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Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
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Gastrointestinal Tumour Markers

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This is a presentation at Apollo Hospital Kolkata, where Dr nagarjun Rao was my mentor and guide

This is a presentation at Apollo Hospital Kolkata, where Dr nagarjun Rao was my mentor and guide

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  • 1. Gastrointestinal tumor markers Nagarjun Rao MD, FRCPath, Diplomate of American Board of Pathology Ratnadeep Ganguly MD Apollo Gleneagles Hospitals Kolkata
  • 2. Introduction
    • Tumor markers - Measurable molecules that are associated with a malignancy.
    • Tumor-derived - produced by tumor cells OR
    • Tumor-associated – produced by the body in response to tumor.
    • May be in circulation or tissue bound.
    • Although there are a multitude of tumor markers, very few of them have found their way into clinical practice because of their lack of specificity. However, some of these non-specific markers have found a place in monitoring cancer treatment rather than in diagnosis.
  • 3. Introduction (contd.)
    • Clinical uses –
      • Diagnosis
      • Staging
      • To indicate prognosis
      • To monitor treatment
      • In follow-up to monitor for cancer recurrence.
  • 4. Diagnosis
    • Some tumor markers are associated with many types of cancer; others, with as few as one – Not specific
    • Some tumor markers are always elevated in specific cancers; most are less predictable.
    • Most are found in low levels in healthy persons,
    • Can be associated with non-neoplastic diseases as well.
    • No tumor marker test is free of false negatives or false positives.
  • 5. Staging and prognosis
    • Quantitative assays can be useful for staging - higher levels can indicate more advanced cancer and a worse prognosis in some cases.
    • This info can be used in choosing treatment modalities
  • 6. Treatment monitoring
    • The most common use of tumor markers.
    • Levels drop with response to Rx.
    • Stable or increasing levels often indicate lack of response.
    • The choice of tumor marker to use for monitoring is important.
      • Use only a marker elevated before treatment.
      • Timing of the tests – Enough time must be given for initial marker to be completely cleared from the blood. False elevations may be seen with tests done too soon.
  • 7. Recurrence
    • Periodic testing can detect a recurrence earlier than an ultrasound, x ray, or physical examination.
  • 8. Methodology
    • Immunoassay –
      • Antigen (tumor marker) + Antibody -> If that tumor marker is present, these very specific antibodies bind to the markers.
      • Some type of label, often a radioactive substance, is then used to measure the amount of bound marker and antibody -> The quantity of tumor marker is calculated.
  • 9. Colorectal cancer
    • Diagnosis and screening
    • CEA – A glycoprotein which is the most useful and widely investigated marker for colorectal cancer.
    • Both the proportion of patients with elevated levels and the extent of elevation are primarily dependent on disease stage.
    • >2.5 ng/ml - 28% Duke’s A
    • 45% Duke’s B
    • 75% Duke’s C
    • 84% Duke’s D
  • 10. Colorectal cancer
    • > 5 ng/ml – Proportion of patients with increased levels – 3% Duke’s A
      • 25% Duke’s B
    • 45% Duke’s C
    • 65% Duke’s D
    • Lack of sensitivity for early disease - CEA is of little value in the detection of Dukes’ A or B colorectal cancer.
    • Lack of specificity - Only approximately 90% using a cut-off point of 2.5 ng/ml . Benign diseases and other advanced types of adenocarcinoma can cause ↑ CEA.
    • CEA cannot be used as a screening test in asymptomatic populations
    • Cannot be used as a diagnostic marker
    • In a patient with symptoms with a grossly elevated value - Highly suggestive of colorectal ca.
  • 11.  
  • 12. Colorectal cancer
    • Prognosis
    • High levels correspond with more advanced stages
    • Duke’s B – High levels of CEA may help identifying a sub-group who have a higher risk of aggressive disease who may require adjuvant treatment
    • Preliminary data suggest that both serum and tissue levels of CA 19-9 may also be prognostic in colorectal cancer.
  • 13. Colorectal cancer
    • Monitoring
    • Marker of choice for monitoring patients with colorectal cancer – since 1980s
    • Early studies showed that serial CEA levels could detect recurrent disease many months (usually 4-10 months) in advance of clinical evidence of disease
    • Most sensitive for hepatic or retroperitoneal disease; Relatively insensitive for either local, peritoneal or pulmonary involvement.
    • Some investigators - A slowly rising CEA usually indicates a locoregional recurrence while rapidly increasing levels usually suggest hepatic metastasis.
  • 14. Colorectal cancer
    • Monitoring (contd.)
    • Pietra N et al. Dis colon rectum, 1998
    • Single institution prospective randomized trial to appraise the value of CEA in detecting local recurrence.
    • 207 patients; ↑ CEA - most frequent indication of local recurrence in patients without clinical symptoms.
    • CEA measurement was more cost-effective than other procedures including CT for the diagnosis of local recurrence.
    • Intensive follow-up with CEA might be more beneficial for patients with rectal cancer than for those with colonic cancer, as local recurrence was more frequent after rectal cancer resection.
    • Optimal interval for serial CEA screening – 2-3 months
  • 15. Colorectal cancer
    • Other markers –
      • CA19-9, CA242 and cytokeratins ( e.g., TPA and TPS) have also been evaluated for this malignancy . May complement CEA; further work required to see which marker is most complementary to CEA.
  • 16. Pancreatic cancer
    • Diagnosis
    • CA 19-9 – Most widely used
    • Mean specificity – 90%, sensitivity – 81%, using a cut-off point of 37 IU/ml
    • May be raised in other conditions – other advanced cancers, non-neoplastic conditions including pancreatitis, cholangitis and hepatocellular jaundice
    • In presence of jaundice – specificity becomes lesser
    • Of limited value in diagnosing pancreatic cancer, esp. early cases – can complement radiologic procedures, especially in non-jaundiced pts.; only 55% of patients with tumors <3 cm in size have ↑ CA 19-9.
  • 17. Pancreatic cancer
    • Prognosis and monitoring
    • CA 19-9 has the potential but is as yet unproven for routine use for these purposes
    • Other markers such as CA50, CA242, CA195, DU-PAN 2, and CAM 17.1/WGA have also been described for pancreatic cancer.
    • Investigated less widely than CA19-9 but appear to provide similar data.
    • CA19-9 therefore remains the &quot;gold standard marker&quot; against which future markers for pancreatic cancer will be evaluated.
  • 18. Gastric cancer
    • The most widely described markers for gastric cancer are CEA, CA19-9 and CA72-4.
    • Of these CA72-4 appears to be the most sensitive and specific, followed by CA19-9 and CEA.
    • None of these markers is useful in either screening or diagnosing early gastric cancer.
    • Their role in the follow-up of patients with diagnosed disease remains to be evaluated.
  • 19. Esophageal cancer
    • Biochemical markers have been little investigated in esophageal cancer.
    • Preliminary data - best available markers for the squamous cell ca. are SCC and cytokeratins [ e.g ., CYFRA 21-1, TPA, TPS] ; CA19-9 - adenocarcinoma.
    • Presently, these markers are of little value in either the diagnosis or management of oesophageal cancer.
  • 20. Hepatocellular carcinoma
    • Screening
    • α -fetoprotein – marker of choice
    • Value of AFP in screening has not been assessed in a prospective randomized trial.
    • For endemic areas with high prevalence.
    • NIH consensus conference (1986): HBsAg +, with CAH or cirrhosis to be screened every 3 months and every 4-6 months on USG.
  • 21. Hepatocellular carcinoma
    • Diagnosis
    • Differential diagnosis between HCC and hepatitis &/or cirrhosis
    • Measurement of fucosylated fraction of AFP (AFP L3, P4 and P5) versus “normal” AFP – more in HCC.
    • In benign conditions – AFP elevations are transient, in malignancy concs. remain high or may increase – AFP assays at 2-3 weeks’ interval may eliminate false-raised values
  • 22. Conclusions
    • Screening:
      • Lack of sensitivity for early disease and lack of specificity for malignancy
      • The above coupled with low prevalence of GIT cancers in general pop. prevent the use of these markers in screening asymptomatic general pops. Exception : AFP screening in high risk areas.
  • 23. Conclusions
    • Diagnosis
      • Limited due to lack of sensitivity of these markers
    • Follow-up of patients with diagnosed cancers
      • To detect asymptomatic recurrences that can be operated upon for cure
      • Cheaper than conventional radiological procedures
  • 24. Conclusions
    • Caveats while using CEA in surveillance of pts. with diagnosed colorectal cancer :
      • ↑ usually in advanced disease
      • Not all patients with recurrent disease will have ↑ levels
      • High levels may occur in other conditions
      • Some cytotoxic therapies can cause transient rise of levels
  • 25. Conclusions
    • Esophageal and gastric cancer – Markers contribute very little to diagnosis or follow-up
    • Future approaches: Assays for mutated c-oncogenes and suppressor genes

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