Dr. Nabb Flashcards
Grade of tumor
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
CAP
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
What are the molecular test for breast cancer?
ER/PR, HER2 (IHC, which looks at protein, and FISH, which looks at amplification), and Ki-67
These are performed on everyone.
What is the optional test that can be performed for breast cancer?
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
HER2 interpretation (IHC and FISH)
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)
stage of tumor
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
Prognosis of low stage vs high stage tumor
Low stage usually organ confined with best prognosis
The higher the stage, the poorer the survival
In the U.S, breast cancer death rates are second after?
Lung cancer
At what age is breast cancer in women more common in african americans than which women?
Less than 45
What is the most commonly diagnosed cancer among american women?
breast cancer and skin cancer
What percent of breast cancer in women is sporadic?
85%
Which of the two most common BRCA gene mutations has a higher lifetime risk?
BRCA1
Which type of breast cancer tumor is estrogen receptor positive?
Luminal A
Luminal B
They account for 70% of breast cancer and are ER+
Which type of breast cancer tumor is estrogen receptor negative?
HER2-E 15%
Basal Like 15%
What are the characteristics of Luminal B?
: triple ER/PR/HER2 positive or
ER+, PR+/- and Ki-67 >14%
Has a higher proliferation than luminal A
Interpretation of ER/PR
ER/PR positive: >1% nuclear expression
Report % cancer cells positive and intensity of staining (1+, 2+, 3+)
ER/PR negative: <1% nuclear expression
Luminal Breast Cancer
- 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
HER2 Breast cancer
- High HER2
- LOW ER
- 15% of breast cancer
- ER/PR -
- most likely high grade and node+
- Respond to trastuzumab , anthracycline chemo
- Poor prognosis
Basal like breast cancer
- 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
What is favorable in breast cancer?
High Yield
ER/PR positive
Low Ki-67
HER2 negative
Lymph nodes negative
What is unfavorable in breast cancer?
High Yield
ER/PR negative High Ki-67 >14% HER2 positive Lymph nodes positive Triple negative
What are the two pathways for colorectal cancer?
Chromosomal instability
3/4 of cancers
Microsatallite instability
Chromosomal Instability of Breast Cancer
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
Microsatallite instability
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
What are the four mismatch repair genes?
MSH2, MSH6, PMS2, MLH1
What does invasive colon carcinoma typically show?
gland formation with intraluminal ‘dirty’ necrosis containing neutrophils (open arrows) and cribriform ‘gland in gland’ pattern (blue arrow)
What are the molecular test for CRC?
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)
