Dr. Nabb

Question 1

Grade of tumor

Answer 1

Low grade tumor 
Grow more slowly
More closely resemble normal tissue
Little cytologic atypia
Low mitotic rate
High grade tumors
Grow more rapidly
More cytologic atypia with pleomorphism
High mitotic rate

Question 2

CAP

Answer 2

College of American Pathologists (CAP) uses a similar pathologic schema pT pN pM (looking in a microscope)
CAP cancer protocols posted on CAP web site

Question 3

What are the molecular test for breast cancer?

Answer 3

ER/PR, HER2 (IHC, which looks at protein, and FISH, which looks at amplification), and Ki-67

These are performed on everyone.

Question 4

What is the optional test that can be performed for breast cancer?

Answer 4

Multigene panels in early stage (I or II) ER+ HER2-

Oncotype DX 21 genes typically for larger primary tumor and less differentiated) – only good for 5 years

• Higher recurrence score prognostic of greater risk of recurrence
• Higher recurrence score predictive of response to chemotherapy

ProsignaBreast CancerPrognostic Gene Signature Assay (formerly called PAM50) 50 genes - better

• Risk of recurrence (ROR) up to 10 years
• Subtype classifier

Question 5

HER2 interpretation (IHC and FISH)

Answer 5

Negative results is 0 or 1+

• 0: no staining to incomplete membrane staining and within = 10% of tumor cells
• 1+: incomplete membrane staining and >10% of tumor cells

Positive results is 3+
- uniform intense membrane staining of >10% of invasive tumor cells

If it is equivocal - repeat using IHC or ISH (FISH)

Question 6

stage of tumor

Answer 6

Extent of primary tumor (designated T) – organ linited
Size of tumor mass (breast, lung, kidney)
Depth of invasion (gastrointestinal tract)
Tumor presence or absence in lymph nodes (N) – outside of organ
Presence or absence of metastasis (M) – harder to treat

Question 7

Prognosis of low stage vs high stage tumor

Answer 7

Low stage usually organ confined with best prognosis

The higher the stage, the poorer the survival

Question 8

In the U.S, breast cancer death rates are second after?

Answer 8

Lung cancer

Question 9

At what age is breast cancer in women more common in african americans than which women?

Answer 9

Less than 45

Question 10

What is the most commonly diagnosed cancer among american women?

Answer 10

breast cancer and skin cancer

Question 11

What percent of breast cancer in women is sporadic?

Answer 11

85%

Question 12

Which of the two most common BRCA gene mutations has a higher lifetime risk?

Answer 12

BRCA1

Question 13

Which type of breast cancer tumor is estrogen receptor positive?

Answer 13

Luminal A
Luminal B
They account for 70% of breast cancer and are ER+

Question 14

Which type of breast cancer tumor is estrogen receptor negative?

Answer 14

HER2-E 15%

Basal Like 15%

Question 15

What are the characteristics of Luminal B?

Answer 15

: triple ER/PR/HER2 positive or
ER+, PR+/- and Ki-67 >14%

Has a higher proliferation than luminal A

Question 16

Interpretation of ER/PR

Answer 16

ER/PR positive: >1% nuclear expression
Report % cancer cells positive and intensity of staining (1+, 2+, 3+)

ER/PR negative: <1% nuclear expression

Question 17

Luminal Breast Cancer

Answer 17

• High hormone receptors
• LumA>LumB
• 70% of Breast cancer
• ER/PR +
• come express HER2 (LUMB)
• Respond to endocrine therapy
• Response to chemo is greater in LumB
• Prognosis is better in LumA

Question 18

HER2 Breast cancer

Answer 18

• High HER2
• LOW ER
• 15% of breast cancer
• ER/PR -
• most likely high grade and node+
• Respond to trastuzumab , anthracycline chemo
• Poor prognosis

Question 19

Basal like breast cancer

Answer 19

• high basal epithelial genes
• basal CKs
• Low ER and HER2
  15% of breast cancers
  Most ER/PR/HER2 -
  BRCA1 dysfunction (gremlin, sporadic)
• no response to endocrine or trastuzumab
• sensitive to platinum/PARP inhibitors
  POOR prognosis

Question 20

What is favorable in breast cancer?

High Yield

Answer 20

ER/PR positive
Low Ki-67
HER2 negative
Lymph nodes negative

Question 21

What is unfavorable in breast cancer?

High Yield

Answer 21

ER/PR negative
High Ki-67 >14%
HER2 positive
Lymph nodes positive
Triple negative

Question 22

What are the two pathways for colorectal cancer?

Answer 22

Chromosomal instability
3/4 of cancers

Microsatallite instability

Question 23

Chromosomal Instability of Breast Cancer

Answer 23

74% - APC-β Catenin Genes in Wnt Signaling Pathway
1% -Inherited: Familial Adenomatous Polyposis (FAP) – 100% life time risk

Progression is caused by allelic imbalance and cumulative gene mutations

Triggering mutation to carcinoma is in p53/PI#k

Question 24

Microsatallite instability

Answer 24

12% - Mismatch Repair Genes (sporadic)
Acquired hypermethylation of MLH1 promoter with gene silencing
Leads to IHC profile: MLH1/PMS2 negative
BRAF mutation (50%)

3% - Hereditary NonPolyposis Colorectal Carcinoma (HNPCC) AKA Lynch Syndrome Germline mutation in one of the mismatch repair genes (MLH1, PMS2, MSH2, MSH6)
3% of CRC
MLH1 germline mutation can have IHC profile MLH1/PMS2 negative

Question 25

What are the four mismatch repair genes?

Answer 25

MSH2, MSH6, PMS2, MLH1

Question 26

What does invasive colon carcinoma typically show?

Answer 26

gland formation with intraluminal ‘dirty’ necrosis containing neutrophils (open arrows) and cribriform ‘gland in gland’ pattern (blue arrow)

Question 27

What are the molecular test for CRC?

Answer 27

KRAS - poor prognosis and mutation predicts lack of response to anti-EGFR therapy (mutation continuously activates EGF signal)

BRAF V600 - predicts prognosis because when it occurs in a patient who has sporadic microsatallite instability that have a better prognosis. This occurs in 50% of patients. Not seen in patients with Lynch Syndrome

Mismatch Repair - identification of high risk for Lynch syndrome or prognostic stratification.. If they are MSI-H they do better at all stages. This predicts if they will respond to chemo (insensitive to cisplatin/still sensitive to oxaliplatin)