UNIVERSITAS AIRLANGGA



Detail Article

Folia Medica Indonesiana

ISSN 0303-7932

Vol. 44 / No. 2 / Published : 2008-04

Order : 3, and page :76 - 81

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Original Article :

Detection of cytokeratin 19 mrna in blood as an early marker of micrometastatic tumor cells of nasopharyngeal carcinoma patients in surabaya

Author :

  1. Harianto Notopuro*1
  2. Widodo A Kentjono*2
  3. Retno Handajani *3
  4. Francisca Notopuro*4
  1. Departement of Biochemistry, Airlangga University School of Medicine and Institute of Tropical Disease
  2. Departement of Ear, Nose and Throat, Airlangga University School of Medicine, Dr Soetomo Teaching Hospital
  3. Departement of Biochemistry, Airlangga University School of Medicine and Institute of Tropical Disease
  4. Departement of Radiology, Airlangga University School of Medicine, and Dr Soetomo Teaching Hospital

Abstract :

Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy triggered by Epstein Barr virus that occurs at a high frequency in certain regions of southeast Asia. Previous studies reported that this tumor was a radiosensitive but the predominant failure after adequate radiotherapy was due to its distant metastasis. It would be of value to detect the presence of metastasis as early as possible. Previous studies have shown that cytokeratin 19 (Ck 19) positive cells indicate the presence of micrometastasis. The purpose of this study was to evaluate the presence of Ck 19 mRNA by nested RT-PCR in established NPC patients and its correlation to the various stages of NPC as determined by conventional clinical examination. The reported sensitivity of RT-PCR was around 1/107, i.e one cancer cell can be detected among 107 normal blood cells. Venous blood samples from 30 patients with biopsy-proven nasopharyngeal carcinoma and 10 ENT non NPC patients were tested. After we isolated total mRNA with Trizol reagent, the procedure was continued with nested RT-PCR. The primer sets were directed to conserved regions of Ck 19 genome encoding cytokeratin protein (outer primers: Ck 19-1 & Ck 19-2 and inner primers: Ck 19-3 & Ck 19-4). A distinct 518 bp band (it cannot be seen on agarose gel electrophoresis) and 371 bp of the PCR products indicated the presence of mRNA Ck 19. Results showed that Ck 19 mRNA was obtained in 22 (73%) of 25 NPC patients with several stages and none of 10 (0%) ENT non NPC patients. We divided 30 NPC patients into 4 groups according to TNM system (WHO criteria): Stage I: none, Stage IIa : 1 patient (Ck 19 mRNA was negative), Stage IIb: 1 patient (Ck 19 mRNA was negative), Stage III: 3 patients from 5 patients had Ck 19 mRNA positive (60%), Stage IVa: 5 patients from 7 had Ck 19 mRNA positive (72%) and Stage IVb: 14 patients from 16 patients had Ck 19 mRNA positive (87,5%). No Ck 19 positive cells were detected in control group, 10 patients ENT non NPC (0%), i.e 100% specificity.  Our data indicated that the positive detection rate for Ck 19 mRNA in peripheral blood increased as the clinical stage of tumor increased, and the correlation was strong with statistical significance of r = 0.95 and t > 0.02. In conclusion, this study shows that the presence of Ck 19 mRNA, as detected by RT-PCR in NPC, is only significantly associated with micrometastasis tumor. It is a highly specific and sensitive method. Ck 19 mRNA detection is a useful and reliable method to monitor local recurrence and tumor metastasis in NPC patients. It helps to detect recurrence and tumor metastasis early and may improve local and systemic control and enhance patient’s survival.

Keyword :

Nasopharyngeal Carcinoma, Ck 19 mRNA , nested RT-PCR , micrometastatic tumor cells,


References :

Hu, LF, Chen, F, Zheng, X, Ernberg, I, Cao, SL, Christensson, B,(1996) Nasopharyngeal Carcinoma and Eipstein-Barr Virus, Microbiology and Tumor Biology Centre Stockholm : Publisher Karolinska Institutet

Bustin, SA, Gyselman, VG, William, NS, Dorudi, S,(1999) Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients - : Br J Cancer

Dingemans, AMC, Brakenhoff, RH, Postmus, PE, Giaccone, G,(1997) Detection of cytokeratin 19 transcripts by reverse transcriptase polymerase chain reaction in lung cancer cell lines and blood of lung cancer patients - : Lab Invest





Archive Article

Cover Media Content

Volume : 44 / No. : 2 / Pub. : 2008-04
  1. Tgf-β1 As The Trigger Of Pulp Fibroblast Proliferation
  2. Difference In Cyclooxygenase-2 (cox-2) Expression Between Low And High Grade Papillary Carcinoma In Human Bladder Cancer
  3. Detection Of Cytokeratin 19 Mrna In Blood As An Early Marker Of Micrometastatic Tumor Cells Of Nasopharyngeal Carcinoma Patients In Surabaya
  4. Pcr Technique Detection Of Chlamydia Trachomatis Dna Band Using Silver Nitrate Staining
  5. Change Of Cd4 Count, Hsp70 And Anti-hsp70 Levels In Hiv Patients
  6. Hiv/aids Prevalence In Surabaya, Indonesia
  7. Treatment Response And Acute Toxicity Evaluation Of 70 Gray Radiation In Nasopharyngeal Carcinoma Patients In Dr Soetomo Hospital, Surabaya
  8. Pharmacodynamic Effects Of Ligustroside Glycoside (a Cns Active Substance) Isolated From Fraxinus Graffithii Clarke Against Chemically Induced Seizures On Mice
  9. Management Of Acute Glomerulonephritis In A Child With Ischemic Stroke And Hypertensive Crisis
  10. Efficacy Of Orlistat Plus Diet Compared To Diet Alone In Reducing Body Weight And Body Mass Index
  11. Review Article: Pathogenesis Of Repeated Abortion In Polycystic Ovarian Syndrome (pcos)
  12. Review Article: Protein Calorie Malnutrition And Immune Response In Children
  13. Review Article And Clinical Experience: Varenicline (champix®) : A Breakthrough For Smoking Cessation Treatment (an α4ß2 Nicotinic Acethylcholine Receptor Partial Agonist)

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