laboratory diagnosis Flashcards
example of a mass screening
Pap smears for cervical cancer
example of a screening for asymptomatic patietns
PSA in men for prostate cancer
example of a screening for symptomatic patients
CA-125 for ovarian cancer
gold standars for tumor tissue biopsy
histology
biomarkers are used for
prognostic and predictive use
three identifiers preferred
yep
normal overlying mucosa makes primary adenocarcinoma very unlikely
yep
Tumor type?
Cytokeratins (CK), Epithelial Membrane Antigen (EMA)
carcinoma
tumor type?
ER, PR, GCDFP-15, GATA-3
breast
tumor type?
PSA, PSAP
prostate
tumor type?
TTF-1, Napsin A, CK7
lung adenocarcinoma
tumor type?
CDX2, CK20, CEA
colon
tumor type?
CD10, vimentin, RCC, PAX2, PAX8
kidney (renal cell carcinoma)
tumor type?
Leukocyte common antigen (CD45)
lymphoma
tumor type?
S-100, Melan-A, HMB-45, SOX-10
melanoma
tumor type?
CK, chromogranin, synaptophysin, CD56
neuroendocrine tumor
tumor type?
CK, ß-HCG, AFP, PLAP
Germ cell tumor
tumor type?
Variable and tumor-type specific
vimentin, desmin, smooth muscle actin, CD31, CD34
soft-tissue/sarcoma
Clinicopathologic correlation is essential in addition to immunohistochemistry
yep
small cell lung carcinoma:
- type of tumor
- tumor analysis needed?
- surgery?
- chemo?
- neuroendocrine carcinoma
- no further tumor analysis needed
- surgery a no go
- platinum-based chemo
tumor treatment depends on (4)
- tumor subtype
- tumor stage
- molecular testing for NSCLC
- multidisciplinary tumor conference
CK5 - , p56 - , TTF +, CK7 +, napsin A+
adenocarcinoma
CK5 + , p56 + , TTF -, CK7 -, napsin A-
squamous cell carcinoma
predictive molecular studies (4)
- DNA sequence analysis
- FiSH
- RNA-based gene expression studies
- immune checkpoint inhibition therapy
Examples in lung cancer
- DNA sequence analysis
- FiSH
- RNA-based gene expression studies
- immune checkpoint inhibition therapy
- DNA sequence analysis- EGFR mutation to predict response to tyrosine kinase inhibitors
- FiSH- EML4-ALK fusion for ALK inhibitor therapy
- RNA-based gene expression studies- potential drug targets
- immune checkpoint inhibition therapy- nivolumab: PD-L1 expression by IHC
______ is essential for further testing
tissue conservation
Tumors with specific therapies; represent _____ of CUP
10 -15%
initial IHC goal is to
broadly categorize tumor
Ck 7 -/CK 20+
colorectal and merkel cell carcinoma
Ck 7 +/CK 20+
urothelial, ovarian, and pancreatic cancer and cholangiocarcinoma
Ck 7 -/CK 20-
hepatocellular, renal cell, prostate, squamous cell
Ck 7 +/CK 20-
lung, breatm thryoid, endometrial, cervical and pancreatic carcinoma and cholangiocarcinoma
A characteristic that is objectively measured as an indicator of normal biological processes, pathogenic processes, or a pharmacological response to a therapeutic intervention.
biomarker
A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease.
biomarker
cancer biomarker prognostic
assess survival probabilities- tumor size
cancer biomarker :
predictive
effective drug therapy– ER, HER2 and KRAS
cancer biomarker :
therapeutic monitor
detect tumor recurrence– CEA
cancer biomarker:
risk stratification
chance of getting cancer- BRCA1
pT3
tumor extends into subserosal fat
Lymph nodes positive for metastatic tumor (histology)
Higher tumor stage is prognostic of poorer survival
Presence of K-ras mutation in tumor (DNA analysis)
Predicts lack of therapeutic response to a specific drug
Monitor postoperative serum CEA levels (tumor marker)
Increasing values signal tumor recurrence
Immunohistochemistry:
- Loss of expression in tumor
- May prompt DNA analysis
Microsatellite DNA Analysis
- Additional peaks in tumor
- Confirms microsatellite instability
Conclusion?
- Consider genetics consultation
2. Possible Lynch syndrome (HNPCC)
if the tumor has this mutation it will not respond to cetuximab
Kras
A substance produced by a tumor or by a host in response to the tumor’s presence.
tumor markers
clinical uses of serum tumor markers: (4)
- Screening select populations (sensitivity and specificity are variable)
- An aid in diagnosis in correlation with clinical/imaging/pathology
- Primary use: Monitor response to therapy or recurrence
- Not used for primary diagnosis
- Absence ctDNA after surgery associated with better prognosis, less chance of relapse
- Prognosis aids in selecting treatment and need for adjuvant therapy
- Patients at high risk may need targeted treatment
–Low risk patients can be spared unnecessary chemotherapy
prognosis determination
- ctDNA analyzed by blood test (liquid biopsy)
- Can be repeated for consistent monitoring of response to treatment
- Elevated ctDNA or increased number of mutations indicate treatment failure/relapse earlier than clinical relapse
monitoring treatment efficacy/relapse
- Sequencing ctDNA informs choice of therapy to target specific mutations
- Monitors intratumoral heterogeneity to refine targeted treatment
selection of treatment
- Increased ctDNA correlates with advanced tumor stage/tumor burden
- Can be repeated more often than imaging or traditional biopsies
tumor size/disease burden
- Poor sensitivity for early stage tumors
- Insufficient ctDNA to allow for an accurate test result
- ctDNA for early diagnosis and early intervention and higher cure rates
defection in asymptomatic individuals (screening)
