Pakistan Society Of Chemical Pathologists
Distance Learning Programme In Chemical Pathology
(DLP-2)
Lesson No 19
Tumour Markers
By
Col Naveed Asif
Consultant Chemical Pathologist /
Section Head Endocrinology and Tumour Markers
Department of Chemical Pathology and Endocrinology
AFIP Rawalpindi
&
Brig Aamir Ijaz
MCPS, FCPS, FRCP (Edin), MCPS-HPE
HOD and Professor of Pathology /
AFIP Rawalpindi
Part I
MCQs (One Best Type)
Q.1: Tumor markers that are to be put to clinical use should have certain
characteristics that are applicable in all situations. An ideal marker has a
number of characteristics. All the following are characteristics of an Ideal
tumor marker EXCEPT:
a.
b.
c.
d.
e.
Have 100% accuracy in differentiating between healthy individuals and tumor
patients
Have a normal plasma level, urine level or both in the presence of micro
metastasis
Have high positive and negative predictive value
Precede and predict recurrences before they are clinically detectable
Provide a lead-time over clinical diagnosis
b. Have a normal plasma level, urine level or
both in the presence of micro metastasis
Tumor Marker
• Substances present in, or produced by a tumor itself or produced
by host in response to a tumor that can be used to differentiate a
tumor from normal tissue or to determine the presence of a
tumor based on measurements in blood or secretions
• Such substances are found in cells, tissues or body fluids
• Measured qualitatively or quantitatively by chemical,
immunological or molecular biological methods
• Some tumor markers represent re-expression of substances
produced normally by embryonically closely related tissue e.g.
CEA in Colon, stomach, liver, and pancreas
Q 2. Tumor markers are substances present in, or produced by, a tumor itself
or by host. It can be detected in plasma or other body fluids including urine by
different techniques. Which of the following markers is estimated in urine?
a.
b.
c.
d.
e.
Human kallikerin 2
Intercellular adhesion molecule-1
Lysophosphatidic acid
Nuclear matrix proteins
Urokinase-Plasminogen activator inhibitor
d. Nuclear matrix proteins
Human Kallikerin 2
• Human glandular kallikrein 2 (hK2) is a prostate-specific kallikrein
produced by the prostatic epithelium with approximately 80% DNA
sequence homology with PSA
• hK2 is a potent protease, with more than 20,000 times the activity of the
relatively weak protease PSA
• While PSA production is often decreased in poorly differentiated prostate
cancers, hK2 production appears to be increased
• In prostatism patients the ratio of hK2 to free PSA improves the
discrimination between Prostate Cancer and Benign Hyperplasia within the
diagnostic “Gray Zone” of total PSA 4 to 10 ng/ml
• Monoclonal antibodies have been produced to detect hK2
Intercellular Adhesion Molecule-1
• ICAM-1 (Intercellular Adhesion Molecule 1) also known as
CD54 (Cluster of Differentiation 54)
• A member of the immunoglobulin superfamily Ig-like cell
adhesion molecule expressed by several cell types including
leukocytes and endothelial cells
• Derangement of ICAM-1 expression contributes to the clinical
manifestations of a variety of diseases, predominantly by
interfering with normal immune function.
• Among these are malignancies (e.g., melanoma and
lymphomas), many inflammatory disorders (e.g., asthma and
autoimmune disorders), atherosclerosis, ischemia, certain
neurological disorders, and allogeneic organ transplantation.
Lysophosphatidic Acid
• LPA is a phospholipid derivative, identical in structure to
phosphatidic acid (PA)
• Bulk of LPA production occurs in bodily fluids, outside the
cell. From there, it can bind to, and activate, upwards of six
different cell surface receptors, initiating a diverse range of
signaling cascades resulting in cell proliferation
• Dysregulation of LPA receptors can lead to hyperproliferation,
which may contribute to oncogenesis and metastasis
• Alongwith CA 125, plasma LPA level can be a useful marker
for ovarian cancer, particularly in the early stages of disease
Nuclear Matrix Proteins
• The nuclear matrix (NM) is a structure resulting from
the aggregation of proteins and RNA in the nucleus of
cells
• Nuclear matrix proteins (NMPs) make up the internal
structure of nucleus. They are associated with key
reactions in nucleus like DNA replication and RNA
synthesis
• Expression pattern of NMP has become an important
early indicator for numerous cancers/tumors
• NMPs released by cancer cell are different from those
in normal cell
• Particular importance in bladder cancer patient, owing
its excretion in urine
Urokinase Plasminogen Activator System
• Urokinase plasminogen activator (uPA) is a serine protease
with an important role in cancer invasion and metastases .
• When bound to its receptor (uPAR), uPA converts plasminogen
into plasmin and mediates degradation of the extracellular
matrix during tumor cell invasion.
• High levels of uPA and uPAR, as well as the plasminogen
activator inhibitor -1 (PAI-1), have been associated with shorter
survival in women with breast cancer; in contrast, high levels
of PAI-2 appear to be associated with better outcomes .
Urokinase Plasminogen Activator System (cont)
• One explanation is that tumor may be overproducing uPA,
allowing cancer cells to spread beyond the tumor. High levels
of PAI-1 may not be able to inhibit the growth of the tumor
• uPA and PAI-1 can be measured by ELISAs on a minimum of
300 mg of fresh or frozen breast cancer tissue
• Both are used for the determination of prognosis in patients
with newly diagnosed, node-negative breast cancer
• Overexpression of uPA and/or PAI-1 have been consistently
related to poor prognosis
• If a patient has high levels of uPA and PAI-1, risk of recurrence
of disease is very high
Q. 3: Changes in concentration of tumor markers is used to
describe the true status of a tumor. Different criteria/definitions
have been devised based on various scientific facts. “A linear
increase in the concentration of tumor marker in three
consecutive samples on log scale provided no therapy is given”.
This statement truly describes:
a.
b.
c.
d.
e.
Confirmation of diagnosis
Partial remission of tumor
Recurrence of tumor
Relapse of tumor
Screening of tumour
c. Recurrence of tumor
Q.4: A 59 years male is a known patient of chronic liver disease. His recent
result of Alpha Fetoprotein (AFP) is 197ng/ml. Now the major challenge for a
Chemical Pathologist is to offer another biochemical test to rule out
hepatocellular carcinoma in this patient. Many new candidate tumour markers
have been suggested to be used alone or in combination with AFP.
Which of the following biomarkers has the strongest evidence to be used
in such patients?
a.
b.
c.
d.
e.
Alpha-L-fucosidase activity
Human carboxylesterase 1
Lens culinaris agglutinin-reactive AFP
Transforming growth factor-beta-1
Tumor-associated isoenzymes of gamma-glutamyl transpeptidase
c. Lens culinaris agglutinin-reactive AFP
Lens Culinaris Agglutinin-reactive AFP
(AFP-L3)
• Lens culinaris agglutinin-reactive AFP (AFP-L3) is a fucosylated
fraction of AFP that may be a helpful diagnostic and prognostic
maker of hepatocellular carcinoma (HCC), particularly in
patients with low serum AFP levels.
• The sensitivity and specificity of AFP-L3 assay (using a cut-off
of ≥5 percent) for HCC were found to be 42 and 85 percent,
respectively.
• In addition, patients with high AFP-L3 levels using the highly
sensitive assay had lower survival rates than patients with AFPL3 levels of less than 5 percent.
Alpha-L-Fucosidase Activity
• The lysosomal hydrolase, alpha-L-fucosidase (alpha-L- fucoside
fucohydrolase; (AFU), is present in many mammalian tissues including
humans where it degrades fucose-containing glycoconjugates.
• Deficiency of AFU results in a rare neurovisceral storage disease
known as fucosidosis
• Women with low serum activity of the enzyme may be prone to ovarian
carcinoma.
• Raised serum concentrations of AFU have been described in patients
with a variety of benign diseases, including diabetes, hyperthyroidism
and cirrhosis, alcoholic hepatitis and acute viral hepatitis.
• Increased AFU activity has been found in patients with carcinoma of
the lung, breast, stomach, ovary, uterus and hepatocellular carcinoma
• AFU is both less sensitive and less specific than alpha-fetoprotein as a
serum marker of hepatocellular carcinoma.
Human Carboxylesterase 1
• Liver carboxylesterase 1 (CES1, hCE-1 or CES1A1) is an enzyme, also
historically known as serine esterase 1 (SES1), monocyte esterase and
cholesterol ester hydrolase (CEH)
• It is involved in both drug metabolism and activation, as well as other
biological processes including
 Detoxification of xenobiotics
 Involvement in cholesterol metabolism
 Catalyses the hydrolysis of heroin and cocaine
 Activation of many prodrugs such as angiotensin-converting enzyme
(ACE) inhibitors,
Carboxylesterase 1 deficiency may be associated with non-Hodgkin
lymphoma or B-cell lymphocytic leukemia
Transforming Growth Factor-beta-1
• Transforming growth factor beta 1 or TGF-β1 is a polypeptide
member of the transforming growth factor beta superfamily of
cytokines
• It is a secreted protein that performs many cellular functions,
including the control of cell growth, cell proliferation, cell
differentiation and apoptosis
• Heterozygous mutations in TGFB1 gene result in a rareCamurati-Engelmann disease type I (CED) with characteristic
anomalies in the skeleton. It is a form of dysplasia
• Some TGFB1 gene mutations are acquired. The TGFβ-1
overexpression occurs in certain types of prostate cancers,
breast, colon, lung, and bladder cancers
Tumor-associated Isoenzymes Of Gamma-glutamyl
Transpeptidase
• γ-glutamyl transpeptidase is a membrane-bound enzyme which
hydrolyzes γ-glutamyl
• y-GT activity is high in foetal liver, in hepatocellular
carcinoma (HCC) and in the preneoplastic lesions which
precede these tumours, but is low in adult liver tissue
• In damaged hepatocytes, particularly in hepatocarcinogenesis,
GGT is significantly released into the blood from hepatic
tissues
• However the total activity of GGT has a significant overlap
with various liver diseases which limits its value in diagnosis
• However sensitivity and specificity of GGT is increased in
HCC when combined with AFP
Q: 5. A 35 years old lady presented with five years history of
pelvic mass. On laparotomy it turned out to be of ovarian origin.
Histopathology revealed carcinoma ovary. Blood sample was sent
for CA 125 level and result was 20 IU/ml. What could be the
most likely cause of normal CA 125 level?
a.
b.
c.
d.
e.
Endometrial carcinoma alongwith carcinoma ovary
Haemolysed sample
Mucinous type of carcinoma ovary
Multi-loculated cysts in ovaries
Photometric method of analysis
c. Mucinous type of carcinoma ovary
CA 125
• Cancer Antigen (CA) 125 is a high molecular weight
glycoprotein expressed by epithelial ovarian tumors and other
pathologic and normal tissues of mullerian duct origin
• CA 125 is a most promising marker for ovarian cancer
• About 80% of non-mucinous epithelial ovarian cancers have
raised CA 125 levels, while normal levels are seen in 75% of
mucinous tumors like Brenner, sex cord and germ cell tumors
• CA 125 is used for monitoring response to therapy, for
detecting residual disease following initial therapy and for
detection of recurrent metastasis in ovarian cancer.
• However it has limitations in early detection of ovarian cancer
due to its low sensitivity and low specificity
Benign conditions with
raised CA 125 levels
NON -GYNECOLOGICAL
Liver failure
Chronic active hepatitis
Cirrhosis with ascites
Acute and chronic
pancreatitis
Peritonitis
Pleuritis
Pericarditis
Peritoneal dialysis
Pneumonia
Peritoneal sarcoidosis
Meig’s syndrome
GYNECOLOGICAL
Menstruation
Early pregnancy
Endometriosis
Pelvic inflammatory disease
Uterine fibroids
Adenomyosis
Ovarian cyst
Abruptio placenta
Salpingitis
Hydatiform mole
Malignant conditions with
raised CA 125levels
Epithelial ovarian cancer
Endometrial cancer
Endocervical cancer
Fallopian tube cancer
Gastrointestinal malignancy
Breast cancer
Liver cancer
Lung cancer
Carcinoma of kidney
Lymphoma
Malignant mesotheliomas
Immature teratoma
Q. 6: Hyperglycosylated hCG (hCG-H) is a glycoprotein with the
same polypeptide structure as hCG with higher molecular weight
and much larger N- and O-linked oligosaccharides. It has some
important clinical applications. hCG–H is useful in all these
conditions EXCEPT:
a.
b.
c.
d.
e.
Detecting non-seminomatous testicular tumors
Monitoring placental implantation in pregnancy
Predicting down syndrome pregnancies
Predicting eclampsia during pregnancy
Predicting pregnancy outcome after in-vitro fertilization
a. Detecting non-seminomatous testicular tumors
Hyperglycosylated hCG (hCG-H)
• Hyperglycosylated hCG (hCG-H) is a major glycosylation
variant of hCG which has a different 3dimensional structure, is
also produced by placenta
• It is made by extravillous cytotrophoblast cells of placenta
• It promotes trophoblast invasion during choriocarcinoma,
growth of cytotrophoblast cells and placental implantation in
pregnancy
• hCG-H is the principal form of total hCG made in early
pregnancy. In serum it accounts for 90 +/- 11% of total hCG in
the 3rd complete week of gestation and 54 +/- 7% of total hCG
during the 4th complete week of gestation. Its level decreases
in remaining pregnancy
Clinical Applications of HCG-H
• Gestational trophoblastic diseases are governed and regulated
by the presence of hCG-H
• Management of quiescent gestational trophoblastic diseases
• Predicting down syndrome pregnancies- Triple test (hCG/hCGH, a-fetoprotein, unconjugated estriol, inhibin)
• Predicting hypertensive disorders
• To differentiate pregnancies that will miscarry and pregnancies
that will go to term
• To test for early pregnancy in in-vitro fertilized and infertility
clinic cases
Q. 7: A new tumour marker is being evaluated in a Chemical Pathology lab for
the diagnosis of a tumour. At a serum cut off level of 2.5 ng/ml, the sensitivity
and specificity of the tumour marker is 94% and 56%, respectively. Increasing
the level to 8.0 ng/ml the sensitivity and specificity become 51% and 93%,
respectively. The Chemical Pathologist is in search of a cut-off value with
optimum sensitivity and specificity. The most appropriate statistical procedure
for this purpose would be:
a.
b.
c.
d.
e.
Chi-square test
Kaplan–Meier survival estimator
Pearson` correlation coefficient
Receiver operating curve
Student`s t test
d. Receiver operating curve
Q. 8. A 62 year man has Serum PSA level of 6.9 ng/ml.
According to the available evidence, the most promising
method of PSA testing to avoid unnecessary prostatic
biopsy in this patient is:
a.
b.
c.
d.
e.
Free to total PSA percentage
PSA assay with age related cut-off values
PSA Density
PSA velocity
Serum isoform [-2]proPSA
e. Serum isoform [-2]proPSA
Improving the Accuracy of PSA
• Numerous strategies have been proposed to
improve the diagnostic performance of PSA
when levels are less than 10.0 ng/ml
• These strategies include
 Measuring PSA velocity
 PSA density
 Free PSA
 Complexed PSA
 Using age- and race-specific reference ranges
 Serum isoform [-2]proPSA
Free to total PSA percentage
• The ratio of free-to-total PSA is reduced in
men with prostate cancer
• Biopsies should be performed only in men
with lower ratios.
• An optimal cutoff selected for biposy is 25 %
• Men with a normal free-to-total PSA ratio still
had an 8% probability of having cancer
PSA density:
PSA concentration / prostatic volume
•It is determined by trans-rectal
ultrasonography
• PSA density measurements better
discriminates between cancer and noncancer groups than PSA levels alone
PSA velocity
• It is the rate of PSA increase as a function of
time
• A baseline concentration of PSA in each
patient is established, the rate of increase of
PSA is then calculated
• Men with a PSA velocity > 0.75 ng/ml/year
are at increased risk of being diagnosed with
prostate cancer
PSA assay with age related
cut-off values
AGE (in years)
CUTOFF
40 to 49
0 to 2.5 ng/ml
50 to 59
0 to 3.5 ng/ml
60 to 69
0 to 4.5ng/ml
70 to 79
0 to 6.5 ng/ml
Serum isoform [-2]proPSA
• It is also known as P2PSA
• Is a specific isoform of the PSA proenzyme
proPSA
• Increases the detection of prostate cancer for
men with PSA values between 2.0 to 10.0 ng/ml
• Reduces the number of unnecessary biopsies by
7.6 % with sensitivity of 95 % for detecting
prostate cancer
Q. 9: In the last a few decades cancer research has resulted in
discovery of many new tumour markers e.g. Osteopontin and
human epididymis protein 4 (HE4). Which of the following
laboratory techniques is most helpful in the discovery of these
tumour markers through their genetic over-expression :
a.
b.
c.
d.
e.
Chemiluminescence
DNA sequencing
Mass spectrometry
Microarray
PCR
d.Microarray
Q. 10: A 32 y male has a unilateral swelling of his left testis and symptoms of
hyperthyroidism. His thyroid profile was as following:
•
Serum Free T3
4.12 ng/ml
(1.60-4.20)
•
Serum T4
2.18 pg/ml
(0.70-1.68)
•
Serum TSH
0.14 mIU/L (0.30-4.0)
His physician has sought your advice regarding the diagnosis of testicular
swelling in this patient. The most probable testicular tumour you would like to
exclude is:
a.
b.
c.
d.
e.
Embryonal carcinoma
Granulosa cell tumour
Leydig cell tumour
Sertoli cell tumour
Unclassified tumour
a. Embryonal carcinoma
Hyperthyroidism Associated with Testicular Tumor
• Germ cell tumors are divided into seminomatous or
non-seminomatous types
• Ninety percent of non-seminomatous tumors express
either alphafetoprotein or hCG
• Intact hCG consists of two subunits. The α subunit is
identical to the α subunit of the pituitary
gonadotrophins and thyroid-stimulating hormone
(TSH). Β subunit is unique to hCG
• hCG can activate the TSH receptor when present in
excess and induce thyrotoxicosis.
Part II
Short Answer Questions:
Q.11: A 32
years old lady presented in surgical OPD with lump in her left breast
for last six months. On examination there was thickness, swelling and redness
of skin with nipple retraction and bloody discharge. Later on her mastectomy
was done and specimen was sent for histopathology. Her laboratory tests
revealed following results:
• CEA
: 52 ng/ml (< 2.5)
• CA 15-3
: 86 U/ml (30)
• Estrogen receptor (ER)
: Negative in breast tissue by IHC*
• Progesterone receptor (PR) : Negative in breast tissue by IHC
• HER2/neu
: Negative in breast tissue by IHC
Please answer following questions
a. What is name of breast cancer she is suffering from?
b. Can ER, PR and HER2/neu be assayed in serum? If yes, please write
name(s) of assay which can be used for analyses in serum.
Q.11:
a. What is name of breast cancer she is suffering from?
Triple-negative breast cancer
b. Can ER, PR and HER2/neu be assayed in serum? If yes,
please write name(s) of assay which can be used for
analyses in serum.
• No serum assay is available for ER and PR.
• Only Her2/neu can be assayed in serum by following
technique
• Enzyme immunoassay
• Chemiluminescent assay
•
•
A 40 years old female has five years history of iron deficiency anaemia
and constipation off and on for same duration. She never consulted doctor
for these complaints. Later on she developed severe pain in right iliac fossa
and was operated upon for Acute Appendicitis. During closing of abdomen
surgeon found abnormal small nodular growth on omentum. On further
exploration likewise growth was found in both ovaries. Tissue was taken and
sent for histopathology. IHC was done on tumor tissue which revealed CK7
negative and CK20 positive in tumor cells. Other laboratory tests were also
advised. Their results revealed:
Q.12:
• CEA:
• CA 19.9:
• CA 242:
25 U/l
111 U/ml
55 U/ml
(less than 2.5)
(less than 37)
(less than 20)
• Stool for occult blood is equivocal
a.
b.
Please answer following questions
What type of cancer she is having?
Name a single tumor marker emerging as a reliable screening test for this
tumor. What is the most suitable sample for its detection? Comment in not
more than one line about its sensitivity and specificity in this cancer.
Q.12:
a. What type of cancer she is having?
Colorectal adenocarcinoma with ovarian metastasis
b. Name a single tumor marker emerging as a reliable screening test
for this tumor. What is the most suitable sample for its detection?
Comment in not more than one line about its sensitivity and specificity
in this cancer.
(1) Increased stool (fecal) levels of Tumor M2-Pyruvate Kinase (TM2-PK) an
excellent method of screening for colorectal tumors.
Sample required for its detection is stool.
It is a tumor marker with high sensitivity and high specificity with no false
negative, but false positive may be occurring. When measured in feces with a
cutoff value of 4 U/ml, its sensitivity has been estimated to be 85% for colon
cancer and 56% for rectal cancer. Its specificity is 95%.
(2) Fecal DNA testing for which stool sample (collection of one entire bowel
movement) is required. Its sensitivity for detection of adenocarcinoma is 7277% and Specificity is 95.2%.
Q.13: A 39
years old lady reported to a private Gynae clinic
with full term pregnancy. She gave birth to a baby boy
through normal vaginal, but obstructed delivery. After about
one month same lady ended up in the emergency in critical
condition with abdominal pain, vaginal bleeding, cough,
difficulty in breathing and fits.
Please answer following questions
a. What is most likely diagnosis?
b. Name TWO biochemical tests which can be helpful to
confirm the diagnosis. Write in not more than TWO lines
importance and interpretation of the test
Q.13:
a. What is most likely diagnosis?
Choriocarcinoma or gestational trophoblastic neoplasm
b. Name TWO biochemical tests which can be helpful to confirm the
diagnosis. Write in not more than TWO lines importance and
interpretation of the test
1. Serum β-hCG level – it becomes normal within 2-4 weeks after a
normal delivery. So persistent elevation after a nonmolar pregnancy is
indicative of GTD.
2. Serum Hyperglycosylated hCG (hCG-H)- it is a very sensitive
marker to differentiate active from quiescent GTD. If hCG-H is >40%
of total hCG or > 3000 IU/L, it is indicative of active GTD and
interventions such as hysterectomy or chemotherapy should be done
3. CSF (cerebrospinal fluid) to serum hGC ratio: Normal CSF
(cerebrospinal fluid) to serum hGC ratio is 1:60, levels greater than
1:60 indicate cerebral metastases
Q.14: Currently
a number of tumor markers are available for
ovarian cancer. CA125 is the only marker that can be
recommended for use. New ovarian cancer markers offer
promise, however, their contribution to the current standard
of care is unknown and further clinical trials are needed. CA
125 lacks sensitivity and specificity particularly in early
diagnosis of ovarian cancer. Many strategies have been
proposed to improve the diagnostic accuracy of CA 125 for
ovarian cancer, though there is no consensus about
acceptance of these modifications.
Please answer following questions (One mark each):
a. Name FOUR strategies proposed for improvement of
diagnostic performance of CA 125.
b. Write brief description of THREE of these strategies (not
more than 3-4 lines for each).
Q.14: a.
Name FOUR strategies proposed for improvement
of diagnostic performance of CA 125.
1. Risk of malignancy index (RMI)
2. Risk of ovarian malignancy algorithm. (ROMA)
3. OVA1 test
4. OVASure test
b. Write brief description of THREE of these strategies
(Please see next a few slides).
Risk of malignancy index (RMI)
• RMI combines three pre-surgical features: serum CA125 (CA125),
menopausal status (M) and ultrasound score (U). The RMI is a product of
the ultrasound scan score, the menopausal status and the serum CA125 level
(IU/ml).
• RMI = U x M x CA125
• The ultrasound result is scored 1 point for each of the following
characteristics: multilocular cysts, solid areas, metastases, ascites and
bilateral lesions. U = 0 (for an ultrasound score of 0), U = 1 (for an
ultrasound score of 1), U = 3 (for an ultrasound score of 2–5).
• The menopausal status is scored as 1 = pre-menopausal and 3 = postmenopausal
• The classification of 'post-menopausal' is a woman who has had no period
for more than 1 year or a woman over 50 who has had a hysterectomy.
• Serum CA125 is measured in IU/ml and can vary between 0 and hundreds
or even thousands of units.
Risk of ovarian malignancy algorithm.
(ROMA)
• Risk of ovarian malignancy algorithm is a qualitative serum test that
combines results of HE4, CA 125 and menopausal status into a
numerical score
• ROMA is intended to aid in assessing whether a premenopausal or
postmenopausal woman who presents with an ovarian adnexal mass
is at high or low likelihood of finding malignancy on surgery. ROMA
must be interpreted in conjunction with an independent clinical and
radiological assessment. The test is not intended as a screening or
stand-alone diagnostic assay.
• ROMA (HE4 + CA125) should not be used without an independent
clinical/radiological evaluation
• ROMA is determined using the following equation:
•
ROMA (%) = exp (PI)/[1 – exp(PI)]*100.
• 13.1% and 27.7% as the cutoff points for pre- and postmenopausal
patients, respectively, and predictive index =(PI)
OVA1 Test
• OVA1 test is a qualitative serum test that combines
the
result of five immunoassays into a single numeric
score.
Five markers are; CA 125, Prealbumin
(transthyretin),
apolipoprotein A1, transferrin and
beta 2 microglobulin
• Its a proprietary algorithm (i.e., OvaCalc) to determine the
likelihood of malignancy in women with pelvic mass for whom
surgery is planned
• It is indicated for women who meet the following criteria i.e.
age over 18, ovarian adnexal mass present for which surgery is
planned, and not yet referred to an oncologist.
• OVA1 score has values between 0 and 10.
Q.15: Cancer
is caused by the accumulation of genetic and
epigenetic mutations that normally play a role in the
regulation of cell proliferation, thus leading to uncontrolled
cell growth. Depending on how they affect each process,
these genes can be grouped into two general
categories: tumor suppressor genes (growth inhibitory)
and proto-oncogenes (growth promoting). Mutant alleles of
proto-oncogenes are called oncogenes.
Below is a list of different body tumors. You are required
to write ONE oncogene and ONE tumor suppressor gene
associated with each tumor:
a.
Colorectal cancer:
b.
Renal cancer
c.
Medullary thyroid carcinoma
d.
Lung cancer:
Q.15: a.
Colorectal cancer:
a.
K- ras mutation
b.
APC mutation
• The protein product of the normal KRAS gene is a GTPase and is an
early player in many signal transduction pathways necessary for the
propagation of growth
• Adenomatous polyposis coli (APC) also known as deleted in
polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the
APC gene.
• The APC protein is a negative regulator that controls Beta-catenin
concentrations and interacts with E-cadherin, which are involved in
normal cell adhesion
Q.15: b.
Renal cancer
a.
VHL mutation
b.
WTI mutation
• The VHL gene provides instructions for making a protein that
functions as part of a complex (a group of proteins that work
together) called the VCB-CUL2 complex. One of the targets of the
VCB-CUL2 complex is a protein called hypoxia-inducible factor 2alpha (HIF-2α). HIF-2α is one part (subunit) of a larger protein
complex called HIF. HIF controls several genes involved in cell
division, the formation of new blood vessels, and the production of
red blood cells. It is the major regulator of a hormone called
erythropoietin, which controls red blood cell production.
• The WTI gene encodes a transcription factor that contains four zinc
finger motifs at the C-terminus and a proline / glutamine-rich DNAbinding domain at the N-terminus. It has an essential role in the
normal development of the urogenital system
Q.15: c. Medullary
thyroid carcinoma
a. RET mutation
b. Sprouty 1
• RET is an abbreviation for "rearranged during
transfection." The RET proto-oncogene encodes a
receptor tyrosine kinase for members of the glial cell linederived neurotrophic factor (GDNF) family of
extracellular signalling molecules.
• Sprouty 1 (SPRY1) functions as a regulator of
fundamental signaling pathways. It is a key regulator of
proper organ and tissue development.
Q.15: d. Lung
cancer:
a. MAX mutation
b. LHX6 LIM homeobox 6 mutation
• Protein max also known as myc-associated factor X is a
protein
• that in humans is encoded by the MAX gene. yc is an
oncoprotein implicated in cell proliferation,
differentiation and apoptosis.
• LIM/homeobox protein Lhx6 is a protein that in humans
is encoded by the LHX6 gene. This gene encodes a
member of a large protein family that contains the LIM
domain, a unique cysteine-rich zinc-binding domain. The
encoded protein may function as a transcriptional
regulator and
Thank You and Best Of Luck