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Published in: Annals of Surgical Oncology 2/2012

01-02-2012 | Gastrointestinal Oncology

Molecular Detection of Sentinel Node Micrometastases in Patients with Clinical N0 Gastric Carcinoma with Real-time Multiplex Reverse Transcription-Polymerase Chain Reaction Assay

Authors: Yoshimasa Shimizu, MD, Hiroya Takeuchi, MD, PhD, Yasuhiko Sakakura, PhD, Yoshiro Saikawa, MD, PhD, Tadaki Nakahara, MD, PhD, Makio Mukai, MD, PhD, Masaki Kitajima, MD, PhD, Yuko Kitagawa, MD, PhD

Published in: Annals of Surgical Oncology | Issue 2/2012

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Abstract

Purpose

Described is a novel real-time multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay suitable for intraoperative detection of micrometastasis (MM) in sentinel nodes (SNs) dissected from patients with clinical N0 (cN0) gastric carcinoma.

Methods

One hundred three patients with gastric cancer, who were preoperatively diagnosed with cN0 and clinical T1 or T2, were enrolled. The patients underwent SN mapping followed by standard radical gastrectomy with lymph node dissection. In addition to all SNs, non-SNs (NSNs) within the SN lymphatic basin and NSN from a different lymphatic basin were randomly sampled. All SNs and NSNs were examined by routine histologic diagnosis and RT-PCR for the expression of cytokeratin (CK) 19, CK20, and carcinoembryonic antigen (CEA).

Results

The RT-PCR assay and histologic examination were performed in 512 SNs and 299 NSNs from 103 patients. Pathologic l lymph node metastasis was revealed in 13 (12.6%) of 103 patients. All metastatic lymph nodes were identified within SNs. SNs of these 13 patients had positive findings on RT-PCR. Twenty-eight (27.2%) of 103 patients had negative histopathology but positive findings on RT-PCR. In 7 patients (6.8%), SNs were negative but NSNs were positive on RT-PCR. RT-PCR-positive NSNs were present in the same station as corresponding SNs in 3 of these 7 patients and in the same basin as SNs in 4 patients.

Conclusions

The real-time multiplex RT-PCR assay is a useful tool for the detection of MM in SNs and NSNs in patients with gastric cancer.
Literature
1.
go back to reference Wong JH, Cagle LA, Morton DL, et al. Lymphatic drainage of skin to a sentinel node in feline model. Ann Surg. 1991;214:637–41.PubMedCrossRef Wong JH, Cagle LA, Morton DL, et al. Lymphatic drainage of skin to a sentinel node in feline model. Ann Surg. 1991;214:637–41.PubMedCrossRef
2.
go back to reference Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.PubMedCrossRef Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9.PubMedCrossRef
3.
go back to reference Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet. 1997;349:1864–7.PubMedCrossRef Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet. 1997;349:1864–7.PubMedCrossRef
4.
go back to reference Edwards MJ, Martin KD, McMasters KM, et al. Lymphatic mapping and sentinel lymph node biopsy in the staging of melanoma. Surg Oncol. 1998;7:51–7.PubMedCrossRef Edwards MJ, Martin KD, McMasters KM, et al. Lymphatic mapping and sentinel lymph node biopsy in the staging of melanoma. Surg Oncol. 1998;7:51–7.PubMedCrossRef
5.
go back to reference Holmes EC, Moseley HS, Morton DL, et al. A rational approach to the surgical management of melanoma. Ann Surg. 1977;186:481–90.PubMedCrossRef Holmes EC, Moseley HS, Morton DL, et al. A rational approach to the surgical management of melanoma. Ann Surg. 1977;186:481–90.PubMedCrossRef
6.
go back to reference Lee SE, Lee JH, Ryu KW, et al. Sentinel node mapping and skip metastases in patients with early gastric Cancer. Ann Surg Oncol. 2009;16:603–8.PubMedCrossRef Lee SE, Lee JH, Ryu KW, et al. Sentinel node mapping and skip metastases in patients with early gastric Cancer. Ann Surg Oncol. 2009;16:603–8.PubMedCrossRef
7.
go back to reference Kitagawa Y, Kitajima M. Sentinel node mapping for gastric cancer: is the jury still out? Gastric Cancer. 2004;7:135–7.PubMedCrossRef Kitagawa Y, Kitajima M. Sentinel node mapping for gastric cancer: is the jury still out? Gastric Cancer. 2004;7:135–7.PubMedCrossRef
8.
go back to reference Kitagawa Y, Fujii H, Mukai M, et al. Radio-guided sentinel node detection for gastric cancer. Br J Surg. 2002;89:604–8.PubMedCrossRef Kitagawa Y, Fujii H, Mukai M, et al. Radio-guided sentinel node detection for gastric cancer. Br J Surg. 2002;89:604–8.PubMedCrossRef
9.
go back to reference Kitagawa Y, Kitajima M. Gastrointestinal cancer and sentinel node navigation surgery. J Surg Oncol. 2002;79:188–93.PubMedCrossRef Kitagawa Y, Kitajima M. Gastrointestinal cancer and sentinel node navigation surgery. J Surg Oncol. 2002;79:188–93.PubMedCrossRef
10.
go back to reference Saha S, Dan AG, Bilchik AJ, et al. Historical review of lymphatic mapping in gastrointestinal malignancies. Ann Surg Oncol. 2004;11:245S–59S.PubMedCrossRef Saha S, Dan AG, Bilchik AJ, et al. Historical review of lymphatic mapping in gastrointestinal malignancies. Ann Surg Oncol. 2004;11:245S–59S.PubMedCrossRef
11.
go back to reference Takeuchi H, Kitajima M, Kitagawa Y, et al. Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cells. Cancer Sci. 2008;99:441–50.PubMedCrossRef Takeuchi H, Kitajima M, Kitagawa Y, et al. Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cells. Cancer Sci. 2008;99:441–50.PubMedCrossRef
12.
go back to reference Arigami T, Natsugoe S, Uenosono Y, et al. Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction. Ann Surg. 2006;243:341–7.PubMedCrossRef Arigami T, Natsugoe S, Uenosono Y, et al. Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction. Ann Surg. 2006;243:341–7.PubMedCrossRef
13.
go back to reference Matsuda J, Kitagawa Y, Fujii H, et al. Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer. Ann Surg Oncol. 2004;11:250–4. Matsuda J, Kitagawa Y, Fujii H, et al. Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer. Ann Surg Oncol. 2004;11:250–4.
14.
go back to reference Suo J, Wang Q, Jin HJ, et al. K-19 mRNA RT-PCR in detecting micrometastasis in regional lymph nodes of gastric cancer. World J Gastroenterol. 2006;12:5219–22.PubMed Suo J, Wang Q, Jin HJ, et al. K-19 mRNA RT-PCR in detecting micrometastasis in regional lymph nodes of gastric cancer. World J Gastroenterol. 2006;12:5219–22.PubMed
15.
go back to reference Bilchik AJ, Saha S, Wiese D, et al. Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial. J Clin Oncol. 2001;19:1128–36.PubMed Bilchik AJ, Saha S, Wiese D, et al. Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial. J Clin Oncol. 2001;19:1128–36.PubMed
16.
go back to reference Mori M, Minori K, Inoue H, et al. Detection of cancer micrometastases in lymph node by reverse transcriptase–polymerase chain reaction. Cancer Res. 1995;55:3412–20. Mori M, Minori K, Inoue H, et al. Detection of cancer micrometastases in lymph node by reverse transcriptase–polymerase chain reaction. Cancer Res. 1995;55:3412–20.
17.
go back to reference Fujita Y, Terashima M, Hoshino Y, et al. Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19 and CK20 mRNA in patients with gastric cancer. Gastric Cancer. 2006;9:308–14.PubMedCrossRef Fujita Y, Terashima M, Hoshino Y, et al. Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19 and CK20 mRNA in patients with gastric cancer. Gastric Cancer. 2006;9:308–14.PubMedCrossRef
18.
go back to reference Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 14th ed. Tokyo: Kanehara; 2010. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 14th ed. Tokyo: Kanehara; 2010.
19.
go back to reference Kitagawa Y, Fujii H, Mukai M, et al. The role of sentinel nodes in gastrointestinal cancer. Surg Clin N Am. 2000;80:1799–809.PubMedCrossRef Kitagawa Y, Fujii H, Mukai M, et al. The role of sentinel nodes in gastrointestinal cancer. Surg Clin N Am. 2000;80:1799–809.PubMedCrossRef
20.
go back to reference Kinami S, Fujimura T, Ojima E, et al. PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow. Int J Clin Oncol. 2008;13:320–9.PubMedCrossRef Kinami S, Fujimura T, Ojima E, et al. PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow. Int J Clin Oncol. 2008;13:320–9.PubMedCrossRef
21.
go back to reference Yanagita S, Natsugoe S, Uenosono Y, et al. Detection of micrometastases in sentinel node navigation surgery for gastric cancer. Surg Oncol. 2008;17:203–10.PubMedCrossRef Yanagita S, Natsugoe S, Uenosono Y, et al. Detection of micrometastases in sentinel node navigation surgery for gastric cancer. Surg Oncol. 2008;17:203–10.PubMedCrossRef
22.
go back to reference Gerhard M, Juhl H, Holthoff H, et al. Specific detection of carcinoemboric antigen expressing tumor cells in bone marrow aspirates by polymerase chain reaction. J Clin Oncol. 1994;12:725–9.PubMed Gerhard M, Juhl H, Holthoff H, et al. Specific detection of carcinoemboric antigen expressing tumor cells in bone marrow aspirates by polymerase chain reaction. J Clin Oncol. 1994;12:725–9.PubMed
23.
go back to reference Moll R, Franke WW, Schiller DL, et al. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumor and cultured cells. Cell. 1982;31:11–24.PubMedCrossRef Moll R, Franke WW, Schiller DL, et al. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumor and cultured cells. Cell. 1982;31:11–24.PubMedCrossRef
24.
go back to reference Ruud P, Fodstad O, Hovig E, et al. Identification of a novel cytokeratin19 pseudogene that may interfere with reverse transcriptase–polymerase chain reaction assays used to detect micrometastatic tumor cells. Int J Cancer. 1999;80:119–25.PubMedCrossRef Ruud P, Fodstad O, Hovig E, et al. Identification of a novel cytokeratin19 pseudogene that may interfere with reverse transcriptase–polymerase chain reaction assays used to detect micrometastatic tumor cells. Int J Cancer. 1999;80:119–25.PubMedCrossRef
25.
go back to reference Hoon DS, Wang Y, Dale PS, et al. Detection of occult melanoma cells in blood with a multiple marker polymerase chain reaction assay. J Clin Oncol. 1995;13:2109–16.PubMed Hoon DS, Wang Y, Dale PS, et al. Detection of occult melanoma cells in blood with a multiple marker polymerase chain reaction assay. J Clin Oncol. 1995;13:2109–16.PubMed
26.
go back to reference Okada Y, Fujiwara Y, Yamamoto H, et al. Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase–polymerase chain reaction assay. Cancer. 2001;92:2056–64.PubMedCrossRef Okada Y, Fujiwara Y, Yamamoto H, et al. Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase–polymerase chain reaction assay. Cancer. 2001;92:2056–64.PubMedCrossRef
27.
go back to reference Nakajo A, Natsugoe S, Ishigami S, et al. Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer. Ann Surg Oncol. 2000;8:158–62.CrossRef Nakajo A, Natsugoe S, Ishigami S, et al. Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer. Ann Surg Oncol. 2000;8:158–62.CrossRef
28.
go back to reference Miyake K, Seshimo A, Kameoka S, et al. Assessment of lymph node micrometastasis in early gastric cancer in relation to sentinel nodes. Gastric Cancer. 2006;9:197–202.PubMedCrossRef Miyake K, Seshimo A, Kameoka S, et al. Assessment of lymph node micrometastasis in early gastric cancer in relation to sentinel nodes. Gastric Cancer. 2006;9:197–202.PubMedCrossRef
29.
go back to reference Lee JH, Ryu KW, Kook MC, et al. Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer. J Surg Oncol. 2008;98:331–5.PubMedCrossRef Lee JH, Ryu KW, Kook MC, et al. Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer. J Surg Oncol. 2008;98:331–5.PubMedCrossRef
30.
go back to reference Kitagawa Y, Ohgami M, Fujii H, et al. Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach. Ann Surg Oncol. 2001;8:86–9. Kitagawa Y, Ohgami M, Fujii H, et al. Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach. Ann Surg Oncol. 2001;8:86–9.
31.
go back to reference Ohdaira H, Nimura H, Mitsumori N, et al. Validity of modified gastrectomy combined with sentinel node navigation surgery for early gastric cancer. Gastric Cancer. 2007;10:117–22.PubMedCrossRef Ohdaira H, Nimura H, Mitsumori N, et al. Validity of modified gastrectomy combined with sentinel node navigation surgery for early gastric cancer. Gastric Cancer. 2007;10:117–22.PubMedCrossRef
32.
go back to reference Takeuchi H, Saikawa Y, Kitagawa Y, et al. Laparoscopic sentinel node navigation surgery for early gastric cancer. Asian J Endosc Surg. 2009;2:13–7.CrossRef Takeuchi H, Saikawa Y, Kitagawa Y, et al. Laparoscopic sentinel node navigation surgery for early gastric cancer. Asian J Endosc Surg. 2009;2:13–7.CrossRef
Metadata
Title
Molecular Detection of Sentinel Node Micrometastases in Patients with Clinical N0 Gastric Carcinoma with Real-time Multiplex Reverse Transcription-Polymerase Chain Reaction Assay
Authors
Yoshimasa Shimizu, MD
Hiroya Takeuchi, MD, PhD
Yasuhiko Sakakura, PhD
Yoshiro Saikawa, MD, PhD
Tadaki Nakahara, MD, PhD
Makio Mukai, MD, PhD
Masaki Kitajima, MD, PhD
Yuko Kitagawa, MD, PhD
Publication date
01-02-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 2/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2122-4

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