BreastBreastTumor markersTumor markers TopologyTopology

Mostafa Askar Askar

NCRRT ,Cairo, Egypt

What are Tumor What are Tumor MarkersMarkers？？

Biological substances synthesized and released by cancer cells or produced by the host in response to the presence of tumor

Detected in a solid tumor, in circulating tumor cells in peripheral blood, in lymph nodes, in bone marrow, or in other body fluid (urine, stool, ascites)

Potential Uses of Potential Uses of Tumor MarkersTumor Markers

Population Screening Diagnosis Establishing prognosis, staging Postoperatory evaluation Monitor treatment response Surveillance for recurrence Targets for therapeutic intervention

How to identify tumor How to identify tumor marker ? marker ?

On cell– Cytochemistry, Flow cytometry

On tissue– Histochemistry, Cytosol assays

In body fluids– Blood, urine, CSF, Amniotic fluid

Tumor markers are:Tumor markers are: Enzymes –PSA - prostate specific antigen , TK

(thymidine kinase) Hormones - GH, prolactin Imunoglobulines – IgG, IgM, IgA, IgD, IgE, 2-

microglobulin Glycoproteines, glycolipides

CA 125 (glykoprotein), CA 50 (glykolipid)

– Highly specific i.e. not detectable in benign disease and healthy subjects

– Highly sensitive i.e. detectable when only a few cancer cells are present

– specific to a particular organ

Ideal Tumour Marker should be….Ideal Tumour Marker should be….

– Correlate with the tumour stage or tumour mass

– correlate with the prognosis

– have a reliable prediction value

– but ideal tumour marker doesn´t exists

Ideal Tumour Marker should ….Ideal Tumour Marker should ….

True positives

True positives + False positives

Positive Predictive Value Positive Predictive Value of a Tumour Markerof a Tumour Marker

The probability with which a tumour exists within a control group in the case of positive test results

True negatives

True negatives + False negatives

Negative Predictive Value Negative Predictive Value of a Tumour Markerof a Tumour Marker

The probability with which no tumour exists within a control group in the case of negative test results

True negatives

True negatives + False positives

SpecificitySpecificityThe percentage of normal persons for whom anegative result is obtained. The greater the specificity, the fewer the false positives.

True positives

True positives + False negatives

Sensitivity Sensitivity The percentage of test results which are correctly positive in the presence of a tumour. The greater the sensitivity, the fewer the false-negatives.

– The concentration of a tumour marker which differentiates healthy subjects from diseased subjects

– usually taken as the mean concentration of a control group plus 2 standard deviations

– target specificity should be 95% ( 5% false positives)

Cut-off value

Healthy

0.0 100 ng/mL10.0

100% specificity (no false positives)….

Cut-off value (C15-3)

Healthy

0.0 100 ng/mL

Breast cancer

10.0100% specificity

But only 70% sensitivity (30% false negatives)!

Cut-off value (C15-3)

0.0 100 ng/mL

Breast cancer

2.0

100% sensitivity…..(no false negatives)

Cut-off value (C15-3)

Healthy

0.0 100 ng/mL

Breast cancer

2.0

But only 70% specificity!(30% false positives)

Cut-off value (C15-3)

Healthy

0.0 100 ng/mL

Breast cancer

At 4.0 ng/mL, 95% specificity and 95% sensitivity

4.0

Cut-off value (C15-3)

CA 15-3 can be used to monitor breast cancer patients.• Elevated blood levels are found in <10% of patients with early disease and in about 70% of patients with advanced disease.• CA 15-3 levels usually drop following effective treatment.• But CA 15-3 can also be elevated in other cancers such as benign breast conditions & hepatitis.

CA 15-3

So…

– CA15-3 is not sensitive or specific for screening, pre-op diagnosis or prognosis of breast cancer

– it has clinical utility in following the clinical course of breast cancer, detecting metastases and monitoring response to therapy

– rising CA15-3 levels indicate disease recurrence

CCAA 15-3 15-3

CA 27-29 is another marker that can be used to follow patients with breast cancer during or after treatment. CA 15-3 is the same markers as CA 15-3 but in a different way. This marker can be elevated in other cancers such as colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver.

CA 27-29

HER2 (or HER2/neu, erbB-2, or EGFR2)

HER2 :positive breast cancer in 25% of patients when overexpressed. with aggressive disease, poor clinical outcomes and shortened overall survival. Samples of tumour tissue (not blood sample) are used to test for HER2 status. Elevated in other cancers as stomach.

Hormone receptors 2 hormones often fuel the growth of breast cancer Cells (estrogen and progesterone receptors). About 2 out of 3 breast cancers test positive for at least one of these markers. Hormone receptor-positive breast cancers tend to grow more slowly. Cancers that have these receptors can be treated with hormone therapy such as tamoxifen or aromatase inhibitors. Samples of tumour tissue (not blood sample) are used to test for HER2 status.

Lipid-associated sialic acid in Lipid-associated sialic acid in plasma (LASA-P)plasma (LASA-P)

Is found elevated in various malignant diseases, such as in the breast, GI, or lungs.

It is also altered in leukemia, lymphoma, Hodgkin’s disease, and melanoma, as well as in nonmalignant inflammatory diseases.

Because it’s important to find cancer early and be able to follow it during or after treatment, researchers are looking for new and better tumor markers. But as doctors have learned more about cancer, they’ve found that the level of a single protein or other substance in the blood may not be the best marker for the disease. They are looking for better ways to find and follow the course of different cancers.

What’s new in tumor marker research?

• The study of patterns of DNA changes (or mutations) in cancer conditions. • mRNA, smRNA

Genomics

This technology looks at the patterns of all the proteins in the blood instead of looking at individual protein levels. New testing equipment allows doctors to look at thousands of proteins at one time.

Proteomics

Due to validated of patterns of all the proteins in concerned pathway

NFkb as example to explain

proteomics tools in signal Pathways

and other tools

QUESTIONS ???QUESTIONS ???

Edited By

Mostafa Askar2013

Mostafa_asker2@yahoo.com