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CCHM TUMOR MARKERS Flashcards

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1
Q

Major Processes Involved in Cell Growth

A

Proliferation
Differentiation

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2
Q

Formation of solid mass or tumor
Activation of ___ eg. ___
Activation of ____ (___),
Inhibition of ____, ___ and ____ (eg___)

A

Tumorigenesis
- growth factors (e.g., epidermal growth factor [EGF])
- oncogenes e.g., K-ras
-apoptosis
- tumor suppressor
cell cycle regulation genes (e.g., BRCA1, p53, cyclins)

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3
Q

Involves the multiplication of cells in an organ or tissue, which may consequently have _____ in volume.
Serves a useful purpose and is controlled by ____
Elevation of tumor markers is _____.

A

Hyperplasia
-increased
- stimuli
- transient

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4
Q

Tumors remain at the primary site and present a smaller risk to the host
At this stage the patient stands a good chance of being successfully treated by the complete removal of the tumor.
Early detection is critical to ___ prevention in general to high risk families in particular
Well differentiated and composed of cells resembling the nature of normal cells from the tissue of origin of the ____.

A

Benign
- cancer
- neoplasm

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5
Q

Involves the possibility of normal cells undergoing cancerous proliferation
Pathologic hyperplasia
Unregulated and serves no purpose
Elevation of tumor markers will be a___ phenomenon if not treated

A

Neoplasia
- long lasting

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6
Q

Due to genetic instability of tumor cells.

A

Malignant

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7
Q

____ malignancy that begins in the skin or in tissues that line or cover internal organs

A

Carcinoma

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8
Q

malignancy that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue

A

Sarcoma

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9
Q

malignancy that begins in blood-forming tissue, such as the ___> causes too many abnormal blood cells to be made

A

Leukemia
- bone marrow

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10
Q

malignancies that begin in the cells of the immune system

A

Lymphoma and multiple myeloma

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11
Q

refers to the uncontrolled growth of cells that can develop into a solid mass or tumor and spread to other areas of the body

A

cancer

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12
Q

Cause of the most cancer deaths
Due to multiple genetic changes that result to uncontrolled proliferation
Multistep processes involving numerous tumor cell-host cell and cell-matrix interactions
___ at the primary site penetrate their adjacent surroundings (epithelial basement membrane and the interstitial stroma.)
> invade ____ or ____ to distant sites
> venous/capillary beds or solid tissue of a distant organ.
It is a ___ selective process.

A

Metastasis
- Tumor cells
- blood or lymphatic vessels
- highly

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13
Q

Controls both ___ and __
Orderly and specific transmission of growth-regulatory messages from outside the cell to the machinery controlling replication inside the cell nucleus.

A

Signal Transduction Pathway
cell cycle and apoptosis

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14
Q

It involves the passage of a cell through a complete round of ___.
It is one of the most important determining factors controlling cell proliferation.

A

Cell Cycle
- replication

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15
Q

In most mammalian cells, the cell cycle is composed of ____, ___, ____, and ___

A

four phases:
G1, S, G2, M or Mitosis, Go

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16
Q

defined as the interval between the conclusion of mitosis and start of DNA replication

A

G1

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17
Q

– interval during which the nuclear genome is replicated

A

s

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18
Q

interval between completion of DNA replication and the onset of mitosis.

A

G2

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19
Q

fifth phase – metabolic compartment of reversibly quiescent cells occupy

A

Go

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20
Q

Encoded by a separate category of genes  when mutated, will not only increase genetic instability but also ____ cellular evolution and the progression to ___.
___ is result from the absence of certain cell cycle controls
Defects in the cell cycle machinery may help cause ___.

A

Cell Cycle
- accelerate
- malignancy
- Tumors
- cancer

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21
Q

A programmed cell or physiologic death
It is a natural self-destruct system present in all cells
Failure of cells to undergo ____ may lead to cancer.
It is the natural process the body  replacement of cells and the deletion of damaged cells inherent to normal functioning of multicellular microorganism.

A

Apoptosis
- apoptotic cell death

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22
Q

It is a control mechanism for _____ and ___
Provides a way for the body to eliminate cells that have been produced in excess, that have developed improperly, or that have sustained genetic damage.

A

Apoptosis
tissue remodeling during growth development.

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23
Q

Apoptosis Markers: ____, ___, and ____
They can be both inducers and inhibitors of cell-death
These markers would have tremendous potential for ___, ____ and ___

A

p53 protein, Bcl 2, and Fas/Fas ligand
diagnosis,
prognosis
therapeutic application

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24
Q

New blood vessels are formed. Tumor growth and metastasis are _____.
It is critical, not only for the growth of solid tumors, but also for the shedding of cells from the primary tumor and the development of metastases at distant sites.
The new blood vessels embedded in a tumor provide a gateway for tumor cells to enter the circulation and to metastasize to distant sites

A

Angiogenesis
- angiogenesis-dependent

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25
The degree of it is an initial primary tumor correlates with metastatic spread and survival rates in patients Assessment may, therefore, prove valuable in selecting patients with ___for aggressive therapy.
Angiogenesis - early breast carcinoma
26
Most well known angiogenic factors: ___, ___ and ___
Vascular endothelial growth factor (VEGF) Acidic and basic fibroblast growth factor (aFGF and bFGF) Transforming growth factor alpha (TGF-alpha)
27
These are specific class of transmembrane glycoprotein involved whenever cells are ____ and __ They regulate the migration of ___ to sites of inflammation or into lymphatic tissue
Adhesion -moving - interacting - leukocytes
28
Increasing evidence has shown that the appearance of certain membrane molecules is related to metastatic potential or a sign of the conversion of normal to ___
Adhesion - malignant cells.
29
Three classes of adhesions: ___, ___ and ___
Selectins Integrins Immunoglobulin family
30
Cancer Progression
Metastasis Loss of cell adhesion proteins (e.g., β-catenin and E-cadherin) Activation of angiogenesis genes (e.g., VEGF)
31
Cancer Progression
Activation of oncogenes Upregulation of proteases Deactivation of adhesion molecules Stimulation of angiogenesis genes Mutation of cell cycle and DNA repair genes Loss of tumor suppressor genes Growth factor dysregulation
32
Activation of oncogenes
Ras proteins
33
Upregulation of proteases
MMPs Matrix metalloproteinases
34
Deactivation of adhesion molecules
E-cadherin
35
Stimulation of angiogenesis genes
VEGF Vascular endothelial growth factor (VEGF)
36
Mutation of cell cycle and DNA repair genes
p53, BRCA1, Cyclins
37
Loss of tumor suppressor genes
pRb APC
38
Growth factor dysregulation
EGF Epidermal growth factor ( HER2/neu
39
Factors Considered in Cancer Severity
Tumor size Histology Regional lymph Node involvement Presence of metastasis
40
higher stages are indicative of significant spreading and severe systemic disease
Disease severity
41
proliferation and metastasis occur at the expense of normal organ processes  cause of morbidity and mortality
Disease Progression
42
Localized primary tumor
stage I
43
Invasion of primary tumor through epithelium and into blood vessels
stage II
44
Migration of tumor into regional lymph nodes
Stage III
45
Metastasis and invasion of tumor to distant tissues
stage IIII
46
Produced either directly by the tumor or as an effect of the tumor on healthy tissue (host)
Tumor Markers
47
Tumor markers used to
Differentiate a tumor from normal tissue Detect the presence of a tumor based on measurements in the blood or secretions
48
such as ___ and ___, which are normally expressed during fetal development but do not occur normally in the tissues or sera of children and adults
oncofetal antigens - AFP and CEA
49
proteins occurring in epithelial cellls that become elevated in tissue and serum in adeno- and squamous cell carcinomas, such as the ____, ___ and ___
CA 19-9, CA 125, and CA 15-3 proteins
50
β chain of human chorionic gonadotropin (β-hCG),
polypeptide hormones,
51
such as the placental isoform of alkaline phosphatase, that become elevated in the serum of patients with specific tumors
specific enzymes
52
None of the tumor markers discovered had sufficient specificity and sensitivity in the general population It is not recommended for most tumor markers, especially in an asymptomatic population
Screening
53
The screening of primary hepatoma in Asian countries is based on the measurement of ___
Alpha-Fetoprotein (AFP) serum AFP
54
First tumor marker recommended for screening for prostate cancer in men older than age of 50. The purpose was to detect prostate cancer at early curable stages, when the tumor is still confined inside the organ.
Prostate-Specific Antigen (PSA) and Free PSA
55
Two major forms of Prostate-Specific Antigen (PSA) and Free PSA
Free PSA and a PSA –alpha1- antichymotrypsin (PSA-ACT) Free PSA percentage of free PSA to PSA-ACT
56
Free PSA and a PSA –alpha1- antichymotrypsin (PSA-ACT) Free PSA percentage of free PSA to PSA-ACT ratio may help differentiate _____ from __
benign prostate hyperplasia (BPH) from prostate cancer.
57
Several familial cancers are associated with germline mutations in various genes. The most prominent are genes for susceptibility to ___ and ___ such as ___ and __ are now available to screen these families for the identification of carriers.
Susceptibility Genes breast and ovarian cancer, such as BRCA1 and BRCA2
58
One of the two most useful applications of tumor markers involves their use in monitoring the course during treatment of the cancer patient. The measurement of serum tumor markers during treatment gives an indication of the effectiveness of the antitumor drug used and provides a guide for the selection of the most effective drug for each individual case.
Monitoring Treatment
59
Monitoring tumor markers for the detection of the recurrence following the surgical removal of the tumor. It is desirable to monitor the patient using a ___ test to detect recurrence as early as possible. It should be noted that the appearance of the most circulating tumor markers have a lead time of several months __ prior to the stage at which many of the physical procedures can be used for the detection of the cancer.
Detection of Recurrence - highly sensitive tumor marke - (3-6 months)
60
Determination is based on the assessment of tumor ____, which, in turn, determines how a patient should be treated. - factors measured in the clinical laboratory also indicate risk and predict the length of a relapse-free, as well as overall, survival period at the time of the primary therapy. High levels of serum tumor marker measured during diagnosis would indicate the presence of a ___ associated with a poor prognosis.
Prognosis -aggressiveness - malignant or metastatic tumor
61
Detecting the phenotypes in the blood circulation corresponding to early mutations of a cancer allows the detection of early neoplasm at the curable stage. It should be noted that several risk factors may lead to ___, which can be identified and eliminated with diet adjustment and lifestyle change Measurement of all mutant phenotypes and risk factors in the circulation would help to identify individuals at risk for cancer or detect early tumors in benign state.
malignant or metastatic tumor -tumorigenesis
62
Previously, drugs used in chemotherapy were predominantly _____ that were considerably toxic and had limited efficacy.
Target Therapy - DNA-active drugs
63
Inhibition of tumor cell proliferation may also be effective by introducing agents (or genes) that turn off the signaling pathway or pathways that specifically drive proliferation within a given tumor or tumor type.
Target Therapy
64
The prevailing new rationale is aimed at the development of ____ on the basis of characterized mechanisms of action. The specific defect of the tumor identified by these new tumor markers should, therefore, lead to the design of more specific drugs, including antibodies and small molecules, which inhibit growth factor receptors tyrosine kinases.
Target Therapy - target-selective “smart” drugs
65
Most used method to measure tumor markers
Immunoassays
66
- determined by analyzing specimens spanning the reportable range
Linearity
67
___ - antigen excess > analyte concentrations exceed the analytical range excessively
Hook Effect
68
circulating antibodies against human or animal immunoglobulin reagents > HAMAs
Heterophile antibodies -
69
Used to detect endocrine metabolites Tumor markers – detect ____ Not subject to hook effect, lot-to-lot antibody variation and heterophile antibody
High Performance Liquid Chromatography - catecholamine metabolites
70
identified in tissue sections typically from a fine-needle aspirate or biopsy samples
Immunohistochemistry and Immunofluorescence
71
___ incubated with tissue sections - detect the presence (or absence) of antigens using colorimetric or fluorescent secondary antibodies
Immunohistochemistry and Immunofluorescence -Specific antibodies -
72
Enzyme Assays
PSA - prostate cancer immunoassay ALP alkaline phosphatase (ALP) LDH Lactate dehydrogenase (LDH)
73
Biopsy indication ___ and ___
Screening - AFP and PSA
74
high levels indicative of dse.
Diagnosis - Metanephrines - HVA/VMA Prolactin - PTH - Chromogranin A
75
high levels asso w/ poor prognosis receptor stat used for indication of chemotheraphy
Prognosis - Beta2 microglobulin - CA125 CEA - LD - Her-2/neu ER PR
76
Monitor efficacy of chemotheraphy: residual dse after surgery
Monitoring treatment -CA125 CEA CA19-9 AFP hCG - PSA -SPE
77
Inc asso with relapse
CA15-3 CA125 CEA AFP hCG PSA
78
Enzyme tumor markers
Prostate specific antigen Lactate dehydrogenase Alkaline phosphatase Neuron specific enolase
79
Tumor marker: Prostate specific antigen
Tumor type Prostate cancer Method Immunoassay Specimen serum Clinical utility Prostate cancer screening, therapy monitoring and recurrence.
80
TM: LDH
Tumor type Hematologic malignancies Method Enzyme assay Specimen serum Clinical utility Prognostic indicator, elevated nonspecifically in numerous cancer
81
TM: ALP
Tumor type metastatic carcinoma of bone, hepatocellular carcinoma, osteosarcoma, lymphoma, leukemia Method enzyme assay Specimen serum Clinical utility determination of liver yand bone involvement: nonspecific elevation in many bone- related and liver cancers
82
TM: Neuron- specific enolase
Tumor type Neuroendocrine tumors Method radio immunoasssay, immunohistochemistry Specimen serum Clinical utility prognostic indicator and monitoring dse progression for neuroendocrine tumors
83
Serum protein tumor markers
Serum M proteins serum free light chains b2 microglobulin
84
Serum M proteins
Tumor type plasma cell dyscrasias Method serum protein electrophoresis/immunofixation electrophoresis Specimen serum Clinical utility dx, therapeutic monitoring of plasma malignancies
85
serum free light chains
Tumor type plasma cell dyscrasias Method immunoassay Specimen serum Clinical utility dx, therapeutic monitoring of plasma malignancies
86
b2 microglobulin
Tumor type hematologic malignancies Method immunoassay Specimen serum Clinical utility prognostic marker for lymphoproliferative disorders
87
Endocrine tumor markers
ACTH adrenocorticotropic hormone ADH antidiuretic hormone C peptide calcitonin chromogranin a cortisol gastrin GH growth hormoe HVA homovalinic acid 5-HIAA hydroxyindoleacetic acid Metanephrines (fractionated) PTH PRL VMA
88
ACTH adrenocorticotropic hormone
Tumor type pituitary adenoma, ectopic ACTH-producing tumor Method immunoassay Specimen serum Clinical utility prognostic marker for lymphoproliferative disordersx of ectopic- ACTH-producing tumor
89
ADH antidiuretic hormone
Tumor type posterior pituitary tumors Method immunoassay Specimen serum Clinical utility DX of SIADH
90
C peptide
Tumor type insulin secreting tumors Method immunoassay, elisa Specimen serum Clinical utility DX of insulinoma
91
calcitonin
Tumor type MTC and neuroendocrine tumors Method immunoassay, Specimen serum Clinical utility screening response to therapy and monitoring recurrence of MTC
92
chromogranin a
Tumor type Pheochromocytoma, neuroblastoma, carcinoid tumor, cmall cell lung cancer Method elisa ria Specimen serum Clinical utility aids in dx of carcinoid tumors phepchromocytomas and neuroblastomas
93
cortisol
Tumor type adrenal tumors Method ia Specimen serum/ urine Clinical utility aids in dx of carcinoid tumors phepchromocytomas and neuroblastomas of cushing syndrome, adrenal adenoma
94
Gastrin
Tumor type neuroendocrine tumor Method ia Specimen serum Clinical utility zollinger ellison syndrome gastrinoma
95
GH
Tumor type pituitary adenoma, ectopic GH-secreting tumors Method ia Specimen serum Clinical utility dx and post monitoring of acromegaly
96
HVA homovalinic acid
Tumor neuroblastoma, pheochromocytoma, paraganglioma Method hplc Specimen 24hr urine Clinical utility dx of carcinoid tumors
97
5-HIAA hydroxyindoleacetic acid
Tumor typecarcinoid tumors Method hplc Specimen 24hr urine Clinical utility dx and screening of carcinoid tumors of pheochromocytoma
98
Metanephrines (fractionated)
Tumor type neuroblastoma, pheochromocytoma, paraganglioma Method hplc Specimen 24hr urine Clinical utility dx and screening of pheochromocytoma
99
PTH
Tumor type parathyroid adenoma Method ia Specimen serum Clinical utility dx and postsurgical monitoring of parathyroid adenoma
100
VMA
Tumor type neuroblastoma, pheochromocytoma, paraganglioma Method hplc Specimen 24hr urine Clinical utility dx and screening of pheochromocytomaF neuroblastoma
101
nonseminomatous tumors
Germ cell tumor - 1. yolk sac tumor(endodermal sinus tumor) AFP Increased hCG No 2. cholirocarcinoma AFP no hCG inc 3. embronal carcinoma AFP inc hCG +/- 4. teratoma AFP no hCG No
102
Seminoma
GCT NONE AFP Not elevated in pure tumors hCG +/-
103
CHO and Cancer Ag tumor markers
CA19-9 CA15-3 CA27-29 CA-125
104
CA19-9
Tumor type Gastrointestinal cancer and adenocarcinoma Method Immunoassay Specimen Serum Clinical utility Monitoring pancreatic cancer
105
CA15-3
Tumor type Metastatic breast cancer Method Immunoassay Specimen Serum Clinical utility Response to therapy and detecting recurrence
106
CA27-29
Tumor type Metastatic breast carcinoma Method Immunoassay Specimen Serum Clinical utility Response to therapy and detecting recurrence
107
CA-125
Tumor type ovarian cancer Method Immunoassay Specimen Serum Clinical utility monitoring therapy
108
Receptor tumor markers
Estrogen receptor progesterone receptor Her-2/neu Epidermal growth factor receptor
109
Estrogen receptor progesterone receptor
Tumor type breast cancer Method ihc Specimen biopsy Clinical utility hormonal therapy indicator
110
Her-2/neu
Tumor type breast cancer Method ihc, fish, elisa Specimen biopsy Clinical utility prognostic and hormonal therapy indicator
111
Epidermal growth factor receptor
Tumor type head, neck, ovarian, cervical cancer Method ihc Specimen biopsy Clinical utility prognostic indicator
112
Most well known angiogenic factors:
Vascular endothelial growth factor (VEGF) Acidic and basic fibroblast growth factor (aFGF and bFGF) Transforming growth factor alpha (TGF-alpha)
113
Most well known angiogenic factors:
Vascular endothelial growth factor (VEGF) Acidic and basic fibroblast growth factor (aFGF and bFGF) Transforming growth factor alpha (TGF-alpha)

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