Table of contents :

mass screening : that performed on or made available to an entire population.

• multiphasic or multiple screening : that in which various diagnostic procedures are employed during the same screening program.
• prescriptive screening : that performed for the early detection of disease or disease precursors in apparently well individuals so that health care can be provided early in the course of the disease or before the disease becomes manifest

• cost
• efficacy
• technical modalities
• uninvasivity
• psychological consequences

• predisposition markers
• early disease stages markers
• prenatal diagnosis
• echography
• neural tube diseases (NTDs)
• anencephalia
• hydrocephalia
• spina bifida
• cranial-skeletal malformations
• teratomas
• cystic hygromas
• alterations in limb length
• biliary tract malformations :
• biliary tract atresia
• choledocus cyst
• urinary malformations
• polycystic kidney
• multicystic kidney
• renal agenesis
• hydronephrosis
• megaloureter
• megabladder
• ureterocele
• vesical exstrophy
• gastrointestinal malformations
• esophageal atresia
• duodenal atresia
• jejunoileal atresia
• colonic atresia
• congenital diaphragmatic hernia (CDH)
• abdominal wall malformations :
• omphalocele
• gastroschisis
• pulmonary malformations
• pulmonary hypoplasia
• congenital pulmonary airway malformation (CPAM)
• congenital cystic adenomatoid malformation (CCAM)
• bronchial or bronchogenic cyst
• genital malformations
• ovarian cysts
• neoplasms
• tumors
• childhood renal cancers (Wilms' tumor)
• PNS neuroblastoma
• hepatic hemangioendothelioma
• pelvic or sacrococcygeal teratoma
• prenatal genetic diagnosis (see also diseases with intrinsic aetiology and preimplantation genetic diagnosis (PGD))
• retrieval of trophoblast cells from the cervical mucus^ref
• maternal blood
• Triplo test ([hCG, estriol, and a-FP]_{maternal plasma} at a given maternal age) at pregnancy wk 15-17 for prenatal screening of Down syndrome => if specific risk is > 1:350 or age > 35 yrs => amniocentesis or chorionic villus sampling (CVS) (5% of all pregnants; sensitivity = 70-90%). Poor specificity in multiple pregnancies and maternal diabetes mellitus
• gene testing :
• single-allele base extension reactions and mass spectrometry (MS) allows for the reliable detection of fetal-specific alleles, including point mutations and SNPs, in maternal plasma and could pave the way for prenatal diagnosis by a simple and safe test. Although the blood of a mother and fetus do not mix directly, the placenta sheds about 8 grams of tissue a day, releasing the baby's DNA into the mother's blood.
• fetal erythroblasts : the first report of the occurrence of fetal cells in maternal circulation dates back to 1893 when the German pathologist Schmorl identified trophoblast cells in the lungs of women who had died from eclampsia^ref. Approximately 50% of the enriched erythroblasts in maternal blood are of fetal origin^ref. Although apoptotic intact fetal cells could contribute to the detection of fetal DNA in maternal plasma, recovery of these cells is difficult and not clinically practical^ref. The traffic of fetal erythroblasts into the maternal peripheral circulation is enhanced in the second trimester of pregnancy, well before the onset of pre-eclampsia symptoms^ref, but not before onset of preterm labor^ref. Fetal hemopoietic progenitor cells from maternal blood cannot be clonally expanded^ref.
• while circulating fetal cells are present only in < 1 in a million cells, 3 to 5% of the DNA in the cell-free plasma of the mother comes from the fetus. Cell-free fetal DNA in the maternal circulation does not stem from the transplacental passage of fetal erythroblasts : an alternative cell type is the source of cell-free fetal DNA. Furthermore, it appears that the release of cell-free fetal DNA from this cell type is affected by pathological placental conditions which are not associated with an increase in fetal cell trafficking^ref. In 2004 Hahn's team found that a mother's DNA fragments tend to be much larger than those of her unborn child. So the researchers separated the maternal and fetal DNA in blood samples using electrophoresis^ref. Elevations in the concentration of cell-free fetal DNA in maternal plasma have recently been determined in various pregnancy-related disorders, including preeclampsia^ref, preterm labor, and polyhydramnios^ref. Circulating fetal DNA in maternal plasma is increased in pregnancies at high altitude^{ref1, ref2} and is further enhanced prior to the onset of preeclampsia^ref. On the contrary it is not possible to detect cell free fetal DNA in the urine of normal pregnant women nor in those affected by preeclampsia associated HELLP syndrome^ref., while urinary cell-free DNA is a marker for kidney graft rejection^ref. In nonpregnant controls the total amount of cell free DNA fluctuated by an average of 13.5-fold. In samples obtained from pregnant women the amount of maternal cell free DNA varied by an average of 21.5-fold. Because ten of those women were pregnant with male fetuses, the concentration of free fetal DNA in these cases was determined by a real-time PCR assay for the Y chromosome. The mean variation in free fetal DNA levels in male fetuses was 2.2-fold^ref. Almost 2-fold increments in cell-free fetal DNA levels have been recorded in pregnancies with certain aneuploid fetuses, in particular trisomy 21. Severalfold alterations in circulatory DNA amounts do occur over short periods of time. Of particular note is that almost 2-fold variations in free fetal DNA levels are observed over a period of 3 days, which are in a similar range to the elevations noted in aneuploid pregnancies^ref.
• when the approach was applied to diagnose the fetal inheritance of the 4 most common Southeast Asian b-thalassemia mutations (approximately 2.5% of Chinese in Hong Kong carry it) at 7 to 21 weeks' gestation, fetal genotypes were correctly predicted in all cases studied. Previous attempts used fetal erythroblasts enriched from maternal blood by a novel gradient^ref. Detection or exclusion of the paternally inherited mutant allele in maternal plasma as a means of diagnosing these disorders has until now only been possible if the maternal and paternal mutations were different. Even amniocentesis can require paternal blood to establish certain point mutations. Previous attempts to use real-time PCR were abandoned because of the problem of mispriming with an allele-specific primer. Its developers believe that the technique could be applied to a range of other diseases, overcoming the need for amniocentesis. Screening a mother's blood can already determine whether unborn children have certain hereditary diseases. The researchers took blood samples from 32 women of southern Italy who were about 12 weeks into their pregnancies. Family histories suggested that the babies were at risk of being born with b-thalassemia, a fatal hereditary disease that stops red blood cells producing haemoglobin. The smallest fragments were almost entirely from the fetus, allowing the researchers to correctly identify the presence or absence of b-thalassemia mutation 93.8% of the time^ref. The gene responsible for b-thalassemia is recessive, so a parent can carry one copy of the gene mutation without having the disease. But if a child receives 2 mutated copies, one from each parent, he or she will ultimately develop the disorder. There are > 200 known mutations of the crucial gene, any combination of which will lead to b-thalassemia. Despite the difference in fragment size, there is still a risk that the 'fetal' DNA could in fact belong to the mother, so finding that it contained her particular genetic mutation would not be conclusive. Instead, the researchers search for evidence that this DNA contains the father's mutation
• cystic fibrosis
• Tay-Sachs disease
• achondroplasia^ref
• rhesus D (fetal DNA from rhesus D positive fetuses is present in maternal plasma even after prophylactic anti-D treatment)^{ref1, ref2}
• pregnancies with aneuploid fetuses (mean of 7% in aneuploid samples versus 3.5% in normal pregnancies)^{ref1, ref2, ref3}
• use of the technology for prenatal sex selection would be unacceptable.

maternal age	Down syndrome risk	all chromosomal anomalies risk
20	1/1667	1/526
25	1/1250	1/476
30	1/952	1/385
35	1/385	1/202
36	1/295	1/162
37	1/227	1/129
38	1/175	1/102
39	1/137	1/82
40	1/106	1/65
42	1/64	1/40
45	1/30	1/20

Web resources : Newborn Screening at CDC
• postnatal screening :
• infantile hypothyroidism
• phenylketonuria
• galactosemia
• cystic fibrosis
• multiple carboxylase deficiency
• congenital adrenal hyperplasia (CAH)
• Chlamydia : every 1-2 years in women aged 18-25 years
• diagnosis of cardiovascular diseases
• screening treadmill for a 50-year-old (asymptomatic) man (estinmated average increase in life expectancy for a population : 8 days)
• blood pressure, height, and weight : periodically after age 18
• cholesterolemia : every 5 years in men aged > 35 and women aged > 45 years
• diabetes : every 3 years in people aged > 45 years or earlier, if there are additional risk factors
Web resources : Screening : Vascular Diseases
• cancer diagnosis

 

		US Preventive Services Task Force (USPSTF)	American Cancer Society (ACS)	Canadian Task Force on Prevention Health Care (CTFPHC)	estimated average increase in life expectancy for  a population
lung carcinoma	chest spiral CT scans
	chest X-ray
	measure the presence of organic compounds in your breath : a pattern of 9 compounds predicted 85% of lung cancers
breast cancer (lifetime cumulative risk = 10%)	breast self-examination (BSE) : mainstream BSE education uses messages that deemphasize the woman, her breasts, and her relationship to them as sexual. The turbid confluence of societally eroticized breasts and self-touch taboos makes it unlikely that women filter these messages in an asexual way. The examination should be ideally practiced 48-72 hours after end of each menstruation since age 20, looking for breast asymmetry, retraction of skin or nipple, orange-peel skin, nodules, or nipple secretions : practice during ovulatory or premenstrual stage has poor specificity due to physiological increase in tenderness and nodularity	no recommendation	>= 20, monthly	insufficient evidence to make a recommendation
	breast clinical examination	females > 50 years, every year	females aged 20ò40 years, every 3 years; > 40, yearly	females > 50 years, every year
	mammography (sensitivity = 36-90%) : 1 per year in ages 40-50; 1 every 2 years after age 50	females 40-75, every 1-2 years	females > 40, every year	females 50-69, every year	women, 40-50 years = 0-5 days women, 50-70 years = 1 month
	echography (specificity = 90% for fibroadenomas, 70% for carcinomas)
	FNAB (sensitivity = 87%; specificity = 100%; positive predictive value = 100%; negative predictive value = 60-90%)
	MRI (sensitivity = 96%)
	CA15-3
	BRCA1 or BRCA2 sequencing
	ductal lavage
ovarian carcinoma	transvaginal echography
	CA-125 (sensitivity < 50%)
cervical carcinoma (lifetime cumulative risk = 2%)	Pap smear and gynaecological visit :	females aged 18-65 : every 1-3 years	females with uterine cervix, beginning 3 years after first intercourse or by age 21. Yearly for standard Pap; every 2 years with liquid test in USA : 1 yr after first sexual intercourse, 6-12 months after the first, then 1 every 3 years in Italy : 1 per year for 3 years after first sexual intercourse, then 1 every 3 years	fair evidence to include in examination of sexually active women	age 18-65 : 2-3 months
	pelvic examinations	do not recommend, advise adnexal palpation during exam for other reasons	females aged 18-40, every 1-3 years with Pap test; >40, every year	not considered
	endometrial tissue sampling	not considered	at menopause if obese or a history of unopposed estrogen use	not considered
testicular cancer	monthly testicular self-palpation
	yearly testicular echography
colorectal carcinoma (CRC) (lifetime cumulative risk = 6%) : screening patients unlikely to live long enough to develop and die from CRC provides no benefit and places these individuals at unjustifiable risk. Additionally, inappropriate screening utilizes resources that could be used to improve screening and follow-up for eligible individualsref	faecal occult blood tests (FOBT) (Hemoccult II) tests for hidden blood in a stool specimen after meat-less diet. Guaiac-based FOBT has an estimated programme sensitivity of > 60% but < 30% for strictly asymptomatic CRC in a single screening round (should be repeated at least 6 times)	>= 50 years, every year	>= 50 years, every year	insufficient evidence
	optic fiber or virtual rectosigmoidoscopy. If a lesion is found, practice pancolonoscopy. Many patients, cringing at the very thought of a colonoscopy, don't submit to one -- < 40% of people aged > 50 undergo screening	> 50 years, periodically < 50 years not recommended	>= 50 years, every 3-5 years (colonoscopy every 10 years)	insufficient evidence
	digital rectal examination	no recommendation	>= 40 years, every year	poor evidence to include or exclude
	stool test that doesn't find blood but instead detects mutated DNA shed (sensitivity = 70%). A comparison of a fecal DNA test with the standard fecal occult blood test found that more cancers were detected using the DNA screening. However, neither test found > 41% of the invasive cancers and benign polyps. In addition, the cost of the fecal DNA test is much higher than the occult blood test, and approaches the cost of a colonoscopy.
	a universal screening program for the detection of microsatellite instability in patients with colorectal cancer is feasible and probably desirable. However, it would cost in excess of $57,000 per germ-line–mutation carrier detected. Furthermore, the benefits to the proband are modest, since neither treatment nor outcome is likely to change on the basis of test results. The cost-effectiveness of such a program thus depends heavily on the ability to locate and test relatives, since they have higher riskref
prostate adenocarcinoma	[PSA]serum => transrectal echography. Men should get a baseline test at age 35 or 40 so doctors can monitor changes over time. Current guidelines call for annual PSA tests beginning at age 50 (or 40-45 for African Americans and men with a family history of prostate cancer) to men who have a life expectancy of at least 10 years : this includes men up to age 76 years	insufficient evidence to recommend	males aged > 50 years : every year	recommendation against	> 50 years : up to 2 weeks
	digital rectal exploration (DRE)		males aged > 50 years : every year
melanoma	complete skin examination	not recommended	20-39 years, every 3 years	poor evidence to include or exclude

• getting a 35-year-old smoker to quit : estimated average increase in life expectancy for a population : 3-5 years !
• beginning regular exercise for a 40-year old man (30 min 3 times a week) : estimated average increase in life expectancy for a population = 9 months to 2 years !
Tumor markers are nowadays at the centre of attention in the screening, diagnosis (rarely), monitoring of the effect of therapy, prognosis and long-term monitoring aimed at early detection of progression and generalization of the disease of patients with malignant diseases. They can be detected either histochemically ...
• directly in the tumor cell (cellular tumor markers)
• in body fluids (humoral tumor markers)
The ideal tumor marker :
• used in screening :
• high sensitivity
• high specificity
• delineation of cell type of origin. Organ specificity during the assessment of one isolated marker is relatively low, and it increases mainly by using combinations of tumor markers.
• primary marker : first choice marker with high sensitivity and specificity for the given type of tumor.
• secondary marker : second choice marker which is usually assessed in parallel with the first choice marker. It has a lower sensitivity and a lower specificity for the given tumor but in combination with the primary marker it increases the detection of a particular tumor.
• additional marker : relatively low sensitivity and specificity for detecting malignant disease but is usually specific for the particular organ (therefore it can have a high organ specificity). In addition, its positivity tends to be a signal of tumor generalisation.
• prognostic information
• monitoring :
• cure
• progression
• markers :
• reproducible
• unexpensive
• rapid
• meeting patient compliance

	tumor markers	biological half-life	produced by	normal values and material for assessment	borderline values in serum or plasma	pathological values in serum or plasma	decreased values in
oncofoetal antigens	carcinoembryonic antigen (CEA) family comprises 29 genes tightly clustered on the long arm of chromosome 19 of which 18 are expressed. It is an important tumor marker for colorectal carcinomas and some other carcinomas (including breast carcinomas). The CEA family members contain immunoglobulin-like domains in their basic structures  CEA subgroup members are either membrane bound through a GPI anchor, or are integral membrane proteins and show a complex expression pattern in normal and cancerous tissues with notably CEA showing a selective epithelial expression. It is expressed in various adenocarcinomas, epithelia lining the gastrointestinal tract, in eccrine sweat glands, lung epithelia and testes non-specific cross-reacting antigens (NCAs) are often coexpressed with CEA, but are also found in granulocytes. CEA-like 1 (CEAL1) carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) / biliary glycoprotein I (BGPI) / CD66A : functions in signal transduction possibly in association with other CEA sub-family members; modified ITAM/ITIM motif in the cytoplasmatic domain CEACAM3 CEACAM4 CEACAM5 CEACAM6 CEACAM7 CEACAM8 pregnancy specific b1-glycoproteins (PSGs) subgroup are coexpressed in syncytiotrophoblast cells of the placenta, submandibular salivary glands and fetal liver, as well as in choriocarcinomas and breast carcinomas. They are secreted from the cell PSG1 PSG2 PSG3 PSG4 PSG5 PSG6 PSG7 PSG8 PSG9 PSG10 CEA is a glycoprotein with the molecular mass of 180 kDa which consists of saccharides (55%) and by proteins (45%). High molecule heterogeneity is caused by the heterogeneity of the saccharide component, and the protein component is constant	14 days (metabolized in the liver)	in adults it is produced only in a very limited amount by epithelial cells particularly of the digestive tract (highest concentrations are found in the salivary glands and their ducts), mammary glands and bronchi : minimal concentrations in blood, pleural exudate, ascites and CSF. In the first trimester it is contained in cytoplasm. In later phases of foetal development it is a part of the cell membrane surface	serum or plasma (0–5 ng/mL)  thoracic exudate  ascites  cellular cytosol  articular exudate  cystic fluid (breast, ovary)	5 – 8 ng/mL (0-5 ng/ml)	> 5 ng/mL  adenocarcinomas :  esophageal adenocarcinoma gastric adenocarcinoma colorectal adenocarcinoma breast adenocarcinoma ovarian adenocarcinoma uterus adenocarcinoma lung adenocarcinoma cholangiocarcinoma prostate adenocarcinoma tobacco smokers chronic renal failure chronic kidney disease  chronic hepatitis chronic pancreatitis ulcerative colitis Crohn's disease bronchopneumonia chronic bronchitis pulmonary tuberculosis cystic fibrosis autoimmune diseases  in the fluid of breast and ovarian cysts in the articular fluid in rheumatoid arthritis
	a1-fetoprotein (AFP) is a glycoprotein with a molecular mass of approximately 70 kDa that substitutes for albumin and its transport functions in the foetus. It consists mainly of proteins, and it contains only 4.5% saccharides.	3-6 days	trophoblastic mononuclear cells,  vitelline sac and later by the liver of the fetus (highest between the 10th and 13th week of pregnancy = 3g/L, decreases gradually towards the term of delivery = 80mg/L), pancreas, lung,	serum or plasma (< 10 mg/mL; maximal value 1-2 months before childbirth =. 400 mg/L), thoracic exudate,  ascites,  cystic fluid (ovary),  amniotic fluid (1/100 of fetal plasma),  bile	5 – 10 IU/mL or 0-10 ng/ml in pregnancy :  first trimester : 11-119 ng/ml second tirmester : 96-302 ng/ml third trimester : 103-550 ng/ml pediatric : week 0-1 : 5,000-105,000 ng/ml week 2-month 1 : 300-60,00 ng/ml month 1 : 100-10,000 ng/ml month 2 : 40-1,000 ng/ml month 3 : 11-300 ng/ml month 4 : 5-200 ng/ml month > 6 : 0-15 ng/ml	> 10 IU/mL  yolk sac tumor (YST) (50%) ataxia teleangiectasia hepatoblastoma (100% of patients) hepatocellular carcinoma (80%; with the exception of anaplastic Ca which is AFP negative)  liver metastases (lung adenocarcinoma, breast adenocarcinoma, and colorectal adenocarcinoma)  ovarian adenocarcinoma testicular cancers gastric adenocarcinoma intestinal adenocarcinoma pancreatic adenocarcinoma breast adenocarcinoma bronchial tumors acute viral hepatitis chronic hepatitis liver cirrhosis chronic renal failure hypertyrosinemia in pregnancy only : multiple pregnancy intrauterine fetal death fetal congenital nephrosis	\
	b subunit of hCG	1.5 – 2.5 days	pancreas, lung, breast, kidney, bladder, syncitiotrophoblastic cells (since day 5-8 of conception to day +8-11 after delivery) => blood and urine	serum or plasma (0 – 5 IU/L)  amniotic fluid,  urine,  CSF	5 – 10 IU/L pregnancy :  week 3-4 : 9-130 mU/ml week 4-5 : 75-2,600 mU/ml week 5-6 : 850-20,800 mU/ml week 16-18 : 20,00-40,000 mU/ml	> 10 IU/L or > 2.01 multiplies of medium (MoM) at a given pregnancy week, maternal weight and number of fetuses : marijuana addicted  pregnancy (syncitiotrophoblastic cells of the placenta) ovarian adenocarcinoma testicular cancers choriocarcinoma (syncitiotrophoblastic cells) hydatiform mole gastric adenocarcinoma hepatocellular carcinoma colorectal adenocarcinoma renal cell carcinoma SCLC (ectopic secretion)  breast adenocarcinoma (ectopic secretion)  uterus body carcinoma menopause leiomyoma uteri ovarian cysts
	prostate specific antigen (PSA) and PSA-linked molecule (PSA-LM) is a glycoprotein with the molecular mass of 34 kDa, 90% of which consists of a simple polypeptide chain of 238 amino acids, and 10% of saccharides; it is a serine protease, responsible for liquefying seminal coagulum PSA density (PSAD) is determined by dividing the PSA level by the size or volume of the prostate) PSA velocity	2-3 days (7 hrs for fPSA)	prostatic fluid, seminal plasma, paraurethral glands, and it may also occur in very low concentrations in women (amniotic fluid, breast milk, breast cyst fluid, nipple aspirate fluid, and breast tumor cytosolref).  In serum it is present in 3 main forms : free (fPSA) bound to a1-antichymotrypsin  bound to b2-macroglobulin (immunologically non-detectable)	serum or plasma (< 4 ng/mL),  cytosol,  cystic fluid (breast)	4-10 ng/mL  age 40-49 : < 2.5 ng/ml age 50-59 : < 3.5 ng/ml age 60-69 : < 4.5 ng/ml age 70-79 : < 6 ng/ml free PSA (fPSA) :  0-15% = malignant tumor 15-20% = borderline cases > 20% = benign disease	race 3 polymorphisms, present in about 20% of the subjects (30% higher) TURP prostate biopsy prostatitis prostate infarction ejaculation aging (decreased renal clearance)  mechanical irritation of the prostate (catheterization, cystoscopy)  and vigorous prostate massage : in general, DRE does not increase serum PSA (although if serial PSA values are being done annually, it is generally best for DRE to follow phlebotomy). BPH : < 4 ng/mL by using Hybritech, with fPSA > 14% prostate adenocarcinoma, with fPSA < 14%. It is used for screening, follow up after radical prostatectomy (concentration falls within 2-3 weeks), radiotherapy and androgen suppression. lung adenocarcinoma colorectal adenocarcinoma breast adenocarcinoma hepatocellular carcinoma adrenal carcinoma	complete androgen block 5a-reductase inhibitors (50% reduction) BPH surgery radical surgery
	carbohydrate antigen (CA15-3) is a monoclonal antibody defined tumor marker of mucin glycoprotein structure, with a molecular mass of 300-450 kDa.	7 days	In the foetus it occurs in the epithelial cells of the bronchi and liver. In adults it represents a surface antigen of glandular cells in the mammary gland ducts which is oriented into the glandular duct lumen.	serum or plasma (0 – 22 IU/mL),  thoracic exudate,  ascites,  CSF,  cystic fluid (breast, ovaries)	22 – 30 IU/mL (0-25 U/ml)	> 30 IU/mL  breast adenocarcinoma lung adenocarcinoma gastric adenocarcinoma hepatocellular carcinoma pancreatic adenocarcinoma ovarian adenocarcinoma endometrial adenocarcinoma benign breast disease  benign digestive tract disease  liver cirrhosis chronic renal failure (mainly in hemodialysis therapy)  HIV-1 pneumonia and bronchopneumonia chronic bronchitis pulmonary tuberculosis acute hepatitis chronic hepatitis rheumatic diseases  physiologically during pregnancy
	carbohydrate antigen (CA125) / M17S2 is a mAb- defined tumor marker of mucin glycoprotein nature, with a molecular mass of about 200 kDa	4 days	In the foetus it occurs in the epithelial cells of the respiratory and digestive tracts. In adults, similarly to the foetus, it occurs in the epithelial cells of respiratory tract. Considerably raised levels are found in the serum of pregnant women and in breast milk.	serum or plasma (0 – 30 IU/mL), CSF	30 – 40 IU/mL (0-35 IU/ml)	> 40 IU/mL  mesotheliomas :  germinal epithelial tumors  pleural mesothelioma endometrial adenocarcinoma breast adenocarcinoma pancreatic adenocarcinoma hepatocellular carcinoma colorectal adenocarcinoma gastric adenocarcinoma lung adenocarcinoma liver metastases benign disease of ovaries and endometrium leiomyoma uteri renal insufficiency acute pancreatitis acute hepatitis liver cirrhosis icterus biliary cirrhosis physiologically during pregnancy
	carbohydrate antigen (CA19-9) / gastrointestinal cancer-associated antigen (GICA) / monosialyl Lewis (a) antigen is a ganglioside, component of cellular wall, with a Mr > 500 kDa, defined by a mAb	5 days	in the rarely occurring Lewis (a-/b-) blood group this tumor marker is not produced.  In the foetus it occurs in the epithelial cells of, in particular, the digestive tract, pancreas and liver. In adults it is produced only to a very limited extent by the epithelial cells of the bronchi and digestive tract. In minimal concentrations it occurs in blood, pleural exudate, ascites, and in cerebrospinal fluid. CA 19-9 is eliminated exclusively by bile.	serum or plasma (0 – 30 IU/mL),  thoracic exudate  ascites	30 – 40 IU/mL (0-37 IU/ml)	>  40 IU/mL  pancreatic adenocarcinoma gallbladder carcinoma biliary tract cancers hepatocellular carcinoma gastric adenocarcinoma colorectal adenocarcinoma breast adenocarcinoma ovarian adenocarcinoma (mainly mucinous type)  uterus adenocarcinoma liver metastases of all mentioned carcinomas  In little differentiated carcinomas its production reduces, and in anaplastic carcinomas it is missing altogether.  liver cirrhosis primary biliary cirrhosis acute hepatitis chronic hepatitis cholecystitis cholangitis choledocholithiasis benign stomach diseases  acute pancreatitis chronic pancreatitis ulcerative colitis Crohn's disease
	carbohydrate antigen (CA72-4) is a monoclonal antibody defined glycoprotein of mucinous type with a molecular mass of about 400 kDa.		surface epithelial structures of the oesophagus, stomach and pancreas of the developing foetus, and to a very small extent also of healthy adults.	serum or plasma (0 – 3 ng/mL),  thoracic exudate,  ascites	3 – 6 ng/mL	> 6 ng/mL  esophageal adenocarcinoma gastric adenocarcinoma pancreatic adenocarcinoma biliary tract cancers colon carcinoma hepatocellular carcinoma ovarian adenocarcinoma (mainly mucinous)  colorectal adenocarcinoma endometrial adenocarcinoma breast adenocarcinoma lung adenocarcinoma liver metastases of all mentioned carcinomas  liver cirrhosis acute pancreatitis chronic bronchitis bronchopneumonia and pneumonia stomach ulcer inflammatory disease of digestive tract
	carbohydrate antigen 50 (CA50) / tumor-associated gangliosidic antigen is a monoclonal antibody defined mucin-glycolipid antigen, similar in structure to CA 19-9.		present in meconium, very small amount in stomach, gallbladder and pancreas epithelium in healthy adults.	serum or plasma (0 – 10 IU/mL),  thoracic exudate,  ascites	10 – 14 IU/mL	> 14 IU/mL  esophageal adenocarcinoma gastric adenocarcinoma pancreatic adenocarcinoma biliary tract cancers colon carcinoma hepatocellular carcinoma ovarian adenocarcinoma  (mainly mucinous)  cervical carcinoma endometrial adenocarcinoma breast adenocarcinoma lung adenocarcinoma liver metastases of all mentioned carcinomas  liver cirrhosis acute pancreatitis chronic pancreatitis acute hepatitis chronic hepatitis cholecystitis cholangitis stomach ulcer
	carbohydrate antigen 242 (CA242)
	squamous cell carcinoma (SCC) antigen 1 / SERPINB3 is a glycoprotein with a molecular mass of 48 kDa	20'	tile-like epidermoid cells of the foetus and adults. SCC is present in the middle layers of the epithelium.	serum or plasma (0 – 1.5 ng/mL),  thoracic exudate,  ascites	1.5 – 2 ng/mL	> 2 ng/mL  lung adenocarcinoma cervical carcinoma endometrial adenocarcinoma vulvar carcinoma vaginal carcinoma  breast adenocarcinoma tongue carcinoma stomodaeum  cheilocarcinoma laryngeal carcinoma esophageal carcinoma non-tumor lung diseases  renal insufficiency chronic liver diseases  physiologically during pregnancy
	neuron specific enolase (NSE)			serum or plasma (0 – 10 ng/mL),  thoracic exudate  ascites  cystic fluid	10 – 12,5 ng/mL or mg/L	> 12,5 ng/mL  primitive neuroectodermal tumor (PNET) medulloblastoma medulloblastoma  retinoblastoma  melanoma tumors of neuroendocrine origin  medullary thyroid carcinoma  carcinoid  pheochromocytoma  small cell lung carcinoma (SCLC) seminoma renal cell carcinoma benign lung diseases  renal insufficiency benign liver diseases  During long standing of whole blood at laboratory temperature, or at temperature of 4-8°C, NSE levels significantly increase non-specifically!
	thymidine kinase (TK)					melanoma melanoma colorectal adenocarcinoma biliary tract cancers liver metastases breast adenocarcinoma small cell lung carcinoma (SCLC) non-small cell lung carcinoma (NSCLC) testicular cancers prostate adenocarcinoma choriocarcinoma leukaemia and lymphomas
	tissue polypeptidic antigen (TPA) and tissue polypeptidic specific antigen (TPS) are cytokeratin subunit fragments released into body fluids during the proliferation of tumor cells or cellular necrosis.  TPA assessment is based on the fragment detection of cytokeratin 8, cytokeratin 18 and cytokeratin 19 TPS assessment detects only fragments of cytokeratin 18 and cytokeratin 18	7 days	trophoblast in the placenta, liver, lungs, intestine and kidneys of a developing foetus. In healthy adults TPA and TPS can be found in the epithelium of the mammary gland ducts, in the bladder, lungs, and in organs of the digestive tract.	serum or plasma (TPA : 80 – 120 IU/mL or < 85 U/l; TPS : 0 – 85 IU/mL or < 35 U/l),  thoracic exudate,  ascites, cellular cytosol,  articular exudate, cystic fluid,  urine	TPA : 120 – 140 IU/mL TPS : 85 – 95 IU/mL	TPA > 140 IU/mL  TPS > 95 IU/mL  breast adenocarcinoma tumors in the orofacial area  colorectal adenocarcinoma hepatocellular carcinoma pancreatic adenocarcinoma testicular cancers prostate adenocarcinoma thyroid carcinoma lung adenocarcinoma renal cell carcinoma ovarian adenocarcinoma hepatitis liver cirrhosis diabetes mellitus respiratory tract infections  benign breast diseases  benign diseases of the digestive tract  post-surgical conditions  rheumatic diseases  immuno-alteration diseases
	CYFRA 21-1 assessment is based on fragment detection of cytokeratin 19, an acid protein with a molecular mass of 40 kDa.		cells of lung tissue, the uterus and the digestive tract.	serum or plasma (0 – 2,5 ng/mL), thoracic exudate,  ascites,  cellular cytosol,  cystic fluid	2.5 – 3.5 ng/mL	> 3,5 ng/mL  non-small cell lung carcinoma (NSCLC) cervical carcinoma breast adenocarcinoma bladder carcinoma ovarian adenocarcinoma esophageal adenocarcinoma rectal carcinoma liver cirrhosis chronic renal failure asthma pulmonary tuberculosis respiratory tract infections
	b2-microglobulin	40'	all cells (higher on B-lymphocytes, plasma cells, macrophages and endothelial cells) with the exception of erythrocytes and trophoblastic cells.	serum or plasma (0 – 1,5 mg/L),  thoracic exudate  ascites  cystic fluid	1.5 – 2.5 mg/L in serum 0-16 mg/l or 0-30 mg/g creatininemia in urine 0-2,4 mg/l in CSF	> 2,5 mg/L  leukaemia and lymphomas multiple myeloma inflammatory processes  massive cellular necrosis (during tumor chemotherapy and radiotherapy) chronic liver and kidney diseases  renal insufficiency, mainly in haemodialysis therapy
	colon cancer secreted protein-2 (CCSP-2)					transcript generally absent in normal colon and other normal body tissues, but that is induced an average of 78-fold in Stage II, III, and IV colorectal carcinoma (CRC), as well as in colon adenomas and colon cancer cell lines. Moreover the protein is found in serumref
	mucin-like carcinoma-associated antigen (MCA)				< 17 U/ml	breast carcinomas
	tumor-associated antigen 72 (TAG72)
	calcitonin		parafollicular cells of thyroid		< 11.5 pg/ml	medullary thyroid carcinoma carcinoid pheochromocytoma PNS neuroblastoma
	ferritin				6 months : 7-430 ng/ml 1 year : 7-85 ng/ml prepubertal : 60-150 ng/ml adult male : 7-330 ng/ml adult female : 7-280 ng/ml	Hodgkin's disease leukemia hepatocellular carcinoma breast carcinomas non-small cell lung carcinoma (NSCLC) renal cell carcinoma idiopathic hemochromatosis post-transfusion hemochromatosis chronic inflammation	sideropenia
	thyreoglobulin (TG)			0-55 ng/ml		thyroid cancer nodular goitre hyperthyroidism silent thryoiditis

• anti-malignin antibodies (AMA) are IgM spontaneously produced by the host against the 10-kDa oncoprotein malignin when neoplastic transformation occurs : they have been demonstrated in patients with a wide spectrum of non-terminal active cancers, regardless of the anatomical site and histotype of the tumor. The AMA in serum (AMAS^®) test with Target^® reagent is more sensitive (97%) in detecting breast cancer than CEA (0%), CA 15-3 (10%), CA 19-5 (5%) or CA 125 (16%) in the same patients.

Web resources : The AMAS test literature summary
Web resources :
• CDC Health Topics
• Cancer prevention programmes
• Mammograms
• Gastro-intestinal Endoscopy Database
• GeneTests-GeneClinics : genetic testing and genetic counseling
• domestic violence for women (lifetime cumulative risk = up to 15%)
• osteoporosis : periodically in women after age 65 (after age 60 if at risk)
• hip fracture for Caucasian women (lifetime cumulative risk = 16%)
• vision and hearing : periodically after age 65

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