Detection and Clinical Significance of Lymph Node Micrometastasis Determined by Reverse Transcription-Polymerase Chain Reaction in Patients with Esophageal Carcinoma

Kijima, Fumio; Natsugoe, Shoji; Takao, Sonshin; Aridome, Kuniaki; Baba, Masamichi; Matsushita, Yosuke; Eizuru, Yoshito; Aikou, Takashi

doi:10.1159/000012077

Cited by 51 publications

(34 citation statements)

References 21 publications

(22 reference statements)

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“…CEA is a most commonly used tumor marker for gastrointestinal cancers. Recent studies showed that CEAmRNA RT-PCR or CEA immunostaining is frequently used in detection of micrometastases of gastrointestinal tract cancers [1,12,28,29] . CEA levels in serum play an important role in monitoring patients with gastrointestinal cancer [30][31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

“…KL-1 reacts with cytokeratins (CK), components of intracytoplasmic network of intermediate filaments (Ifs) [4,8,35] , specifically reacts with epithelial tumors. Anti-CK mABs using immunocytochemistry or CK RT-PCR have been widely used for the detection of micrometastases in lymph nodes, venous blood and bone marrow [1,4,12,28,[36][37][38][39][40][41][42] . It is satisfactory using KL-1 monoclonal antibody to detect micrometastasis in the lungs and livers of the mice in this study.…”

Section: Discussionmentioning

confidence: 99%

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Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

Cui

Krueger²,

Henne‐Bruns³

et al. 2001

WJG

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AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis. METHODS Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were i n v e s t i g a t e d b y i m m u n o s t a i n i n g w i t h biotinylated mab KL-1 and by RT-PCR using CK20 specific primers. RESULTS There were totally 9 of 16 surgical s p e c i m e n s g r o w i n g i n n u d e m i c e subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tu m o r . I n t h e g r o u p o f f r e s h t u m o r tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically transplanted tumors resemble the original tumor morphologically and biologically, including T A A e x p r e s s i o n s u c h a s C E A b y immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR. CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new d i a g n o s t i c m e t h o d s a n d t h e r a p e u t i c s t r a t e g i e s f o r m e t a s t a s e s i n c l u d i n g micrometastases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

Cui

Krueger²,

Henne‐Bruns³

et al. 2001

WJG

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“…The reverse transcription-PCR (RT-PCR) assay has been used frequently in recent years for the detection of occult cancer cells or micrometastasis in lymph nodes, bone marrow, and the peritoneal cavity (11)(12)(13)(14)(15). There have been several studies on the molecular detection of circulating cancer cells in the blood by RT-PCR targeted to carcinoembryonic antigen [CEA (16 -18)].…”

Section: Introductionmentioning

confidence: 99%

Carcinoembryonic Antigen Messenger RNA Expression Using Nested Reverse Transcription-PCR in the Peripheral Blood During Follow-up Period of Patients Who Underwent Curative Surgery for Biliary-Pancreatic Cancer

Mataki

Takao

Maemura

et al. 2004

Clinical Cancer Research

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Purpose: Outcome for patients with biliary-pancreatic cancer is still poor, despite curative operation. We investigated the clinical significance of molecular detection of circulating cancer cells in the blood as an early indicator of relapse during follow-up of patients who underwent a curative operation for biliary-pancreatic cancer.Patients and Methods: We followed 53 patients who underwent a curative operation for biliary-pancreatic cancer between 1996 and 2001. We used reverse transcription-PCR in the peripheral blood to evaluate carcinoembryonic antigen (CEA) mRNA expression for molecular detection of circulating cancer cells. Follow-up examinations every 3 months after surgery included CEA mRNA expression in the blood, serum CEA, serum carbohydrate antigen 19-9 (CA19-9), and computed tomography or magnetic resonance imaging.Results: Sixteen of 53 patients (30.2%) were diagnosed with a recurrence by imaging studies. The CEA mRNA detection rate in the peripheral blood of these 16 patients was 75% compared with 5.4% in the 37 patients without relapse (P < 0.001). Sensitivity of CEA mRNA, CEA, and CA19-9 serum levels was 75.0%, 50.0%, and 68.8%, respectively. Similarly, specificity was 94.6%, 64.9%, and 81.1%, respectively. CEA mRNA was expressed in the blood, even though tumor markers CEA and CA19-9 were within the normal range in patients with relapse. CEA mRNA expression in the blood, as well as the serum level of CA19-9, tended to be detected a few months earlier than detection by imaging modalities.Conclusions: During the follow-up of patients who undergo a curative operation for biliary-pancreatic cancer, CEA mRNA expression in the peripheral blood might be a useful and early indicator of relapse.

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“…In recent years, in an attempt to improve the sensitivity of histology in identifying lymph node metastasis, various techniques have been studied, including immunocytochemical analysis, with antibodies elicited towards cancer-specific antigenic determinants, and the molecular detection of cancer cells [2, 6, 7, 8, 9, 10, 11]. The latter approach has received particular attention not only in the identification of lymph node cancer cells, but also in their identification in blood and bone marrow [8, 9, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]: it is highly sensitive, and therefore has great potential in identifying scarce cancer cells (1 cell in a population of 10 7 –10 8 ) [25].…”

Section: Introductionmentioning

confidence: 99%

CEA mRNA Identification in Peripheral Blood Is Feasible for Colorectal, But Not for Gastric or Pancreatic Cancer Staging

Piva

Navaglia²,

Basso³

et al. 2000

Oncology

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Objective: It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer. Methods: We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure. Results: The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (χ² = 14.6, p < 0.01), lymph node (χ² = 18.95, p < 0.001) and distant metastasis (χ² = 11.3, p < 0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis. Conclusions: The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.

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Detection and Clinical Significance of Lymph Node Micrometastasis Determined by Reverse Transcription-Polymerase Chain Reaction in Patients with Esophageal Carcinoma

Cited by 51 publications

References 21 publications

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

Carcinoembryonic Antigen Messenger RNA Expression Using Nested Reverse Transcription-PCR in the Peripheral Blood During Follow-up Period of Patients Who Underwent Curative Surgery for Biliary-Pancreatic Cancer

CEA mRNA Identification in Peripheral Blood Is Feasible for Colorectal, But Not for Gastric or Pancreatic Cancer Staging

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