Comparison of the Diagnostic Value Between Real-Time Reverse Transcription-Polymerase Chain Reaction Assay and Histopathologic Examination in Sentinel Lymph Nodes for Patients With Gastric Carcinoma.

OBJECTIVES Sentinel lymph node (SLN)-based diagnosis in gastric cancers has shown varied sensitivities and false-negative rates in several studies. Application of the reverse transcription-polymerase chain reaction (RT-PCR) in SLN diagnosis has recently been proposed. METHODS A total of 155 SLNs from 65 patients with cT1-2, N0 gastric cancer were examined. The histopathologic results were compared with results obtained by real-time RT-PCR for detecting molecular RNA (mRNA) of cytokeratin (CK)19, carcinoembryonic antigen (CEA), and CK20. RESULTS The sensitivity and specificity of the multiple marker RT-PCR assay standardized against the results of the postoperative histological examination were 0.778 (95% confidence interval [CI], 0.577-0.914) and 0.781 (95% CI, 0.700-0.850), respectively. In comparison, the sensitivity and specificity of intraoperative diagnosis were 0.819 (95% CI, 0.619-0.937) and 1.000 (95% CI, 0.972-1.000), respectively. The positive predictive value of the multiple-marker RT-PCR assay was 0.355 (95% CI, 0.192-0.546) for predicting non-SLN metastasis, which was lower than that of intraoperative diagnosis (0.813, 95% CI, 0.544-0.960). CONCLUSIONS The real-time RT-PCR assay could detect SLN metastasis in gastric cancer. However, the predictive value of the real-time RT-PCR assay was lower than that of precise histopathologic examination and did not outweigh that of our intraoperative SLN diagnosis.

[1]  C. Livasy,et al.  Breast cancer detection in axillary sentinel lymph nodes: the impact of the method of pathologic examination. , 2014, Human pathology.

[2]  N. Magné,et al.  OSNA (one-step nucleic acid amplification) sentinel lymph node intraoperative molecular analysis in breast cancer: a cost-benefit analysis , 2014, Medical Oncology.

[3]  D. Park,et al.  The quantification of HER2 and MYC gene fragments in cell-free plasma as putative biomarkers for gastric cancer diagnosis , 2014, Clinical chemistry and laboratory medicine.

[4]  D. Lips,et al.  The Diagnostic Value of One-Step Nucleic acid Amplification (OSNA) for Sentinel Lymph Nodes in Colon Cancer Patients , 2014, Annals of Surgical Oncology.

[5]  H. Lee,et al.  Effects of Fixation and Storage of Human Tissue Samples on Nucleic Acid Preservation , 2014, Korean journal of pathology.

[6]  H. Tsuda,et al.  Multicenter study evaluating the clinical performance of the OSNA assay for the molecular detection of lymph node metastases in gastric cancer patients , 2013, Gastric Cancer.

[7]  Y. Sagara,et al.  Clinical application of the one-step nucleic acid amplification method to detect sentinel lymph node metastasis in breast cancer , 2013, Breast Cancer.

[8]  M. Kitajima,et al.  Molecular Detection of Sentinel Node Micrometastases in Patients with Clinical N0 Gastric Carcinoma with Real-time Multiplex Reverse Transcription-Polymerase Chain Reaction Assay , 2012, Annals of Surgical Oncology.

[9]  L. Helyer,et al.  What is the accuracy of sentinel lymph node biopsy for gastric cancer? A systematic review , 2012, Gastric Cancer.

[10]  T. Giese,et al.  Molecular detection of breast cancer metastasis in sentinel lymph nodes by reverse transcriptase polymerase chain reaction (RT-PCR): identifying, evaluating and establishing multi-marker panels , 2011, Breast Cancer Research and Treatment.

[11]  Klaus Pantel,et al.  Cell-free nucleic acids as biomarkers in cancer patients , 2011, Nature Reviews Cancer.

[12]  T. Ichikura,et al.  One-Step Nucleic Acid Amplification (OSNA) for the Application of Sentinel Node Concept in Gastric Cancer , 2011, Annals of Surgical Oncology.

[13]  Mehmet Toner,et al.  Circulating tumor cells: approaches to isolation and characterization , 2011, The Journal of cell biology.

[14]  D. Elashoff,et al.  Molecular Upstaging Based on Paraffin-Embedded Sentinel Lymph Nodes: Ten-Year Follow-up Confirms Prognostic Utility in Melanoma Patients , 2011, Annals of surgery.

[15]  R. Orr,et al.  Molecular Detection of Micrometastatic Breast Cancer in Histopathology—Negative Axillary Lymph Nodes Fails to Predict Breast Cancer Recurrence: A Final Analysis of a Prospective Multi-Institutional Cohort Study , 2010, Annals of Surgical Oncology.

[16]  Y. Kitagawa,et al.  Molecular Diagnosis and Translymphatic Chemotherapy Targeting Sentinel Lymph Nodes of Patients with Early Gastrointestinal Cancers , 2010, Digestion.

[17]  T. Ichikura,et al.  Limited Gastrectomy With Dissection of Sentinel Node Stations for Early Gastric Cancer With Negative Sentinel Node Biopsy , 2009, Annals of surgery.

[18]  T. Sano,et al.  Investigation of the Lymphatic Stream of the Stomach in Gastric Cancer with Solitary Lymph Node Metastasis , 2009, World Journal of Surgery.

[19]  I. Choi,et al.  Factors associated with detection failure and false‐negative sentinel node biopsy findings in gastric cancer: Results of prospective single center trials , 2009, Journal of surgical oncology.

[20]  Young Woo Kim,et al.  Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer , 2008, Journal of surgical oncology.

[21]  P. V. van Diest,et al.  Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer , 2008, International journal of cancer.

[22]  M. Kitajima,et al.  Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cells , 2008, Cancer science.

[23]  G. Viale,et al.  Comparative Evaluation of an Extensive Histopathologic Examination and a Real-Time Reverse-Transcription-Polymerase Chain Reaction Assay for Mammaglobin and Cytokeratin 19 on Axillary Sentinel Lymph Nodes of Breast Carcinoma Patients , 2008, Annals of surgery.

[24]  H. Tsuda,et al.  One-step Nucleic Acid Amplification for Intraoperative Detection of Lymph Node Metastasis in Breast Cancer Patients , 2007, Clinical Cancer Research.

[25]  T. Kubota,et al.  Interim Results of Sentinel Node Biopsy during Laparoscopic Gastrectomy: Possible Role in Function-Preserving Surgery for Early Cancer , 2006, World Journal of Surgery.

[26]  S. Natsugoe,et al.  Evaluation of Sentinel Node Concept in Gastric Cancer Based on Lymph Node Micrometastasis Determined by Reverse Transcription-Polymerase Chain Reaction , 2006, Annals of surgery.

[27]  G. Viale,et al.  Pathologic examination of the axillary sentinel lymph nodes in patients with early-stage breast carcinoma: current and resolving controversies on the basis of the European Institute of Oncology experience , 2006, Virchows Archiv.

[28]  A. Purushotham,et al.  The value of immunohistochemistry in sentinel lymph node histopathology in breast cancer , 2005, British Journal of Cancer.

[29]  M. Noguchi,et al.  Therapeutic relevance of breast cancer micrometastases in sentinel lymph nodes , 2002, The British journal of surgery.

[30]  V. Yajnik,et al.  Pathology and genetics of tumors of the digestive system , 2001 .

[31]  Y. Doki,et al.  Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple‐marker reverse transcriptase‐polymerase chain reaction assay , 2001, Cancer.

[32]  A. Luini,et al.  Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma , 2001, Cancer.

[33]  G. Farshid,et al.  Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma , 2000, Cancer.

[34]  M. Noguchi,et al.  Sentinel lymph node biopsy in breast cancer using blue dye with or without isotope localization , 2000, Breast cancer.

[35]  R. Mújica-Mota,et al.  A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer. , 2015, Health technology assessment.

[36]  O. Nieweg,et al.  Sentinel lymph node biopsy. , 2014, Australian family physician.

[37]  D. Park,et al.  Precise Pathologic Examination Decreases the False-Negative Rate of Sentinel Lymph Node Biopsy in Gastric Cancer , 2012, Annals of Surgical Oncology.

[38]  PhD Do Joong Park MD,et al.  Simultaneous Indocyanine Green and 99mTc-Antimony Sulfur Colloid-Guided Laparoscopic Sentinel Basin Dissection for Gastric Cancer , 2010, Annals of Surgical Oncology.

[39]  J. Lang Sentinel node in melanoma patients: triple negativity with routine techniques and PCR as positive prognostic factor for survival , 2009 .

[40]  C. Compton,et al.  AJCC Cancer Staging Manual , 2002, Springer New York.