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PubMedDate not supplied

Immunocytochemical detection of circulating esophageal carcinoma cells by immunomagnetic separation.

BACKGROUND: Recent developments in detection of micrometastasis have revealed a considerable incidence of systemic disease in patients who would previously have been diagnosed as having solid tumours only. The purpose of this study was to investigate the prevalence and clinical significance of circulating carcinoma cells in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Peripheral blood samples from 47 primary ESCC patients were enriched by immunomagnetic separation (IMS) using Ber-EP4-conjugated beads (Dynabeads anti-epithelial cell) and immunostained with an anti-cytokeratin (anti-CK) antibody. We assayed samples from 12 patients to compare the detection of CK-reactive cells using IMS with the detection of CK 19 mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) method. RESULTS: CK-reactive cells were observed in 18 out of 47 patients (38%). The detection rate was closely correlated with the stage of disease (TNM stage) (p = 0.0017). In 33 patients who underwent esophagectomy, 4 out of 7 patients (57%) positive for CK cells and only 2 out of 26 patients (7.7%) negative suffered from recurrence in the distant lymph nodes or lungs (p = 0.0108). When IMS and RT-PCR were compared, all 3 samples that were CK-positive by IMS had CK 19 mRNA detected by RT-PCR. However, the other 4 samples with CK 19 mRNA by RT-PCR were negative for CK cells by IMS. Of 7 patients positive for CK-reactive cells before chemotherapy or chemoradiotherapy, 4 patients negative after treatment survived but 3 patients who remained positive died within 6 months. CONCLUSION: Immunocytochemical detection of circulating carcinoma cells by IMS may be a specific method for the diagnosis of systemic disease and for monitoring treatment response.

Adult↗

PubMedDate not supplied

Detection of circulating cancer cells by nested reverse transcription-polymerase chain reaction of cytokeratin-19 (K19)--possible clinical significance in advanced gastric cancer.

Intermediate filament cytokeratin-19 (K19) protein is expressed in normal and malignant gastrointestinal epithelial cells, but not in peripheral blood (PB). Small amount of circulating gastric cancer cells can be detected by a sensitive nested reverse transcription-polymerase chain reaction (RTPCR) with primers specific for K19 mRNA. Thirty-four PB samples obtained from patients with inoperable/metastatic gastric cancer were examined. The mononuclear cell (MNC) fraction was collected by Ficoll centrifugation, and followed by total RNA extraction by acid guanidinium thiocyanate-phenol-chloroform method. RNA from 8 gastric cancer cell lines and the mononuclear cells of 33 healthy adults were used as positive and negative controls, respectively. DNA fragment of 774 bp amplified by the internal primers was found to be a highly reliable marker for K19 mRNA expression. The sensitivity of detection was between 1 and 10 cells/10(6) normal MNCs. The K19 transcripts were detected in 20.6% (7/34; 8-37%, 95% C.I.) of PB samples. None of the other pertinent clinicopathological features, including the disease extent and the histopathologic types of the tumors, were related to the expression of K19 in PB. All 34 patients had been treated by systemic chemotherapy. Among the 17 non-responders to chemotherapy, the survival of the 4 patients with detectable K19 was significantly shorter than that of 13 patients without detectable K19 in their circulating blood (p = 0.014). However, the survival impact of K19 was less significant in the other 17 patients whose tumors had responded to systemic chemotherapy. Of the whole group of patients, the median survival of the 7 and 27 patients with and without detectable K19 in their circulating blood was 1 and 3.5 months, respectively (p = 0.368). We concluded that detecting circulating cancer cells by K19 nested RT-PCR is associated with poor prognosis of gastric cancer, particularly in those patients who are not responsive to systemic chemotherapy.

Adult↗

PubMed2002

High false-positive rate of cytokeratin-19 in detecting circulating tumor cells for nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) harbors a higher metastatic potential than other head and neck cancers. In order to seek a possible surrogate marker for early detection of recurrent or metastatic disease, we tested the feasibility of cytokeratin-19 (CK-19)-nested reverse-transcription polymerase chain reaction (RT-PCR) for detecting circulating tumor cells in NPC patients. METHODS: Two tubes of blood were sequentially collected in individual draws from 7 NPC patients and 15 healthy persons. Total ribonucleic acid (RNA) was extracted from blood cells and treated with deoxyribonuclease. The RNA was then subjected to RT and nested PCR with specific CK-19 primers. The reaction products were run on an agarose gel and visualized under UV light. The sequences of the products were determined using an ABI377 automatic sequencer. RESULTS: Among the 7 NPC cases, 4 cases presented CK- 19 expression with 2 in both tubes, 1 in the first tube, and 1 in the second tube. In the control group, 8 of 15 cases also presented CK-19 expression with 6 in both tubes and 2 in the second tube resulting in a 53.3% false-positive rate. Incidentally, an aberrant splicing product lacking exon 4 of CK-19 messenger RNA was discovered. CONCLUSION: Results of the present study indicate that the CK-19-nested RT-PCR is not suitable for detecting circulating tumor cells in NPC patients because of a high false-positive rate in the control group. The reason for the high rate of false-positives may be attributed to pseudogenes, different blood cell separation methods, or illegitimate expression of CK-19 in blood cells.

False Positive Reactions↗

PubMed1998

[In vitro detection of prostate cancer circulating cells by immunocytochemistry, flow cytometry and RT-PCR PSA].

OBJECTIVE: To evaluate 3 in vitro methods detection (immunocytochemistry, flow cytometry and RT-PCR PSA) of circulating prostate cancer cells from a model of uncap dilution in immortalised lymphocytes. METHODS: In vitro comparison of 3 techniques (immunocytochemistry, flow cytometry, RT-PCR PSA) was performed from a range of dilutions of LbCap cells in immortalised human lymphocytes (concentration range: 1 LnCap cell per 100 lymphocytes to 1 LnCap cell per 100 million lymphocytes). Cells were detected by anti-PSA (prostate specific antigen) and PAP (prostatic acid phosphatase) antibody by immunochemistry, by fluorescent linked antipancytokeratin antibody by flow cytometry and RT-PCR PSA. RESULTS: The limit of detection was 1 LnCap cell per 200,000 lymphocytes (1/2.10(5)) for immunochemistry, 1 LnCap cell per 1,000 lymphocytes (1/1.10(3)) for flow cytometry and 1 LnCap cell per 10 million lymphocytes (1/10(7)) for RT-PCR PSA. CONCLUSION: RT-PCR, due to its most perceptible limit of detection, appears to be the method of choice for the detection of prostatic epithelial cells. Immunocytochemistry has the advantage of providing a quantitative approach. Flow cytometry is limited by the limit of detection of the apparatus used. The prognostic significance of detection of circulating prostate cancer cells remains to be clarified, but the detection of these cells and their correlation with the primary tumour will provide a better understanding of metastatic phenomena.

Acid Phosphatase↗

PubMed2001

Transduction of KAI1/CD82 cDNA promotes hematogenous spread of human lung-cancer cells in natural killer cell-depleted SCID mice.

KAI1, which is identical to CD82, was initially identified as a metastasis-suppressor gene for human prostate cancer, and its expression is reported to be a favorable prognostic factor for operable human lung cancer. In this study, we examined the functional role of KAI1/CD82 in the late phase of metastatic spread of human lung-cancer cells. For this, KAI1/CD82 cDNA was introduced into KAI1/CD82 low-expressing human lung-cancer cell lines, SBC-3 and PC-14, and then the metastatic potential of the transformants was analyzed by i.v. inoculation of KAI1/CD82-transduced cells, SBC-3/KAI1 and PC-14/KAI1, into NK cell-depleted SCID mice. Contrary to our expectations, KAI1/CD82 gene transfer promoted multiorgan metastasis of i.v.-inoculated human lung-cancer cells, while s.c. tumor growth was unaffected. Cancer cells from metastatic tumors of NK cell-depleted SCID mice injected i.v. with SBC-3/KAI1 expressed appreciable cell-surface KAI1/CD82, and cells not expressing KAI1/CD82 (revertants) were not detected in the tumors. Our findings indicate that under conditions where the host's natural cytotoxicity is suppressed, KAI1/CD82 may enhance the formation of tumors by circulating lung-cancer cells at metastatic sites.

Animals↗

PubMed1997

Clinical relevance of bcl-2(MBR)/J(H) rearrangement detected by polymerase chain reaction in the peripheral blood of patients with follicular lymphoma.

We evaluated the prognostic role of peripheral blood polymerase chain reaction (PCR) assay for detection of the bcl-2(MBR)/J(H) rearrangement in 59 patients with follicular lymphoma (FL) treated at our centre since 1989. Thirty-five (59%) patients were bcl-2/J(H) positive and 24 (41%) were negative in the peripheral blood at diagnosis. Peripheral blood bcl-2/J(H) rearrangement detection at diagnosis had no relation to overall survival (OS) and time to progression (TTP). Peripheral blood PCR assay was performed post treatment in 17 patients who were bcl-2/J(H) positive at diagnosis. Fourteen of the patients (82%, 95% CI 56-96%) became bcl-2/J(H) negative. Nine of these patients were further analysed during follow-up and, after several months, circulating cells carrying the bcl-2/J(H) rearrangement reappeared in five of the nine patients. Peripheral blood clearance of bcl-2/J(H)-positive cells was correlated with better overall survival (log-rank P < 0.05) but not with TTP. Our data confirmed that bcl-2(MBR)/J(H) rearrangement detection by PCR at diagnosis is not a prognostic factor in follicular lymphoma. In our series, clearance of circulating bcl-2/J(H)-positive cells appeared to correlate with better overall survival. Post-treatment examination of the peripheral blood by PCR may have clinical relevance for prediction of the survival pattern of the patients.

Genes, bcl-2↗

PubMed1999

Prognostic significance of the detection of circulating malignant cells by reverse transcriptase-polymerase chain reaction in long-term clinically disease-free melanoma patients.

The purpose of this study was to assess the prognostic significance of the detection of circulating melanoma cells by reverse transcriptase-PCR in long-term clinically disease-free melanoma patients. Patients with melanoma who were free of clinical relapse for at least 6 months after primary tumor diagnosis were included and prospectively followed. Tyrosinase mRNA in peripheral blood from these patients was assayed by reverse transcriptase-PCR at the time of their inclusion in the study. One hundred six blood samples from 57 melanoma patients were analyzed. The median time between melanoma diagnosis and inclusion in the study was 24 months (range, 7-51 months). The median follow-up time calculated from the time of inclusion in the study was 27 months (range, 11-36 months). Tyrosinase mRNA in blood was detected in 10 (17.5%) of 57 patients: 2 (18%) of 11 stage I patients, 6 (19%) of 33 stage II patients, and 2 (15%) of 13 stage III patients. Actuarial 2-year DFS was 89% for the tyrosinase-negative patients versus 30% for the positive patients (P = 0.003). Actuarial 2-year OS was 97% for the tyrosinase-negative patients versus 72% for the positive patients (P = 0.001). Tyrosinase mRNA could be detected in the blood of a proportion of long-term disease-free melanoma patients, regardless of their initial clinical stage. The presence of late circulating melanoma cells in this selected group of clinically disease-free patients was significantly associated with a subsequent high risk of relapse and death.

Adult↗

PubMed1999

Hepatic metastasis of gastroenterological cancer: its tumor biology and oncological surgery.

Tumor angiogenesis and ability of basement membrane invasion for invasion of cancer cells into the tumor vessels and for circulating in the blood stream for hepatic metastasis are required. The molecular detection of cancer cells in the circulatory system strongly indicates the possibility of hepatic metastasis of a gastroenterological cancer. As an effect of the general anesthesia or the surgical procedure, a large amount of cancer cells in the tumor vessels may easily enter into the circulatory system at once from the primary tumor beds. Oncological surgeons should understand that the operation is not only the best treatment for gastroenterological cancer but also the crucial event of hepatic metastasis for cancer cells. Although further investigations are required to determine the relationship between circulating cancer cells and hepatic metastasis, at present, the most important issue to be addressed is the development of new strategies for the prevention of hepatic metastasis following the tumor resection in gastroenterological cancer.

Basement Membrane↗

PubMedDate not supplied

Migrating and circulating breast carcinoma cells are within active phases of the cell cycle.

The emergence of blood-borne epithelial-derived tumour cells in breast cancer patients is generally supposed to be an indicator of cancer cell spread but only a very small percentage of these cells ultimately initiate metastases. In this study, we investigated the presence of the cell cycle marker Ki-67 in mammary tumour cells isolated from patients' blood and SKBR3 breast carcinoma cells by confocal laser scanning microscopy. We also compared the immunostaining patterns for Ki-67 of blood-borne tumour cells from the patients with actively migrating cells within a collagen matrix. Both circulating tumour cells and migrating SKBR3 cells were found to be in G1- or S-phase. These findings will have impact on adjuvant chemotherapy as circulating tumour cells that are within the active part of the cell cycle are highly susceptible to chemotherapeutic agents and therefore can be killed while they migrate to distant organs to build a metastasis.

Breast Neoplasms↗

PubMed2003

Detection of circulating cancer cells in human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) cells can invade adjacent tissues and the vascular system at an early stage of tumor progression. In the present study, we have attempted to detect circulating cancer cells. We used human OSCC cells expressing green fluorescent protein (GFP) in an orthotopic nude mouse model and were able to detect GFP-expressing cells using a fluorescence activated cell sorter and fluorescence microscopy. We also detected the expression of GFP, squamous cell carcinoma antigen (SCCA), or epidermal growth factor receptor (EGFR) mRNA in the blood of tumor-bearing mice by conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (TaqMan RT-PCR). TaqMan RT-PCR was the more sensitive method to detect the circulating cancer cells. Furthermore, we examined the expression of SCCA and EGFR mRNA in the peripheral blood of patients with OSCC by conventional RT-PCR and TaqMan RT-PCR. We detected SCCA and EGFR mRNA in few cases by conventional RT-PCR, whereas TaqMan RT-PCR showed their expression in about 50% of cases. However, there was no correlation between detection of circulating viable cancer cells and metastasis to lymph nodes and distant organs. These results suggest that TaqMan RT-PCR is a very useful method and both SCCA and EGFR mRNA may be available as a marker for detection of circulating cancer cells.

Animals↗

PubMed1987

Effects of neutrophil-mediated pulmonary endothelial injury on the localization and metastasis of circulating Walker carcinosarcoma cells.

The lung, a frequent site of cancer metastases, is also a susceptible target in several models of endothelial injury. In previous studies we have demonstrated that such injury, induced by bleomycin or by exposure to high concentrations of atmospheric oxygen, can facilitate the localization and metastasis of circulating tumor cells. Here we have tested the hypothesis that neutrophil-mediated injury to pulmonary endothelium has a similar effect. In Sprague-Dawley rats, intravenous injection of cobra venom factor resulted in complement activation, rapid sequestration of neutrophils in the lung, and endothelial damage, demonstrated by morphology, and by increased protein content and leakage of intravenous 125I-albumin into bronchoalveolar lavage fluids. When 125I-iododeoxyuridine-labeled Walker carcinosarcoma cells were injected intravenously during the period of endothelial injury, the pulmonary capillaries contained aggregates of neutrophils and tumor cells 2 h later, and there was a 3-fold increase in pulmonary tumor cell localization after 24 h in treated animals, compared to controls. Enhancement of tumor cell localization was prevented by pretreatment of the rats with catalase or by antineutrophil antisera. When animals were examined 2 weeks after cell injection, treatment groups had significantly more metastatic tumor nodules and a greater area of lung tissue involved by metastatic tumors. We conclude that neutrophil-mediated damage to the pulmonary endothelium can significantly increase the trapping of circulating tumor cells, and is likely to be clinically important since the large vascular bed of the lung is susceptible to host-mediated injury.

Animals↗

PubMed2004

Combined use of positive and negative immunomagnetic isolation followed by real-time RT-PCR for detection of the circulating tumor cells in patients with colorectal cancers.

To establish a novel molecular diagnostic method of detecting circulating tumor cells (CTCs) LS174T colon cancer cells were serially diluted with normal blood. Additional peripheral blood samples were collected from 25 patients with colorectal carcinoma. Mononuclear cells (MNCs) were collected, equally divided into four parts, and then cancer cells were enriched by four methods: method A, nonimmunobead method; method B, negative immunobead method: CD45 immunomagnetic beads were used to deplete the leukocytes; method C, positive immunobead method: Ber-EP4 immunomagnetic beads were used to enrich cancer cells; method D, negative-and-positive immunobead method: CD45 immunomagnetic beads were first used to deplete the leukocytes from MNC and then Ber-EP4 immunomagnetic beads were used to enrich cancer cells. Finally, real-time quantitative RT-PCR was used to monitor mRNA expression of beta2-mircoglobulin (beta2M) and carcinoembryonic antigen (CEA). The relative CEA mRNA values were corrected with reference to beta2M mRNA, to CEA mRNA/beta2M mRNA ratios according to a CEA mRNA external standards prepared with tenfold serial dilutions (1-10(4) IS174T cells) of cDNA and beta2M mRNA external standards prepared with tenfold serial dilutions (10(2)-10(7) leukocytes) of cDNA. In recovery experiments a significant correlation between the number of cancer cells and CEA mRNA expression was found when CD45 or Ber-EP4 immunomagnetic beads were used alone. A highly significant correlation was found when CD45 and Ber-EP4 immunomagnetic beads were used successively. The sensitivity of method D was one cancer cell per milliliter of blood. Circulating cancer cells were detected in 19 of 25 patients with colorectal cancers. The relative CEA mRNA value obtained by method D was the smallest. The positive detection rate of circulating cancer cells in patients at Dukes' B, C, and D stages were 25.0% (1/4), 83.3% (10/12), and 88.9% (8/9). Combinative use of immunomagnetic isolation followed by real-time RT-PCR is a useful technique to detect circulating tumor cells in patients with colorectal carcinomas. Applying negative and positive immunomagnetic beads successively yields the highest correlation with amount of tumor cells.

Aged↗

PubMed2001

Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status.

OBJECTIVES: To investigate the diurnal variations in circulating tumor cells (CTCs) in metastatic carcinoma of the prostate (CAP) and to determine whether the change in CTCs correlated with disease progression. METHODS: Samples were prepared by immunomagnetic selection of cells from 7 mL of blood targeting the epithelial cell adhesion molecule and differential fluorescent labeling of the collected cells using a nucleic acid dye, antibodies directed against the common leukocyte (CD45), and cytokeratin antigens. Events that stained with the nucleic acid dye and expressed cytokeratin but lacked CD45 were defined as CTCs by multiparameter flow cytometry. RESULTS: Male controls (n = 22) exhibited 0.8 +/- 1.2 events per 7 mL blood compared with 5.9 +/- 4.7 in 10 samples from patients with localized CAP and 46.6 +/- 65.6 events in 10 samples from patients with metastatic CAP. Diurnal testing of 8 cases demonstrated stable levels of CTCs. Ten patients were serially analyzed during a 6-month period for serum prostate-specific antigen and CTCs. The correlation between the prostate-specific antigen level and CTC number was fair. Slow disease progression was found in 4 patients with low CTC numbers (3.0 +/- 3) but it was significantly higher than the control group (P <0.002). Rapid disease progression occurred in 6 patients who demonstrated high CTC numbers (68.5 +/- 71.9). Two patients received chemotherapy that caused substantial fluctuations in the CTCs with less pronounced changes in the prostate-specific antigen level. CONCLUSIONS: We conclude that the level of CTCs can be quantified in the circulation of patients with metastatic CAP and that the change in CTCs correlates with disease progression with no diurnal variations.

Aged↗

PubMed1991

Renal metastases of choriocarcinoma. A clinicopathological study of 31 cases.

From 1949 through 1978, 31 patients with renal metastasis were diagnosed in a total of 448 cases of choriocarcinoma admitted to our hospital, giving an incidence of 6.9%. Renal metastasis was invariably preceded by pulmonary metastases and usually accompanied by other visceral metastases, indicating that renal metastasis is the result of dissemination of tumor cells secondarily from lung metastasis through the general circulation and should be categorized as arterial metastasis. Pyelogram is useful in the presence of medullary invasion by the tumor. Renal metastatic tumors are very sensitive to chemotherapy. Good response to chemical agents may be due to high drug concentration attained in the kidney tissue during excretion. Since successful treatment of renal metastasis by chemotherapy alone may be obtained, patients can be spared a major operation without jeopardizing the prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Decrease in circulating tumor cells as an early marker of therapy effectiveness.

As melanoma cells are present in the circulation of many patients with this cancer, decreases in their number could provide an early indication of therapy effectiveness. To evaluate this possibility, we examined the effect of treatment with a melanoma vaccine on the number of melanoma cells present in the circulation. PCR was used to detect melanoma cells that expressed the melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91 patients with melanoma. Melanoma cells that expressed one or more of these markers were present more often in advanced disease, i.e. in 80% of patients with advanced stage IV compared to in less than one-third of patients with less advanced disease. We then measured circulating melanoma cells in a subset of 43 of these patients who were treated with a polyvalent, shed antigen, melanoma vaccine. The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100. Immunizations were given intradermally q2-3 weeks x4 and then monthly x3. Prior to vaccine treatment, circulating melanoma cells were detected in 14 (32%) patients. Following 4 and 7 months of vaccine treatment, melanoma cells that expressed any of these markers were present in only nine (21%) and three (7%) of patients, respectively. Thus, vaccine therapy was associated with clearance of melanoma cells from the circulation in 78% of initially positive patients. As the number of these cells declined steadily with increasing length of therapy, it is unlikely that this was due to a random change in their number. Rather it suggests that the decline was a result of the therapy. These observations suggest that the presence of melanoma cells in the circulation is related to the extent of the melanoma, and that their disappearance may provide an early marker of the efficacy of therapy. However, the practical utility of assaying circulating tumor cells as a guide to the effectiveness of therapy or of prognosis will need to be confirmed by correlations with clinical outcome.

Biomarkers, Tumor↗

PubMed2003

Detection of circulating MN/CA9 positive renal cell carcinoma cells during operation.

Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30 % of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100 %. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.

Adult↗

PubMed1978

Destruction of circulating leukemia cells by phagocytosis in rats with myelogenous leukemia.

Acute myelogenous leukemia was induced in outbred Long-Evans rats by iv injections of leukemia cells from a subcutaneous tumor of Shay myelogenous leukemia. In rats with this leukemia the peripheral white blood cell (WBC) counts varied from 2.4 to 700 X 10(9)/liter. No differences were found in the bone marrow of the rats with the high WBC counts and that of rats with low WBC counts. This observation could explain the large variations in the number of circulating leukemia cells caused by differences in cell proliferation or delivery of cells into the circulation. Massive phagocytosis of leukemia cells occurred in animals with low WBC counts (less than 12 X 10(9)/liter) but not in animals with high WBC counts (greater than 150 X 10(9)/liter). This phagocytosis was directed against circulating leukemia cells. The main phagocytes were Kupffer's cells of the liver and macrophages of the spleen parenchyma. In addition, phagocytosis occurred in the spleens and bone marrow by intravascular macrophages, which were derived from extravascular sites. The endothelium of the postcapillary venules of the lymph nodes participated in the phagocytosis of circulating leukemia cells while continuing to be the locus of lymphocytic return from circulation to lymphatic parenchyma. The factors underlying the differences in macrophage activity between the rats with high and low WBC counts were unknown.

Animals↗

PubMed2002

[Clinical significance for detection of circulating cancer cells in renal cell carcinoma].

Renal cell carcinoma has a very poor prognosis since various therapeutic modalities other than radical operation are not effective. Early detection and treatment are of considerable importance to cure the patients; however, early diagnosis of renal cell carcinoma is not easy because no specific tumor marker, like PSA for prostate cancer, is available. MN/CA9 is considered to be one of the carbonic anhydrase isoenzymes, and is expressed in approximately 90% of renal cell carcinomas. Expression of MN/CA9 in normal tissues is very limited. Using optimal RT-PCR with specific primers, MN/CA9 positive cells were clearly detected in the blood. The sensitivity and specificity were found to be approximately 40% and 90% respectively. The detection of circulating renal cell carcinoma cells using RT-PCR for MN/CA9 mRNA is useful for diagnosis of the presence of renal cell carcinomas. This RT-PCR assay may also be able to provide information with which to predict the prognosis of the patients.

Biomarkers, Tumor↗