Tumor markers are substances that can be measured by biochemical or immunochemical methods in tissues or body fluids to detect cancer and possibly a body, to determine the tumor burden prior to treatment and to monitor response to treatment (Morton K Schwartz 1993 ).
The first modern tumor marker used to detect cancer was HCH (human chorionic gonadotropin). A high level of HCG in the blood can be a sign of cancer of the placenta called gestational trophoblastic disease. Some ovarian and testicular cancers produce high quantity HCG as reproductive germ cells come from.
Hope in the research of tumor markers was that all cancers could once again be detected by a simple blood test. The first success came in 1965 when ACE (carcinoembryonic antigen) has been found in the blood of patients with colonic cancer. Until the late 1970’s there have been developed several other tests for different cancers: colorectal and pancreatic cancer CA19-9, CA15-3 for breast cancer, CA 125 for ovarian cancer.
None of these markers that do not meet the original aim to detect cancer in an early stage:
– Small amount of marker in the patient’s blood especially in early stadium
– Their serum level increases with tumor volume,
– Some cancer patients shows no serum tumor markers never
– May be nonspecific, meaning to be present in other benign conditions
These are the reasons why tumor markers are used to diagnose cancer but cancer patients diagnosed tracking to detect disease recurrence (Morton K Schwartz 1993).
Some terms are essential for understanding the clinical utility of tumor markers. Analytical sensitivity is the smallest amount of tumor marker that can be detected, and epidemiological measure is the ability to detect cancer.
Analytic specificity means the degree of interference by foreign substances that may be present in the sample, and epidemiological test is the ability in evaluating and identifying a population without cancer. In assessing tumor markers it must be known cancer prevalence in a given population and analytical precision test (Morton K Schwartz 1993).
The only marker in screening is widely used PSA (prostate specific antigen) screening used widely in 1990 because it has some advantages:
– It is produced only by the prostate, so a rise in PSA indicate a prostate problem
– PSA rises even in early cancers, so most prostate cancers are detected early and can be curable stadium
– The test is not perfect: -and other non-malignant diseases of the prostate can grow PSA
– Some men with prostate cancer have normal PSA levels
– High level of PSA others comes from a prostate cancer that would otherwise never have required treatment
Tumor markers are substances that can be measured by biochemical or immunochemical methods in tissues or body fluids to detect cancer and possibly a body, to determine the tumor burden prior to treatment and to monitor response to treatment.
In 1847 Sir Henry Bence Jones described in a patient’s urine what is referred to today as Bence Jones protein. (Morton K Schwartz, 1993).
In 1867, Sir Michel Foster reported amylase in blood and urinary amylase was initially proposed as a marker for pancreatic cancer.
In 1930 acid phosphatase was used in evaluating men with prostate cancer, and serum alkaline phosphatase won a widely accepted diagnosis of osteogenic sarcoma and other bone cancers.
Chorionic gonadotropin test urine has become a standard in the evaluation and monitoring choriocarcinoma.
The introduction of carcinoembryonic antigen (CEA) in 1965 and reporting elevated sensitivity and specificity of colon cancer resulted in a number of tumor associated antigens always increased which were proposed as useful in cancer diagnosis and treatment (Morton K Schwartz 1993).
Some terms are essential for understanding the clinical utility of tumor markers. Analytical sensitivity is the smallest amount of tumor marker that can be detected, and epidemiological measure is the ability to detect cancer. Analytic specificity in the evaluation means the degree of interference with foreign substances can be present in the sample, and epidemiologically is the ability of the test to identify cancer-free population. In assessing tumor markers cancer prevalence in a given population needs to be known by precision analytical test (Morton K Schwartz 1993).
Positive predictive value of the test is the number of real tests positive tests divided by the sum of positive and tests false-positive real.
Negative predictive value is the number of false negative tests divided by the sum of false negative tests and negative real (Morton K Schwartz 1993).
Carcino-embryonic antigen (CEA)
ACE is a cell surface glycoprotein of MW 200 of kd.
In 1969 it was reported that ACE plasma was increased in 35 of 36 patients with colon adenocarcinoma (Schwartz MK 1967)
ACE increases are seen in more than 30% of patients with lung cancer, liver, pancreas, breast, colon, ENT, bladder, cervix and prostate (MK Schwartz 1967).
The antigen may be found in normal tissues and elevated plasma levels correlate with stage and extent of disease, the degree of tumor differentiation and metastasis headquarters (MK Schwartz 1967).
From 1425 normal nonsmoker people, 98.7% had values below 5 ng / ml. In 857 patients with a history of smoking increases normal ACE values were observed in # 3%.
a. ACE increases occurring in colorectal cancer.
ACE increases were correlated with disease stage. ACE increases in excess of 5 ng / mL were observed in approximately 4% of patients with Dukes ‘stage A’, 25% of patients with stage B, 45% of patients with stage C and at 65% of patients with colon cancer metastatic, especially metastatic disease in the liver, or bone or lung (Gold P 1965). ACE is not specific enough to be used in screening or diagnostic purposes.
ACE has normal levels of tumor markers <5 ng / ml.
Patients who had higher ACE levels of 10ng / ml before applying treatment have a much worse prognosis than patients with values lower than 10 ng / ml. (Ladenson JH 1980 Wanebo HJ 1978).
Currently NCI believes that ACE is available noninvasive technique for detecting patients disseminate relapse surveillance of colorectal cancer. Lowering blood is indicative of effective therapy ACE and ACE indicate increasing levels of disease activity, although increased ACE may precede clinical symptoms of relapse by months (Wanebo HJ 1978). A similar deposition can be done for patients with lung cancer and breast cancer.
ACE increases do not occur in all patients who present relapse. A positive or increase is significant, but normal values do not exclude a tumor recurrence
b. ACE is a marker of breast cancer and is increased to 60% of women with metastatic disease (Schwartz MK 1967).
As with colon cancer, breast cancer ACE increases correlate with disease extent and location of metastases.
An examination of the data in the four studies have shown abnormal values at 9% (0-15%) of 194 patients with stage I disease, 23% (0-43%) in 237 patients with stage II disease, the 45% (31-64%) of 102 patients with stage III disease and 58% (29-100%) of 2171 patients with stage IV disease (DT Kiang 1990).
A summary of the ACE in assessing relapse included 13 studies comprising 1626 patients with breast cancer. Of these patients 312 (19%) experienced recurrences. The headquarters of recurrence or relapse was whether local or disseminated was not specified. Of these 312 patients 107 (47%) displayed a high levels of ACE 1-31 months before the occurrence of relapse. In 120 (53%) other patients there were no increases in the ACE documentation before relapse. These patients were declared false negative (DB Beard 1986).
Antigen CA 15-3
The marker which caused most interest and for which there is the greatest amount of information is CA15-3, a glycoprotein of 300-450 kd.
Tumor marker CA 15-3 is normal <35 U / ml
CA 15-3 is elevated in only 20% of primary breast cancer patients, but increases to 61% -84% of metastatic breast cancer patients, especially in patients with bone metastases. (Hayes DF 1986 R 1989 Colomer ).
In liver metastases Ca15- 3 was increased to 79%. In bone metastases, CA15- 3 was increased to 71% of patients.
CA15-3 increases were observed in 8% of women with benign breast disease and 30% of patients with hepatitis.
It cannot be used for screening or initial diagnosis, but it is a very good marker for monitoring patients with recurrent disease. He drops during therapy and increases effective CA15-3 clinical signs appear before the emergence of relapse.
CA15- 3 was significantly related to the extension of metastases, number of metastatic offices and survival.
In a study on 205 women who had recurrences at 8-289 months after initial treatment, 22% of patients there was no increase in markers, CA15- 3 was increased to 28% of patients (Safi F 1991) .
Elevated levels decreased to 78% of patients with disease regression. And have not changed in 59% of patients with stable disease (R Colomer 1989).
In addition there are other CA15-3 antigen in the membrane of the breast cancer including CA549, CA M26, M29 CA, CA27.29, and mWS. When comparing these antigens (including CA15-3), it was found that all exhibit negative predictive values of 50% -52% and positive predictive values between 88% and 100%. (Dnistrian AM 1991 AM Dnistrian, Schwartz MK 1991).
CA -125 is normal <35 U / ml. It is secreted by the epithelial tumors standard tumor marker in the evaluation of a pelvic tumor mass.
In postmenopausal women with pelvic tumors and elevated CA-125 is recommended laparotomy.
In premenopausal women values exceed 65-200U CA -125 / ml to differentiate a benign cyst from a malignant cyst.
In functional ovarian cysts CA-125 level is stable or decreasing while CA-125 values malignant cysts grow during follow-up (Morton K Schwartz 1993).
FDA has approved its use in monitoring patients treated for ovarian cancer.
Increases> 35 U / ml were reported (Morton K Schwartz 1993):
– 1% of normal women
– 0% -6% of women with benign disease (pregnancy, pelvic inflammatory disease, endometriosis)
– 82% of patients with ovarian cancer
– 21% of patients with colorectal cancer
– 12% of patients with breast cancer
– 32% of lung cancer patients who
– 59% of patients with pancreatic cancer
The level of CA-125 is elevated in 80% of women with advanced ovarian cancer. It is useful when preoperative and postoperative assessment was increased confirm or deny effective therapy.
It is used as an aid in detecting residual disease in patients with cancer who were treated ovrian first-line chemotherapy. A level greater than 35 U / ml is predictive of residual disease. A positive value indicates the presence of residual disease CA 125, but normal values do not exclude the presence of residual disease.
Tumor size influences levels of CA 125
Α-fetoprotein AFP (AFP) yolk sac is produced by fetal liver and gastrointestinal tract. Normal values in adults <15ηg / ml (Morton K Schwartz 1993).
AFP is a marker sheik in:
– Hepatocellular carcinoma
– Non-seminoma testicular tumors (cancers involving elements of yolk sac)
– Benign liver disease
a. AFP is used in screening and detection of hepatocellular carcinoma in patients in Asia. Values of 100-350 ng / ml suggest the diagnosis of HCC, and values> 350ng / ml usually indicate HCC. High levels indicate a poor prognosis (Morton K Schwartz 1993).
b. All seminoma tumors (testicular, ovarian, mediastinal) except AFP producing β-hCG choriocarcinoma.
Persistence both markers after surgery indicates the presence of residual tumor.
Increasing markers after treatment indicates the presence of active disease.
Increased markers in patients who were in clinical remission are a sign of disease relapse (Morton K Schwartz 1993).
PSA (prostate specific antigen) has the normal values η of less than 4 g / ml.
Values of PSA> 10 η g / ml are suspicious of prostate cancer. The difficulty in interpretation occurs in PSA values between 4 and 10 η g / ml in benign conditions that may occur. PSA serum values are not altered by digital rectal examination so PSA analysis can be performed before and after digital rectal examination (Morton K Schwartz 1993).
Approximately 25% of patients with biopsy proven prostate cancer have normal PSA levels. The PSA values of 4-10 η g / ml trans-rectal ultrasonography if associated with?% 8 # and prostate biopsy, prostate cancer is detected in 20% of patients, and PSA levels greater than 10 η g / ml 60% of patients.
PSA was found increased in prostate cancer:
– 35% A stg
– 60% in stg B
– 86% in stg C
– 77% in stg D
PSA can be used in monitoring therapeutic response.
Increased PSA may precede relapse.
After surgery a marked decrease in PSA levels confirm removing cancer.
PSA levels correlate with tumor volume.
The PSA levels <10 η g / ml tumors limited to the prostate capsule.
The PSA value of 50 η g / ml or more appears seminal vesicle invasion and pelvic lymphadenopathy.
Values of PSA> of 100η g / ml is associated with disseminated disease.
There is NO conclusive data to recommend routine use of prostate cancer screening. ACS recommends annual PSA TR and in patients> 50 with a life expectancy greater than 10 years after the needles only discuss with the patient the benefits and drawbacks of these tests (Morton K Schwartz 1993).
Tumor markers are substances as determined by biochemical or immunochemical in tissues or body fluids to detect cancer and possibly the organ, to determine the tumor burden prior to treatment and to monitor response to treatment.
Most used are CA 15-3, CA 125, ACE, PSA, AFP
It is recommended for monitoring patients with cancer treated for early detection of recurrence.
They are not useful in screening.
The only marker in screening is widely used PSA (prostate specific antigen)