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)