2002 Fiscal Year Final Research Report Summary
Clinical Significance for detection of circulating renal cancer cells in the blood by RT-PCR
| Project/Area Number |
12470337
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Nara Medical University |
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Principal Investigator |
HIAO Yoshihiko Dept. Urology, Nara Medical University, Professor, 医学部, 教授 (00133207)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Kazuhiro 2^<nd> Dept. Pathology, Aichi Med. University, Assit. Professor, 医学部, 講師 (60109759)
CHO Masaki Dept. Urology, Nara Medical University, Stuff, 医学部, 助手 (90285362)
UEMURA Hirotsugu Dept. Urology, Nara Medical University, Assit. Professor, 医学部, 講師 (90213397)
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| Project Period (FY) |
2000 – 2002
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| Keywords | renal cell carcinoma / MN / CA9 / antigen peptide / RT-PCR |
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| Research Abstract |
Renal cell carcinoma is considered as a very poor prognostic disease due to absence of specific tumor marker and effective therapeutic modalities. Conventional treatments such as chemotherapy and radiotherapy are not useful at all. We are previously investigating to detect circulating renal cancer cells in the patient's blood and established RT-PCR assay to detect MN/CA9 positive cells in the peripheral blood. The blood-based RT-PCR resulted in detection of MN/CA9 mRNA in 76% of RCC patients. However; detection of MN/CA9 positive cells was observed in 30% of healthy volunteers (false positive). This may be because the skin expresses MN/CA9 antigen and aspiration of MN/CA9 positive cell when taking the blood via skin. Considering this situation, we try to use blood sample from renal vein during radical nephrectomy. To optimize PCR condition, we investigated 96 sets of PCR primers, and were able to set up blood-based RT-PCR with approximately 70 % sensitivity and 90 % specificity. We expected such high detection rates and no correlation with prognostic factors such as stage, grade and metastases, was observed. Based on these findings, we focused on cadherin-6 as an additional targeting molecule. Cadherin-6 is cell-cell adhesional molecule and considered as an as an important biomarker in renal cell carrinomas. We set up blood-based RT-PCR double assay targeting to MN/CA9 and Cadherin-6. Prospective study with blood samples from renal vein during radical nephrectomy revealed that significantly high detection rate of MN/CA9 and/or Cadherin-6 positive cells was observed in RCC patients with metastasis. This finding suggests that our double assay may be useful for diagnosis of RCC as well as early detection of metastasis.
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