1) Location of primary tumor 2) Tumor size 3) Regional lymph node involvement 4) Number of tumors present

Limitations to use of tumor markers

1) Noncancerous conditions can cause levels to increase 2) Not everyone with a particular type of cancer will have high levels of tumor markers 3) Tumor markers have not been identified for every type of cancer

How is tumor grade determined?

1) Suspected malignant tumor removed during biopsy 2) Pathologist examines tissue to determine whether benign or malignant 3) Pathologist determines tumor grade and identifies other characteristics

How are breast tumors graded?

1) Tubule formation: how much of the tumor tissue has normal breast (milk) duct structures 2) Nuclear grade: evaluation of size/shape of nucleus in tumor cells 3) Mitotic rate: how many dividing cells are present; measure of how fast tumor cells are growing/dividing

Information included in most staging systems

1) Where tumor is located in the body 2) Cell type: adenocarcinoma, SCC 3) Size of tumor 4) Whether cancer has spread to nearby LN 5) Whether cancer has spread to different part of the body 6) Tumor grade: how abnormal the cancer cells look, how likely tumor is to grow/spread

What are the most common types of cancer with their own grading systems?

Breast Prostate

In situ

Abnormal cells are present but have not spread to nearby tissue

Stage 0

Abnormal cells are present but have not spread to nearby tissue Carcinoma in situ (CIS)

Undifferentiated and poorly differentiated

Abnormal looking cells May lack normal tissue structures

How are the categories scored?

Between 1 and 3 1 = cells/tumor tissue look most like normal cells/tissue 3 = cells/tissue look the most abnormal

On what is the Gleason score based?

Biopsy samples How similar the tumor tissue looks to normal prostate tissue

Fibrin/fibrinogen

Bladder cancer Tissue analyzed: urine Monitor progression, response to treatment

Chromosomes 3, 7, 17, 9p21

Bladder cancer Tissue analyzed: urine Monitoring for tumor recurrence

Where can tumor markers be found?

Blood, urine, stool, tumor tissue, bodily fluids

Cancers with different staging systems

Brain and spinal cord tumors Blood cancers

Estrogen receptor (ER)/progesterone receptor (PR)

Breast cancer Tissue analyzed: tumor Determine whether treatment with hormone therapy and some targeted therapies is appropriate

M0

Cancer has not spread to other parts of the body

What is metastasis?

Cancer has spread from primary tumor to other parts of the body

Distant

Cancer has spread to distant parts of the body

Stage IV

Cancer has spread to distant parts of the body

Regional

Cancer has spread to nearby lymph nodes, tissues, or organs

M1

Cancer has spread to other parts of the body

NX

Cancer in nearby lymph nodes cannot be measured

Localized

Cancer is limited to the place where it started, with no sign that it has spread

Stage I, Stage II, Stage III

Cancer is present Higher the number = larger the cancer tumor and more it has spread into nearby tissues

Grade 3, 4

Cells and tissue do not look like normal cells/tissue Grow rapidly and spread faster than tumors with lower grade

Well-differentiated

Cells of the tumor and organization of tissue are close to those of normal cells/tissue Grow and spread at a slower rate than undifferentiated/poorly differentiated

Beta-human chorionic gonadotropin (beta-hCG)

Choriocarcinoma, germ cell tumors Tissue analyzed: urine, blood Assess stage, prognosis, and response to treatment

BCR-ABL fusion gene (Philadelphia chromosome)

Chronic myeloid leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia Tissue analyzed: blood, bone marrow Confirm diagnosis, predict response to targeted therapy, monitor disease status

Carcinoembryonic antigen (CEA)

Colorectal cancer Tissue analyzed: blood Keep track of how cell treatments are working, check recurrence

BRAF V600 mutations

Cutaneous melanoma, colorectal cancer Tissue analyzed: tumor Select patients most likely to benefit from treatment with targeted therapies

What is tumor grade?

Description (numerical grade) of a tumor based on how abnormal the tumor cells/tissue look under a microscope

ALK gene rearrangements and overexpression

Non-small cell lung cancer, anaplastic large cell lymphoma Tissue analyzed: tumor Determine treatment, prognosis

How does tumor grade affect patient's treatment options?

Doctors use grade to develop a treatment plan and determine patient's prognosis Lower grade = better prognosis Higher grade = cancer may grow and spread more quickly, require immediate/more aggressive treatment

C-kit/CD117

Gastrointestinal stromal tumor, mucosal melanoma Tissue analyzed: tumor Diagnosis and determining treatment

Categories of Gleason score

Gleason X Gleason 2-6 Gleason 7 Gleason 8-10

What is the grading system used for prostate cancer?

Gleason scoring system

GX

Grade cannot be assessed (undetermined grade)

How are tumor grades classified?

Graded as 1, 2, 3, 4 depending on amount of abnormality

How are each patterns graded?

Graded from 1 to 5 1 = most like normal prostate tissue 5 = looks the most abnormal

Five main categories of cancer

In situ Localized Regional Distant Unknown

What does tumor grade indicate?

It is an indicator of how quickly a tumor is likely to grow and spread

Does the stage change if the cancer changes?

No, a cancer is always referred by the stage it was given at diagnosis even if it gets worse or spreads New information gets added on to original stage

Is carcinoma in situ cancer?

No, but it may become cancer

CD20

Non-Hodgkin lymphoma Tissue analyzed: blood Determine whether treatment with targeted therapy is appropriate

EGFR gene mutation analysis

Non-small cell lung cancer Tissue analyzed: tumor Determine treatment, prognosis

Prognosis

Likely outcome or course of a disease Chance of recovery or recurrence

Alpha-fetoprotein (AFP)

Liver cancer, germ cell tumors Tissue analyzed: blood Diagnose liver cancer, follow response to treatment Assess stage, prognosis, and response to treatment of germ cell tumors

Cytokeratin fragment 21-1

Lung cancer Tissue analyzed: blood Monitoring for recurrence

TN(M)

M = whether cancer has metastasized

Distant metastasis (M)

MX M0 M1

T0

Main tumor cannot be found

TX

Main tumor cannot be measured

How can tumor markers be used in treatment?

Measured periodically during therapy Decrease in level or return to normal level may indicate that cancer is responding to treatment

Calcitonin

Medullary thyroid cancer Tissue analyzed: blood Diagnosis, check whether treatment is working, assess recurrence

MX

Metastasis cannot be measured

Circulating tumor cells of epithelial origin (CELLSEARCH)

Metastatic breast, prostate, colorectal cancers Tissue analyzed: blood Inform clinical decision making, assess prognosis

G2

Moderately differentiated (intermediate grade)

Primary pattern

Most common tissue pattern seen in the tumor

When are the five main categories used?

Most often used by cancer registries than by doctors

Beta-2-microglobulin (B2M)

Multiple myeloma, chronic lymphocytic leukemia, some lymphomas Tissue analyzed: blood, urine, CSF Determine prognosis and follow response to treatment

T(N)M

N = number of nearby lymph nodes that have cancer

Regional lymph nodes (N)

NX N0 N1, N2, N3

T1, T2, T3, T4

Size and/or extent of main tumor Higher the number = larger tumor or more it has grown into nearby tissues

For which types of cancer is tumor grade most important in planning treatment and determining prognosis?

Soft tissue sarcoma Primary brain tumors Breast and prostate cancer

Five less-detailed stages of cancer

Stage 0, I, II, III, IV

What are tumor markers?

Substances that are produced by cancer or by other cells of the body in response to cancer or certain benign conditions Most are proteins Can be patterns of gene expression and changes to DNA

(T)NM

T = size and extent of main/primary tumor

How is the Gleason score calculated?

The two pattern grades are added

N0

There is no cancer in nearby lymph nodes

Unknown

There is not enough information to figure out the stage

What are the three grades possible for breast cancer?

Total score = 3-5: G1 (low grade, well differentiated) Total score = 6-7: G2 (intermediate grade, moderately differentiated) Total score 8-9: G3 (high grade, poorly differentiated)

Grade 1

Tumor cells and organization of tissue appear close to normal Grow and spread slowly

Gleason 7

Tumor tissue is moderately differentiated

Gleason 8-10

Tumor tissue is poorly differentiated or undifferentiated

Gleason 2-6

Tumor tissue is well differentiated

How are tumor markers measured?

Tumor tissue or bodily fluid Serial measurements for treatment response

G4

Undifferentiated (high grade)

How are tumor markers used?

Used to help detect, diagnose, and manage cancer Can be used to check for recurrence

G1

Well-differentiated (low grade)