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Détection du cancer et marqueurs tumoraux

 

Pourquoi dépister le cancer
Plus tôt un cancer est diagnostiqué, plus grandes seront les chances de guérison à long terme.
Combien de morts par cancer pourraient-elles être évitées, chaque année, grâce à un véritable dépistage ?
Les estimations varient entre 3 et 35%, selon les sources (NCI, National Cancer Institute : cancer control, objectives for the Nation 1985-2000).

Qui est considéré comme sujet à risque ?
Certains individus sont connus comme étant « sujets à risques », tels ceux qui ont une histoire personnelle de cancer (on recherche là les rechutes), et ceux présentant des cas de cancers dans la famille (à 1 ou 2 degrés de parenté). L’exemple le plus connu est celui de cancer du sein : ce cancer atteignant 1 femme sur 9 au cours de sa vie, toute femme dont la mère, grand’mère, cousine a eu un cancer du sein doit être systématiquement surveillée.
Le fait que les enfants puissent hériter de gênes anormaux augmentant le risque de cancer est bien établi.
Les fumeurs et consommateurs d’alcool augmentent très significativement les risques.
Mais tout un chacun est potentiellement à risque : c’est l’affaire de chacun de se faire dépister.

Progrès dans la détection précoce
Au stade précoce, le cancer peut ne pas présenter de signes. Les marqueurs tumoraux apparaissent dans le sang, en relation avec le développement de certains des plus importants cancers.
La recherche de la présence de ces marqueurs et leur évaluation est utile, car elle signifie qu’un examen médical approfondi doit être entrepris pour confirmer un cancer, et le traiter ensuite.
Pourquoi utiliser des combinaisons de Marqueurs tumoraux, plutôt que des dosages isolés?
Exemple de combinaison : dans "Anticancer Res. 2002 Jul-Aug;22(4):2311-6",
Carpelan-Holmstrom M, Louhimo J, Stenman UH, Alfthan H, Haglund C, disent:
"la combinaison CEA, CA 19-9 and CA 72-4 améliore la qualité du diagnostic dans les cancers gastro-intestinaux."
(Ces marqueurs font partie du Cancersafe®Test).

L'identification et la mesure des marqueurs sont utiles, parce que cela peut détecter la présence de ces substances à un stade précoce, signal qu'il faut pousser l'investigation médicale.
A Cancersafe, nous possédons la vraie expérience de l'utilisation des marqueurs tumoraux.
De plus, avec les résultats, vous obtenez l'opinion de quatre spécialistes, basée sur leur pleine expérience et l'utilisation d'algorithmes spécialement développés : Cancersafe®test est unique.
Pour connaitre le côté technique (comment utiliser plusieurs marqueurs plutôt qu'un isolé) et interpréter les résultats avec des modèles mathématiques, voir "CancerSafe®test".
Quelques références scientifiques pour ces profils :
-"improved sensitivity of fuzzy logic based tumor marker profiles, for diagnosis of Pancreatic Carcinoma", AntiCancer Research 20: 4957-4960 (2000).
-"fuzzy-based multi-parametric analysing methods for the differential diagnosis of Primary lung Cancers", 11th Hamburg Symposium on Tumor Markers, Jan 28th, 2002.
-"tumor markers in the diagnosis of bronchial carcinoma: new options using fuzzy logic-based tumor marker profiles", J.Cancer Res.Clin.Oncol., April 1998.
-"increase of sensitivity by fuzzy-based analysis of tumour marker profiles", 2003, www.isobm2003.org/ws_roche.pdf.

A noter enfin que l'utilisation du couple -imagerie par PET Scan, ou mieux EBT, -et biologie avec marqueurs tumoraux, mérite d'être largement employée : PET Scan a démontré une image de métastases dans 88% des cas suspectés de présenter une maladie métastatique occulte sur la base d'une augmentation significative d'un ou plusieurs marqueurs : sans attendre les symptômes de la maladie métastatique, la thérapie adjuvante prolonge vraisemblablement la survie. Ce concept peut être étendu au traitement des patients paraissant cliniquement exempts de la maladie mais soupçonnés de présenter une maladie occulte déterminée par l'élévation des marqueurs confirmée par le PET Scan.

La stratégie la plus efficace serait donc :
1) ultrafast EBT body scanner, l'EBT étant supérieure au spiral CT scanner à cause de sa dose très faible de radiations, tel que pratiqué par nos partenaires :
-"Colorado Heart & Body Imaging", CO, Denver, USA, www.coloradoheart.com,
-"Lifescore", CA, San Diego, USA, www.lifescore.com,
-et le "Monaco Life Check Center", Monaco, www.monacolifecheck.com, l'EBT combinant faibles rayonnements, rapidité très élevée, haute résolution permettant d'obtenir des clichés uniques de tête, cou, poitrine et abdomen;
2) et examen sanguin : cancer check-up Cancersafe®test.

Attention :

« que conclure si mes marqueurs tumoraux sont négatifs ? »
Bien sûr, c’est une bonne nouvelle, mais il faut toujours rester vigilant. Cela ne signifie pas de façon absolue qu’il n’y a pas cancer. Le test doit être renouvelé régulièrement.

« que conclure si mes marqueurs tumoraux (1 ou plusieurs) sont positifs ? »
Cela ne signifie pas obligatoirement qu’il y a cancer (le commentaire accompagnant vos résultats donnera des explications). La visite chez votre médecin est hautement recommandée, il entreprendra les investigations nécessaires à l’établissement d’un diagnostic éventuel. Il faut bien comprendre que le problème de mettre au jour de nouveaux cas de cancers et de se heurter à de "faux-positifs" est typique des nouvelles technologies, ce qui ne doit pas conduire à se priver de leur utilisation. Ce risque est diminué chez Cancersafe, gràce à l'emploi de ses algorithmes spécialement développés pour délivrer une opinion plus sûre.

Pour conclure, en matière de prévention, il existe :
- chez la femme : mammographie, échographie, frottis cervical, radiographies, colonoscopie, scanners, IRM ;
- chez l’homme : PSA, échographie, radiographies, colonoscopie, scanners, IRM.
Ces examens sont généralement invasifs (rayons X, biopsies) :
un examen sanguin ne l’est pas : seule une prise de sang est nécessaire.
Cancersafe®test est le SEUL EXAMEN COMPLET de marqueurs tumoraux, rendu avec l’expertise de spécialistes reconnus.


CANCER AND TUMOR MARKERS

By J.Chaumont, PhD, ECC, clinical biochemist, oncobiologist counsellor for Cancersafe.
D.Serin, MD, ASCO-ASTRO corresponding member, oncologist counsellor for Cancersafe.


To celebrate the availability in the US of a new complete cancer test, the Cancersafe®test from Switzerland, using a tumor marker panel, here is a statement about cancer and one of its many aspects : the tumor markers, a great help in monitoring this threat for everybody.

How can I take control in cancer field?

Cancer is the No. 1 killer, because, often, treatment occurs late : after the diagnosis is made.
And diagnosis is made after clinical signs are noticed, by you yourself : you feel a lump in your breast, you observe an unusual bleeding…So, with your symptoms you see your doctor who prescribes tests : to improve noticeably the treatments results, large progress has to be undertaken sooner : here we come to prevention and early detection :
Prevention depends, firstly, in your behaviour : everybody knows today that reducing tobacco and alcohol consumption would eliminate 50% of all cancers!
Prevention is, secondly, in performing tests : some are invasive (X-rays) : mammography for women, colonoscopy; or non-invasive : PapSmear for women, now MRI; and check-ups with blood drawing : the best known is PSA dosage for men and prostate cancer.
When such tests lead to a positive result, other investigations will differentiate between “real cancer” or “false positive result” : as we have no clinical sign, in the case of real cancer, we speak of “early detection” : obviously, the treatment will have a better chance to heal the patient, since it would begin months or even years before the clinical signs would have occurred.
The same early detection is interesting in cancer “follow-up” : depending upon the type of cancer, metastasis will occur sooner or later : for instance, breast cancer spreads out very early. It’s then absolutely necessary to follow the patients after their treatment. In the case of women having suffered from breast cancer, they have to be followed for their whole life : in this case, relapse remains a permanent threat.
It is advisable to try to detect the presence of a cancer, or a relapse, as soon as possible. Based on scientific research and expert opinion, there are recommendations (ACS, NCI, and many others) to detect cancer early in asymptomatic people (people without symptoms of cancer), and in treated people, to make sure they are definitely healed :
The earlier cancer is diagnosed, the more likely the chance for long-term survival.
As described above (mammography, colonoscopy, now scanners and MRI, Papsmear), there are in fact very few tests. Using the tumor markers, not only isolated ones as PSA, but in a large combination of them, can help to noticeably improve the cancer prevention, and relapse prevention.

What are Tumor Markers?

Tumor markers are substances found in the blood stream, urine, or tissues from some patients developing some types of tumors. These markers are products from – either the tumor itself,- or the body, in response to the real presence of cancer or only of benign conditions : here lies the difficulty in managing the tumor markers.
These markers are proteins, or enzymes, or hormones, or antigens. Some are very specific : that means they are produced quite exclusively by a special tumor; conversely, other ones are produced as well by normal cells as by cancerous cells, the result being that these markers are much less specific.
Ideally, a good tumor marker needs to :
-be specific of one pathology;
-be sensitive : its cut-off is low;
-deliver a value correlated to the tumor mass;
-have a short life duration, in order to enable an efficient follow-up : decreasing during treatment, increasing before a relapse.
The tumor markers are then useful, depending upon the cancers, for detection, or follow-up.

Available at presently on the market there exists a special test, developed by a Swiss company : the Cancersafe® test, from Cancersafe SA, Switzerland.
This test uses an original concept : perform a 10 (for women) and 11 (for men) tumor markers panel, in order to deliver, thanks to special expertise, the opinion of four doctors, trained since years in cancer monitoring.


Here follows a succinct description of the TMs used, from the “classical” ones (such as the PSA or CEA), to the up-to-date ones, not yet used in the US (such as the CA 72-4 or the Cyfra 21-1).

CEA : it’s the oldest TM used : with no specificity, it remains largely used because, covering a large range of pathologies, it allows following several different cancers. It was primarily used in colorectal cancer monitoring. In colon cancer and rectum cancer, the CEA level is closely related to the tumoral differentiation and carcinoma stage.
Significant increase is observed in relapses, preceding clinical signs from 2 to 12 months.
Apart from the digestive area, CEA is used in particular in lung cancer, thyroid cancer, and also ovary, liver, uterine.
Preferably it should be used with other TMs, such as CA 15-3, CA 19-9, CA 125, CA 72-4, NSE, Cyfra 21, depending upon the considered cancer.
CA 15-3 : glycoprotein, circulating antigen associated to human mammary tumors.
Commonly called “breast cancer marker”, it’s generally coupled to CEA in breast cancer monitoring.
Its level is moderately elevated in 30 to 50% of patients when breast cancer diagnostic is found, this percentage varying with the tumor’s size. There is no correlation with histological grade.
In follow-up, CA 15-3 is elevated in 90% (cases) of first metastasis discovery : levels higher than 100 UI/ml are almost exclusively associated with metastases.
In silent metastatic breast cancer, CA 15-3 is elevated in 56% of the cases, CEA in 53% of the cases, but one of them (when simultaneously used) is increased in 81% of the cases : in 2 cases out of 3, an increase in one of them is observed long before the secondary localisation appears.
The couple CEA-CA 15-3 is the first example of using several TMs rather than an isolated one : its observation has lead us to a much larger concept : monitoring a panel of TMs, in order to cover more efficiently a wide range of cancers.
To illustrate this concept, be aware that, at present, in the most advanced laboratories (in Europe and Japan, not in the US!), we use to test CA 15-3+CEA coupled with the Cyfra 21-1, this last one being the best, by far, to detect metastasis (see below).
CA 19-9 : initially discovered among patients suffering from colorectal cancer, CA 19-9 was then noticed in pancreas cancer (very high levels), biliary tract cancers, stomach cancer.
Watch out for very high levels found in inflammatory diseases of the gastrointestinal tract, or biliary retention : when inflammation is treated, or the obstacle relieved, the CA 19-9 level normalizes very fast.
CA 125 : very interesting marker for ovarian cancer : the CA 125 is the essential marker for this cancer. It’s THE marker in serous adenocarcinomas. The cut-off at 35 UI/l allows distinguishing women free of cancer from patients suffering this cancer, with a specificity between 82-100%.
In mucinous carcinomas, it has to be associated with CEA and CA 19-9.
In germinal tumors, we associate it with AFP and BHCG (see below).
CA 125 is also used in lung cancer : in the “small cells” form, it’s used with the NSE (see below).
CA 72-4 : diagnosing gastric carcinoma is often complicated and can be extremely difficult due to presentation with vague, non-specific symptoms that are sometimes associated with non-malignant disease.
Although endoscopy, coupled with histologic evaluation of biopsy specimens, is most often used to make definitive diagnosis, the search for additional non-invasive diagnostic procedures has longed continued : strong new clinical evidence has recently emphasized the clinical value of the CA 72-4 serum tumor marker assay in diagnosis and monitoring of gastric cancer : CA 72-4 is THE stomach cancer tumor marker.
We use it, to be largely complete, with CEA and CA 19-9.
AFP : the developing foetus normally produces the alphafoetoprotein. Its level decreases fast after birth, and normally is not detectable in safe adult’s blood (except during pregnancy). Elevated results of the AFP strongly suggest the presence of primitive liver cancer, or a germinal ovarian or testicular cancer.
The AFP’s interest lies in cancers of : liver, then ovary and testicle.
BHCG : the HCG is normally produced by placenta during pregnancy : in fact, it’s used as pregnancy test, since its level grows fast in first three months.
Apart from this field, BHCG is used for testicular cancer, where high levels can be observed; less commonly, ovary, liver, and last, stomach, pancreas and lung.
Be aware that marijuana consumption leads to increased levels.
PSA : a very good marker, very well known, because of its high specificity : found in normal prostatic epithelioma and secretions, but not in other tissues. It’s a glycoprotein, whose function is to liquefy the seminal plasma.
PSA is normally present, in low concentrations, in every male adult’s blood. Produced by normal and abnormal cells of the prostate, it is highly sensitive to the presence of prostate cancer : its increasing is correlated to the tumor grade and its volume.
The PSA, as a sensitive test, is used for screening for all men over 50. Decreased mortality from the disease could be between 20 to 30%.
As an ultra sensitive PSA is available, enabling to track 0,001 ng/ml, we can find every elevation of the value, after treatment. When serious follow-up is needed, we can discriminate : early increases mean a metastatic disease evolution, while late increases rather mean local relapse.
But there does exist a major benign condition of PSA increasing : inflammation or trauma of the prostate, benign hypertrophy of the prostate are frequently involved : to clear the matter, without invasive biopsy, the FPSA/PSA ratio level is now available.
FPSA : very often, it’s interesting to couple the freePSA with the PSA. The known “PSA” (for prostate specific antigen) is, in fact, blood circulating under 2 forms : a free one, the FPSA, and an attached one (to alpha1antitrypsin); the FPSA represents 10 to 40% of the PSA (total PSA).
Patients with a prostate cancer show a FPSA/TPSA ratio lower than people with benign hypertrophy : when ratio is lower than 0.25, be careful : there is risk of cancer; the lower the ratio, higher the risk. When the range is between 0 to 0,25, it covers 95% of cancers.
Using the PSA and FPSA dosages significantly reduces the number of unnecessary biopsies.
B2M : the “beta2microglobulin” is used as tumor marker in different diseases of the haematopoietic system, essentially when lymphoid B cells are involved : leukemias, myelomas.
NSE : the NSE (neuroenzym-specific-enolase) is an enzyme only found is nervous tissue or in neuroendocrine tissue. At present, it is used first in lung cancer, the “small cells” one. There exists a correlation between the scattering of the small cells cancer and the NSE level : in limited forms, 50% show high levels; in disseminated cancers, 100% show high levels.
Besides its interest in diagnostics, the NSE, during the first sessions of chemotherapy (when required), allows the appreciation of the quality of the response to the treatment : its level increases during the cells lyse, thus demonstrating the tumor’s sensitivity to the treatment.
Moreover, the NSE shows high levels in neuroblastomas, pheochromocytomas, and is also used in medullar thyroid cancer.
CYFRA 21-1 : the “cytokeratin fragment” is the most stunning marker ever discovered. Very few labs monitor it at present. It is specially interesting for lung cancer, diagnostic and follow-up of epidermoidis forms.
Among all forms of lung cancer (lung cancer presents many different forms), the Cyfra 21-1 delivers an appreciated sensitivity of 65%, and an exceptional specificity of 95%. Its value is closely tied to the stage : levels increase progressively from limited stages to disseminated ones.
While surgery has long been the unique solution for these cancers (“non small cells” ones), the association radiotherapy-chemotherapy, even for locally advanced stages, is used at present : the regular evaluation of the Cyfra allows easier follow-up treatment, and even better when associated with other TMs (see below).
As described above (CA 15-3), the Cyfra is now used by top teams in breast cancer : its elevation in follow-up demonstrates, very early, the apparition of metastases.
Cyfra can also be used in uterine cancer, oesophagus cancer, bladder cancer.

The pathologies and theit tumor markers

 Breast CA15-3, CEA, Cyfra 21-1.
 Ovary CEA, CA125, CA 19-9; AFP, BHCG.
 Uterine SCC, Cyfra 21-1 ; CEA, CA 19-9, CA 125.
 Prostate PSA, FPSA and ratio.
 Testicle BHCG, AFP.
 Colorectal CEA, CA 19-9, CA 125.
 Pancreas CEA, CA 19-9, CA 72-4.
 Liver AFP, CEA.
 Stomach CA 72-4, CEA, CA 19-9.
 Oesophagus CEA, Cyfra 21-1.
 Thyroid CEA, NSE.
 Lung NSE, CYFRA 21-1; CEA, CA 125, CA 19-9.
 Bladder TPA, CEA, Cyfra 21-1.

Values of tumor markers : range, moderate to high values

 CEA ng/ml <5 5-10 10->100 000
 AFP ng/ml <15 15-200 200-10 000
 PSA ng/ml <4 4-10 10-1 000
 FPSA/PSA ratio : >0.25 . <0.25 <0.10
 CA 15-3 U/ml <40 40-60 60-30 000
 CA 19-9 U/ml <35 35-100 100-5 000 000
 CA 125 U/ml <35 35-50 50- 50 000
 CA 72-4‘ U/ml <6.7 7-30 30-10 000
 BHCG UI/ml <5 >5 5-500 000
 B2M mg/l <2 >2 2-10
 NSE ng/ml <21 22-40 40-10 000
 CYFRA 21 ng/ml <3,5 >3,5 3,5-1000.


WHY USE A PANEL OF TUMOR MARKERS?

In prevention : the broader the spectrum, the larger the chances to find out a cancer. The reasoning is similar to using antibiotics associations in some antibiotherapies. Of course, it’s not a guarantee. There are 2 main objections frequently met :
1) “I got all negative results, nevertheless I was diagnosed 6 months later!!!”. This is the case of “false negative results”. Of course, there are limits to the method, as always. It depends upon the cut-offs chosen : if the values are set too low, more cancers will be detected, but there will be too many “false-positive” tests, meaning high results due to benign conditions; if values are set too high, less cancers will be found out, but lot of “false negatives” will occur. The judicious choice of the range values relies on the expertise of the doctors signing the reports.
A negative result never means you’ve not got cancer, it means you have no detectable cancer, with biology, at this moment : it’s good news, not absolute news. It means also you have to perform the test regularly, say once a year : thus, you’ll build your own data that will be of the utmost importance should cancer occur later in your life. And it will :
for about 1 person of 3!!! Ladies, don’t forget that 1 woman of 9 will develop a breast cancer in her life…
2) “I got a positive result, I was firmly advised to perform complete exploration to clear the matter, and finally I am cancer-free!!!”. Happy you are! This is the case of “false positive results”. The importance of positive results, one or several, the heights of these results, lead to special, personal comments from our trained team. We’ll always firmly ask you to meet your Doctor : further evaluations will lead to complete explanation : cancer or not cancer.
Remain realistic : using such a panel will never allow finding out all latent cancers. It’s aimed to detect some of them, enabling to start treatment in advance, boosting the chances to heal. And perform it regularly.

In follow-up : the use in follow-up is largely achieved. The goal is to monitor treatments, to search later any relapse (before clinical signs if possible!).
An original example of the interest of several TMs used together is demonstrated in lung cancer : always remember the heterogeneousness of the broncho-pulmonary cancers : several histologically distinct clones can coexist in a same tumor :
considering a “small cells” cancer (SCLC), where the NSE is initially high and Cyfra normal, an efficient chemotherapy on small cells clones can select the “non small cells” clones, explaining the relapse while the NSE is lowering : you have the explanation, when performing the Cyfra : it increases. And the treatment has to be changed…
In lung cancer, always perform CEA, CA 125, NSE and Cyfra 21!
And concerning this lung cancer, please note an interesting fact : only (if only!) one smoker of 8 will develop a lung cancer. Nobody knows, at present, why only one, and not the 8. So, it is in the interest of all those persons who keep smoking to check regularly.

Why the "Cancersafe® test"?
In order to cover a large range of cancers ( the main ones ), the "Cancersafe® test" incorporates the main tumor markers that are available the world over. Thanks to expert utilization ( materials and methods from Roche-Boehringer and Abbott laboratories ), this test can look for : breast, ovarian, lung, uterine, prostate, testicle, colorectal, pancreas, liver, stomach, thyroid.
Who would perform the test?
Everybody, especially over 50. And young women, caring about breast and ovary. And perform once a year, building your baseline and data for future :
Years passing, your report will build graphs, demonstrating the evolution of every one of the 10 (or 11) TMs.

The panel for women : CEA, CA 15-3, CA 19-9, CA 125, CA 72-4, AFP, BHCG, B2M, NSE, CYFRA 21-1.

The panel for men : CEA, CA 19-9, CA 125, CA 72-4, PSA+FPSA, AFP, BHCG, B2M, NSE, CYFRA 21-1.

It is fast, affordable, convenient, non-invasive. and exclusive.
-Fast : your report is delivered, with comments, only one hour after your serum spec reached the lab facility.
-Affordable : priced at only $800, due to volumes and experience of the specialized labs, it’s not expensive : in the US, such a panel would be priced (without CA 72-4 and Cyfra) at $1000 or more, and without our team’s expertise.
-Convenient : easy to get : just a blood sampling.
-Non-invasive : no X-rays wanted, only draw the blood from your arm.
-Exclusive : nobody else, the world over, offers such a sophisticated test (technology and expertise).

And renew regularly (once/year or more if necessary).

Copyright 2005, all reproduction without Cancersafe authorization strictly prohibited.


L'information présentée sur le site Cancersafe est destinée à conforter, et non remplacer, la relation qui existe entre nos visiteurs et leurs médecins.




Cancersafe® vient d'ouvrir son nouveau site, www.smokertest.com, à l'intention des fumeurs.

Cancersafe®test : Earth's biggest test for cancer detection.


 

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