L.17 IHC Prognosis & Therapeutics Flashcards
(103 cards)
1
Q
What is Immunohistochemistry (IHC)?
A
A laboratory technique that uses antibodies to detect specific proteins in tissue samples
IHC plays a vital role in cancer diagnosis, prognosis, and guiding targeted therapies.
2
Q
What do prognostic markers in IHC provide information about?
A
The likely biological behavior of a tumour and patient outcomes
Prognostic markers help assess the aggressiveness of the cancer.
3
Q
What is Ki67?
A
A nuclear protein expressed during active phases of the cell cycle
A high Ki67 index indicates a rapidly growing, aggressive tumour.
4
Q
In which cancers is Ki67 commonly used?
A
Breast cancer, lymphomas, and neuroendocrine tumours
Ki67 is an important proliferation marker.
5
Q
What is the role of predictive (therapeutic) markers in IHC?
A
They predict response to specific treatments and guide the use of targeted therapies
These markers help in tailoring treatment plans.
6
Q
What hormone receptors are present in approximately 70-80% of breast cancers?
A
Oestrogen Receptor (ER) and Progesterone Receptor (PR)
Positive tumours respond to hormonal therapies.
7
Q
What is the function of Tamoxifen?
A
Blocks oestrogen receptors
Used in the treatment of hormone receptor-positive breast cancer.
8
Q
What do Aromatase Inhibitors do?
A
Reduce oestrogen synthesis
They are used in the treatment of hormone receptor-positive breast cancer.
9
Q
What does HER2 indicate in breast cancer?
A
Overexpression/amplification in 15-20% of invasive breast cancers
Indicates a worse prognosis but is predictive of response to Trastuzumab therapy.
10
Q
What is the significance of Mismatch Repair (MMR) Proteins in colon cancer?
A
Loss of expression indicates microsatellite instability (MSI), linked to Lynch Syndrome
Guides the use of immunotherapy.
11
Q
What does overexpression of EGFR indicate in colon cancer?
A
May indicate response to anti-EGFR antibodies (Cetuximab, Panitumumab)
This is important for targeted therapy in colon cancer.
12
Q
What does PD-L1 predict in lung cancer?
A
Response to immune checkpoint inhibitors (Pembrolizumab, Nivolumab)
PD-L1 is expressed in non-small cell lung carcinoma (NSCLC).
13
Q
How is HER2 assessed in gastric cancer?
A
To guide Trastuzumab therapy
Similar assessment as in breast cancer.
14
Q
What is the role of diagnostic biomarkers in breast cancer?
A
Used to confirm the epithelial origin and subtype of breast tumours
Key diagnostic biomarkers include Cytokeratin (CAM5.2), Epithelial Membrane Antigen (EMA), Human Milk Fat Globule (HMFG 1 & 2), and E-cadherin.
15
Q
What does the loss of E-cadherin indicate in breast cancer?
A
Indicates invasive lobular carcinoma
E-cadherin is a crucial marker for assessing tumor invasiveness.
16
Q
Which markers are associated with basal-like breast cancer?
A
EGFR, Cytokeratin 5/6
These markers help identify the basal-like subtype of breast cancer.
17
Q
What are the markers of myoepithelial cells used for?
A
Help distinguish in situ from invasive carcinoma
Key markers include Smooth Muscle Actin (SMA), Calponin, and p63.
18
Q
List the prognostic and therapeutic markers in breast cancer.
A
- Hormone Receptors (ER/PR)
- HER2
- Ki67
- p53
p53 is a tumor suppressor often mutated in aggressive tumors.
19
Q
What does a HER2 IHC score of 0 or 1+ indicate?
A
Negative, no HER2-targeted therapy
This scoring is part of the HER2 testing workflow.
20
Q
What is the significance of a HER2 IHC score of 2+?
A
Equivocal: Requires confirmatory testing
A score of 2+ does not immediately qualify for HER2-targeted therapy.
21
Q
What does a HER2 IHC score of 3+ indicate?
A
Eligible for HER2-targeted therapy (e.g., Trastuzumab)
A score of 3+ suggests strong HER2 positivity.
22
Q
What confirmatory tests are used for an equivocal HER2 IHC score?
A
- Fluorescence In Situ Hybridisation (FISH)
- Chromogenic In Situ Hybridisation (CISH or DISH)
These tests help confirm HER2 status in equivocal cases.
23
Q
What defines HER2 amplification?
A
HER2/Chromosome 17 ratio > 2.2
This ratio is used in confirmatory testing.
24
Q
What are the clinical implications of HER2 amplification?
A
Correlates with aggressive tumour biology
HER2-positive patients benefit from targeted therapies like Trastuzumab (Herceptin).
25
What must all invasive breast carcinomas be evaluated for?
Oestrogen Receptor (ER), Progesterone Receptor (PR), HER2 (ERBB2 / HER2/Neu amplification)
## Footnote
These evaluations determine suitability for targeted therapies.
26
What is the purpose of evaluating breast carcinomas for ER, PR, and HER2?
Determines suitability for targeted therapies (e.g., hormonal or anti-HER2 therapy)
## Footnote
Targeted therapies can significantly impact treatment decisions and outcomes.
27
What defines Triple-Negative Breast Cancer (TNBC)?
Lacks expression of ER, PR, and HER2 (triple-negative by immunohistochemistry - IHC)
## Footnote
This subtype poses unique challenges in treatment.
28
What are the subtypes of Triple-Negative Breast Cancer (TNBC)?
* Basal-like TNBC: Positive for CK5/6 and EGFR
* Non-basal TNBC: Negative for CK5/6 and EGFR
## Footnote
Understanding these subtypes can influence treatment strategies.
29
What remains the main therapeutic option for Triple-Negative Breast Cancer (TNBC)?
Chemotherapy
## Footnote
Unlike other breast cancer types, there are no current targeted therapies for TNBC.
30
True or False: There are targeted therapies available for Triple-Negative Breast Cancer (TNBC).
False
## Footnote
TNBC lacks targeted therapies available for hormone receptor-positive or HER2-positive cancers.
31
What is the prognosis for Triple-Negative Breast Cancer (TNBC)?
Generally worse due to limited treatment options, higher rates of recurrence and metastasis
## Footnote
The aggressive nature of TNBC contributes to its poor prognosis.
32
What does lymph node status indicate in breast cancer prognosis?
Number of positive nodes correlates with risk of recurrence and survival.
## Footnote
Lymph nodes are critical in assessing the potential spread of cancer.
33
How does tumor size affect breast cancer prognosis?
Larger tumours indicate more aggressive disease.
## Footnote
Tumor size is a key factor in determining treatment options and outcomes.
34
What are the histologic types of breast cancer and their significance?
Subtypes include ductal, lobular, mucinous, each with varying prognoses.
## Footnote
Different histologic types may respond differently to treatments.
35
What is the significance of lymphovascular invasion in breast cancer?
Presence of tumour cells in lymphatic or vascular channels worsens prognosis.
## Footnote
Lymphovascular invasion suggests a higher likelihood of metastasis.
36
What is the role of hormone receptor status in breast cancer treatment?
ER/PR positive tumours respond well to hormonal therapies (Tamoxifen, Aromatase Inhibitors).
## Footnote
Hormone receptor status guides the use of targeted therapies.
37
What does HER2 amplification indicate in breast cancer?
Associated with aggressive disease but targetable with HER2 therapies (Trastuzumab).
## Footnote
HER2-positive cancers often require specific treatment strategies.
38
What does a high proliferation index (Ki67) indicate?
High Ki67 labelling indicates rapid tumour cell proliferation and poor prognosis.
## Footnote
Ki67 is often used as a marker for cancer aggressiveness.
39
What is the TNM classification for Tis in breast cancer staging?
Carcinoma in situ.
## Footnote
Tis indicates that cancer cells are present but have not invaded surrounding tissues.
40
What does T1 indicate in breast cancer staging?
Tumour confined to breast, <2 cm.
## Footnote
T1 signifies an early stage of breast cancer with a generally better prognosis.
41
What does T4 indicate in breast cancer staging?
Tumour extends beyond breast tissue (e.g., skin, chest wall involvement).
## Footnote
T4 is associated with more advanced disease and worse outcomes.
42
What are the routes of metastatic spread in breast cancer?
Local Invasion, Lymphatic Spread, Hematogenous (Blood) Spread.
## Footnote
Understanding these routes is essential for treatment planning and prognosis.
43
What is an example of local invasion in breast cancer?
Skin, nipple, chest wall.
## Footnote
Local invasion can lead to more complex treatment needs.
44
What is an example of hematogenous spread in breast cancer?
Lungs, liver, bones, serous cavities (pleura, peritoneum).
## Footnote
Hematogenous spread indicates advanced disease and can complicate treatment.
45
What factors are treatment individualized based on?
* Age.
* Hormone receptor status (ER/PR).
* HER2 amplification status.
* Lymph node involvement.
## Footnote
These factors influence the choice of therapy for patients.
46
What are the main treatment modalities for cancer?
* Hormonal Therapy: Tamoxifen, Aromatase inhibitors.
* Chemotherapy: For aggressive or triple-negative cases.
* HER2-Targeted Therapy: Trastuzumab (Herceptin).
* Adjuvant Radiotherapy: Post-surgical local control.
## Footnote
Each modality targets different aspects of cancer treatment.
47
What are the side effects of Tamoxifen?
* Alters calcium metabolism.
* Increased risk of endometrial cancer.
## Footnote
Patients should be monitored for these side effects.
48
What is a side effect of Trastuzumab (Herceptin)?
Risk of cardiotoxicity (requires cardiac monitoring).
## Footnote
It is essential to monitor heart health during treatment.
49
True or False: Long-term survival for aggressive cancers is declining due to late detection.
False.
## Footnote
Long-term survival is improving due to early detection and better therapeutic strategies.
50
What are the diagnostic methods for Gastric Adenocarcinoma?
* Endoscopy.
* Biopsy.
* Histopathology.
## Footnote
These methods are crucial for accurate diagnosis.
51
What are the immunohistochemistry (IHC) biomarkers for Gastric Adenocarcinoma?
* Cytokeratin 7: Negative.
* Cytokeratin 20: Positive.
* Carcinoembryonic Antigen (CEA): Often elevated.
## Footnote
These biomarkers aid in diagnosing gastric adenocarcinoma.
52
What is the therapeutic marker for Gastric Adenocarcinoma?
HER2 (ERBB2) amplification in ~20% of cases.
## Footnote
HER2-positive tumors are treated with Trastuzumab (Herceptin).
53
What percentage of gastric tumors are gastric lymphomas?
3%.
## Footnote
Gastric lymphomas represent a small subset of gastric tumors.
54
What are the diagnostic markers for gastric lymphomas?
* CD45: General leukocyte marker (all lymphomas).
* CD20: B-cell marker.
* CD3: T-cell marker.
## Footnote
These markers help differentiate types of lymphomas.
55
What type of therapy is used for B-cell lymphomas?
Anti-CD20 monoclonal antibody therapy (e.g., Rituximab).
## Footnote
Rituximab targets CD20 on B-cells.
56
What are the diagnostic markers for Gastrointestinal Stromal Tumours (GISTs)?
* CD117 (C-Kit): Highly sensitive marker.
* DOG1: Specific for GIST.
* Vimentin: Mesenchymal marker.
## Footnote
These markers are essential for diagnosing GISTs.
57
What targeted therapy is used for GISTs?
Imatinib (Gleevec): A tyrosine kinase inhibitor targeting C-Kit.
## Footnote
Imatinib is effective in treating GISTs due to its mechanism of action.
58
What is the significance of Cytokeratin 20 (CK20) in colorectal cancer diagnosis?
Positive result helps differentiate CRC from other adenocarcinomas
## Footnote
CK20 is typically positive in colorectal cancer and negative in others like gastric, pancreatic, and lung cancers.
59
What does a positive Cytokeratin 7 (CK7) result indicate in colorectal cancer?
Negative result helps differentiate CRC from other adenocarcinomas
## Footnote
CK7 is usually negative in colorectal cancer, aiding in differential diagnosis.
60
What is Carcinoembryonic Antigen (CEA) and its relevance in colorectal cancer?
Glycoprotein involved in cell adhesion, elevated in most colorectal adenocarcinomas
## Footnote
CEA is used as a diagnostic and monitoring biomarker.
61
What is CA19.9 and its association with colorectal cancer?
Often elevated in advanced colorectal cancers and pancreaticobiliary malignancies
## Footnote
CA19.9 can indicate disease progression.
62
What are the therapeutic biomarkers used for targeted therapy selection in colorectal cancer?
EGFR & VEGFR pathways, RAS mutation status, BRAF mutation, HER2 amplification
## Footnote
These biomarkers guide the selection of appropriate targeted therapies.
63
What role do monoclonal antibodies play in colorectal cancer treatment?
Target EGFR pathways (e.g., Cetuximab, Panitumumab)
## Footnote
They are essential in the therapeutic approach for eligible patients.
64
What does RAS mutation status indicate for colorectal cancer treatment?
Predicts resistance to anti-EGFR therapy; mutated status means anti-EGFR agents are ineffective
## Footnote
RAS wild-type is essential for EGFR therapy eligibility.
65
What is the significance of the BRAF V600E mutation in colorectal cancer?
Indicates a more aggressive tumor and may guide towards BRAF-targeted therapies
## Footnote
Example of a targeted therapy is Encorafenib.
66
What does HER2 amplification signify in colorectal cancer?
Potential for anti-HER2 therapies in selected cases
## Footnote
HER2 amplification is present in a small subset of colorectal cancers.
67
What is the primary biomarker used for monitoring treatment response in colorectal cancer?
Carcinoembryonic Antigen (CEA)
## Footnote
CEA is crucial for detecting recurrence.
68
What additional biomarker can be used alongside CEA for monitoring advanced colorectal cancer?
CA19.9
## Footnote
CA19.9 provides complementary information in monitoring.
69
What are common sites for melanoma in females and males?
Females: Legs; Males: Trunk
## Footnote
This reflects typical patterns of melanoma occurrence.
70
What are the main risk factors for developing melanoma?
Chronic sun exposure, use of sunbeds, pre-existing moles
## Footnote
These factors increase the risk of melanoma transformation.
71
List the types of melanoma.
* Superficial spreading
* Nodular
* Amelanotic
## Footnote
Each type has different characteristics and behaviors.
72
What is the gold standard for melanoma diagnosis?
Excision Biopsy
## Footnote
This method is crucial for definitive diagnosis.
73
What is the role of Fine Needle Aspiration (FNA) in melanoma diagnosis?
Used for sampling metastatic sites
## Footnote
Commonly targets lymph nodes and organs.
74
What are some prevention strategies for melanoma?
* Regular use of sunscreen
* Protective clothing
* Early life UV protection
* Avoidance of sunbeds
* Self-monitoring of moles
## Footnote
These strategies help reduce the risk of melanoma development.
75
What should individuals self-monitor in moles for signs of melanoma?
* Changes in size
* Changes in shape
* Changes in colour
* Changes in texture
* Signs of ulceration, bleeding, redness (ABCDE criteria)
## Footnote
Monitoring for these changes can lead to early detection.
76
What is the use of the marker Melan-A?
Diagnostic for melanoma cells
## Footnote
Melan-A is specifically used to identify melanoma cells in diagnostic settings.
77
What does the marker S100 indicate?
Sensitive marker for melanocytic lineage
## Footnote
S100 is used to determine the lineage of melanocytic cells.
78
What is HMB45 used for?
Diagnostic for melanoma, especially in metastases
## Footnote
HMB45 is particularly effective in identifying melanoma in metastatic cases.
79
What is the significance of the SOX10 marker?
Highly sensitive for melanoma, including metastatic lesions
## Footnote
SOX10 is a crucial marker for diagnosing melanoma and its spread.
80
What does PRAME stand for?
A newer marker for melanoma diagnosis and prognosis
## Footnote
PRAME is utilized in both diagnosing melanoma and predicting its progression.
81
What is the predictive marker for targeted therapy in melanoma?
BRAF V600E Mutation
## Footnote
The BRAF V600E mutation is key for determining eligibility for BRAF inhibitors.
82
What percentage of melanomas harbor BRAF V600E mutations?
50–60%
## Footnote
This mutation is one of the most common in melanoma cases.
83
What is the mechanism of action of BRAF inhibitors like Vemurafenib?
Targeting BRAF V600E mutations
## Footnote
BRAF inhibitors specifically target the mutated BRAF protein to inhibit cancer cell growth.
84
What is the most common mutation in the BRAF gene?
V600E
## Footnote
The V600E mutation results from a substitution at codon 600.
85
What does the BRAF gene encode?
A serine/threonine-protein kinase
## Footnote
This kinase is involved in the MAPK/ERK signaling pathway, essential for cell growth.
86
What are the therapeutic agents often combined with BRAF inhibitors?
MEK inhibitors
## Footnote
Combining BRAF inhibitors with MEK inhibitors can improve treatment response and delay resistance.
87
What are some mechanisms of resistance to BRAF inhibitors?
* Secondary mutations activating bypass pathways
* Upregulation of alternative signaling routes
## Footnote
These mechanisms can lead to treatment failure in some patients.
88
True or False: All patients with BRAF mutations respond to BRAF inhibitors.
False
## Footnote
Not all patients respond, and even those who do can develop resistance.
89
What leads to uncontrolled cell proliferation in melanoma with BRAF mutations?
Constitutive activation of BRAF kinase
## Footnote
This activation occurs due to the V600E mutation in the BRAF gene.
90
Fill in the blank: The BRAF gene mutation analysis is crucial for identifying _______.
likely responders to BRAF inhibitors
## Footnote
This analysis is essential for tailoring targeted therapies.
91
What are the two major histological types of lung cancer?
Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC)
## Footnote
NSCLC accounts for approximately 85% of lung cancer cases.
92
How is Non-Small Cell Lung Cancer (NSCLC) further classified?
Based on molecular alterations, especially important in non-smokers
## Footnote
Molecular alterations can indicate specific treatment options.
93
What is the predictive mutation for therapy in NSCLC associated with EGFR Exon 19 deletions?
Respond to EGFR-TKIs (Gefitinib, Erlotinib, Afatinib)
## Footnote
EGFR-TKIs are a class of drugs targeting the EGFR mutation.
94
What mutation is associated with resistance to first-generation EGFR-TKIs?
T790M Mutation
## Footnote
Sensitive to third-generation TKI (Osimertinib).
95
Name two first/second generation EGFR Tyrosine Kinase Inhibitors (TKIs).
Gefitinib and Erlotinib
## Footnote
These TKIs improve response rates and overall survival for NSCLC patients.
96
What is the typical duration before disease progression occurs after initial EGFR-TKI therapy?
10-14 months
## Footnote
Resistance typically develops after this period.
97
What is the most common resistance mechanism in NSCLC?
T790M Mutation
## Footnote
Accounts for 30-50% of acquired resistance cases.
98
What are the detection challenges associated with resistance mutations?
Repeat tissue biopsy is invasive; liquid biopsy is a less invasive alternative
## Footnote
Liquid biopsy can identify circulating tumor DNA.
99
What does the third-generation TKI Osimertinib specifically target?
T790M mutation
## Footnote
Approved for T790M-positive NSCLC patients with acquired resistance.
100
What emerging resistance mutations can confer resistance to Osimertinib?
L718V and C797S
## Footnote
These mutations require novel or combination therapies.
101
What is essential upon disease progression in NSCLC treatment?
Repeat testing of mutation profile
## Footnote
This is crucial for tailoring treatment strategies.
102
Future therapies for NSCLC may involve what type of regimens?
Combination regimens targeting multiple pathways
## Footnote
These may improve treatment outcomes.
103
Fill in the blank: EGFR Exon 21 (L858R) responds to _______.
EGFR-TKIs (Gefitinib, Erlotinib, Afatinib)
## Footnote
This mutation is also predictive for therapy.
