Evolving Landscape of Intraoperative Evaluation of Sentinel Lymph Node Biopsy in Breast Cancer sentinel lymph node
Abstract
Background: Sentinel lymph node (SLN) biopsy has transformed breast cancer management by providing a minimally invasive method axillary staging and reducing the need for extensive lymph node dissections. Following de-escalation trials such as ACOSOG Z0011, the role of intraoperative SLN evaluation has narrowed, especially for z0011-eligible patients in whom SLN evaluation now rarely alters axillary management. Nevertheless, the intraoperative SLN assessment remains valuable for immediate decision-making, potentially minimising reoperation rates, and improving patient outcomes.
Methods: A literature review was conducted to evaluate intraoperative SLN assessment in breast cancer, with emphasis on histopathological techniques. English language articles from 2010-2025 were identified in PubMed using the combination terms “intraoperative”, “sentinel lymph node(s)”, “breast cancer”, “histopathology”, “pathology”, and “frozen section”. This work was conceived as a narrative review; no formal systematic review procedures or meta-analysis were performed.
Results: This review outlines the historical development of SLN biopsy, highlights key clinical trials supporting its use, and examines current intraoperative assessment techniques, including frozen section analysis, touch imprint cytology, and one-step nucleic acid amplification. The diagnostic accuracy and clinical relevance of each method are discussed, particularly in the context of low-volume disease such as micrometastases and isolated tumour cells, which rarely influence contemporary surgical or radiotherapy decisions.
Conclusion: SLN biopsy remains central to breast cancer staging, but it can be safely omitted in selected patients with early-stage breast cancer. Emerging molecular-probe-based and artificial intelligence- assisted technologies will improve diagnostic accuracy and consistency in intraoperative assessment.
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References
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2024 ;74(3):229–63. /doi: 10.3322/caac.21834.
Cody HS. Clinical aspects of sentinel node biopsy. Breast Cancer Research. 2001 Apr 1;3(2):104–8. doi:10.1186/BCR280
Cabanas RM. An approach for the treatment of penile carcinoma. Cancer. 1977 Feb 1;39(2):456–66. doi:10.1002/1097-0142(197702)39:2<456::AID-CNCR2820390214>3.0.CO;2-I .
Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical Details of Intraoperative Lymphatic Mapping for Early Stage Melanoma. Archives of Surgery. 1992 Apr 1;127(4):392–9. doi:10.1001/ARCHSURG.1992.01420040034005
Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Annals of Surgery. 1994;220(3):391–401. doi: 10.1097/00000658-199409000-00015.
Krag DN. Minimal access surgery for staging regional lymph nodes: The sentinel-node concept. Current Problems in Surgery. 1998;35(11):961–1016. doi:10.1016/s0011-3840(98)80008-7.
Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. A Randomized Comparison of Sentinel-Node Biopsy with Routine Axillary Dissection in Breast Cancer. New England Journal of Medicine. 2003 Aug 7;349(6):546–53. doi:10.1056/NEJMOA012782
Giuliano AE, Hunt KK, Ballman K V., Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis: A Randomized Clinical Trial. Journal of the American Medical Association.2011;305(6):569–75. doi: 10.1001/jama.2011.90
Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg VS, Shriver C, et al. The Sentinel Node in Breast Cancer — A Multicenter Validation Study.The New England Journal of Medicine. 1998 ;339(14):941–6. doi:10.1056/NEJM199810013391401
Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. The Lancet. Oncology. 2006;7(12):983–90. doi:10.1016/S1470-2045(06)70947-0.
Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJH, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): A randomised, multicentre, open-label, phase 3 non-inferiority trial. The Lancet Oncology. 2014;15(12):1303–10. doi:10.1016/S1470-2045(14)70460-7.
Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM, et al. Randomized Multicenter Trial of Sentinel Node Biopsy Versus Standard Axillary Treatment in Operable Breast Cancer: The ALMANAC Trial. Journal of the National Cancer Institute . 2006;98(9):599–609. doi:10.1093/jnci/djj158.
Goyal A, Newcombe RG, Chhabra A, Mansel RE. Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer - Results of the ALMANAC validation phase. Breast Cancer Research and Treatment. 2006;99(2):203–8. Doi: 10.1007/s10549-006-9192-1.
Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: A meta-analysis. Cancer. 2006 Jan 1;106(1):4–16. doi:10.1002/CNCR.21568
Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. 2014;32(13):1365–83. doi:10.1200/JCO.2013.54.1177.
Park KU, Somerfield MR, Anne N, Brackstone M, Conlin AK, Couto HL, et al. Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update. Journal of Clinical Oncology. 2025;43(14):1720–41. doi: 10.1200/JCO-25-00099.
Lyman GH, Somerfield MR, Bosserman LD, Perkins CL, Weaver DL, Giuliano AE. Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. 2017; 35(5):561–4. doi: 10.1200/JCO.2016.71.0947.
Giammarile F, Vidal-Sicart S, Paez D, Pellet O, Enrique EL, Mikhail-Lette M, et al. Sentinel Lymph Node Methods in Breast Cancer. Seminars in Nuclear Medicine. 2022;52(5):551–60. doi: 10.1053/j.semnuclmed.2022.01.006.
Sun SX, Moseley TW, Kuerer HM, Yang WT. Imaging-based approach to axillary lymph node staging and sentinel lymph node biopsy in patients with breast cancer. American Journal of Roentgenology. 2020;214(2):249–58. doi:10.2214/AJR.19.22022.
Barkur S, Notingher I, Rakha E. Intra-operative assessment of sentinel lymph nodes for breast cancer surgery: An update. Surgical Oncology. 2022;40:101678. doi:10.1016/j.suronc.2021.101678.
van der Noordaa MEM, Vrancken Peeters MTFD, Rutgers EJT. The intraoperative assessment of sentinel nodes – Standards and controversies. The Breast. 2017;34:S64–9. doi: 10.1016/j.breast.2017.06.031.
Gal AA. The Centennial Anniversary of the Frozen Section Technique at the Mayo Clinic. Archives of Pathology & Laboratory Medicine. 2005;129(12):1532–5. doi:10.5858/2005-129-1532-TCAOTF.
Taxy JB, Husain AN, Montag AG. Biopsy Interpretation Series Biopsy Interpretation:The Frozen Section. Lippincott Williams & Wilkins; 2009. Chapter 6, Breast and sentinel node; p. 149–155.
Cipolla C, Graceffa G, Cabibi D, Gangi G, Latteri M, Valerio MR, et al. Current Role of Intraoperative Frozen Section Examination of Sentinel Lymph Node in Early Breast Cancer. Anticancer Research. 2020;40:1711–7. doi: 10.21873/anticanres.14124.
Jaafar H. Intra-operative frozen section consultation: concepts, applications and limitations. The Malaysian Journal of Medical Sciences. 2006;13(1):4–12.
Chicken DW, Kocjan G, Falzon M, Lee AC, Douek M, Sainsbury R, et al. Intraoperative touch imprint cytology for the diagnosis of sentinel lymph node metastases in breast cancer. British Journal of Surgery. 2006;93(5):572–6. doi:10.1002/bjs.5289.
Bharath S, Sharma D, Yadav SK, Shekhar S, Jha CK. A Systematic Review and Meta-analysis of Touch Imprint Cytology and Frozen Section Biopsy and Their Comparison for Evaluation of Sentinel Lymph Node in Breast Cancer. World Journal of Surgery. 2023;47(2):478–88. doi: 10.1007/s00268-022-06800-w.
Nakabayashi K, Kaneko T, Iwase T, Akiyama F, Tsuda H, Ueda S, et al. One-step Nucleic Acid Amplification for Intraoperative Detection of Lymph Node Metastasis in Breast Cancer Patients. Clinical Cancer Research. 2007;13(16):48074816. doi:10.1158/1078-0432.CCR-06-2512
Tiernan JP, Verghese ET, Nair A, Pathak S, Kim B, White J, et al. Systematic review and meta-analysis of cytokeratin 19-based one-step nucleic acid amplification versus histopathology for sentinel lymph node assessment in breast cancer. British Journal of Surgery. 2014;101(4):298–306. doi: 10.1002/bjs.9386.
Tamaki 30. One-step nucleic acid amplification assay (OSNA) for sentinel lymph node biopsy. Breast Cancer. 2015;22(3):230–4. Doi: 10.1007/s12282-012-0390-x.
Visser M, Jiwa M, Horstman A, Brink AATP, Pol RP, Van Diest P, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. International Journal of Cancer. 2008;122(11):2562–7. doi: 10.1002/ijc.23451.
Fujisue M, Nishimura R, Okumura Y, Tashima R, Nishiyama Y, Osako T, et al. Clinical significance of CK19 negative breast cancer. Cancers (Basel). 2013;5(1):1–11. doi: 10.3390/cancers5010001.
Vilardell F, Novell A, Martin J, Santacana M, Velasco A, Díez-Castro MJ, et al. Importance of assessing CK19 immunostaining in core biopsies in patients subjected to sentinel node study by OSNA. Virchows Archiv. 2012;460(6):569–75.doi:10.1007/s00428-012-1241-z.
Liu M, Wang W, Wang Y. The diagnostic performance of the one-step nucleic acid amplification assay for the detection of sentinel lymph node metastases in cytokeratin 19-positive breast cancer: a PRISMA-compliant meta-analysis. Frontiers in Medicine. 2024; 11:1391621. doi: 10.3389/fmed.2024.1391621.
Yoneto T, Ikiuo F, Koyanagi N, Yoshimoto T, Takeda Y. Sentinel Lymph Node Biopsy Predicts Non-Sentinel Lymph Node Metastases and Supports Omission of Axillary Lymph Node Dissection in Breast Cancer Patients. Journal of Clinical Medicine. 20251;14(10). doi:10.3390/jcm14103441.
Huxley N, Jones-Hughes T, Coelho H, Snowsill T, Cooper C, Meng Y, 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. Health Technology Assessment. 2015;19(2):1–246. doi: 10.3310/hta19020.
Alexiou GA, Vartholomatos G, Goussia A, Batistatou A, Tsamis K, Voulgaris S, et al. Fast cell cycle analysis for intraoperative characterization of brain tumor margins and malignancy. Journal of Clinical Neuroscience. 2015;22(1):129–32. doi:10.1016/j.jocn.2014.05.029
Jagric T, Mis K, Gorenjak M, Goropevsek A, Kavalar R, Mars T. Can flow cytometry reinvent the sentinel lymph node concept in gastric cancer patients? Journal of Surgical Research. 2018;223:46–57. doi:10.1016/J.JSS.2017.10.018.
Vartholomatos G, Harissis H, Andreou M, Tatsi V, Pappa L, Kamina S, et al. Rapid Assessment of Resection Margins During Breast Conserving Surgery Using Intraoperative Flow Cytometry. Clinical Breast Cancer. 2021:e602–10.doi: 10.1016/j.clbc.2021.03.002.
Liaropoulos I, Liaropoulos A, Liaropoulos K. Critical Assessment of Cancer Characterization and Margin Evaluation Techniques in Brain Malignancies: From Fast Biopsy to Intraoperative Flow Cytometry. Cancers (Basel). 2023;15(19). doi:10.3390/CANCERS15194843
Chen Y, Wang C, Zhao Y. A commentary on “Detection of cancer cells and tumor margins during colorectal cancer surgery by intraoperative flow cytometry.” International Journal of Surgery. 2023;109(11):3669–70. doi:10.1097/JS9.0000000000000599
Hellmich L, Witte KE, Ebinger M, Ulmer A. Flow Cytometry for Detection and Quantification of Micrometastases in Sentinel Lymph Nodes from Patients with Primary Melanoma. Journal of Surgical Research. 2021;257:477–85. doi:10.1016/J.JSS.2020.08.028,
Leers MPG, Schoffelen RHMG, Hoop JGM, Theunissen PHMH, Nap M, Oosterhuis JWA, et al. Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer. Journal of Clinical Pathology. 2002;55(5):359–66. doi:10.1136/JCP.55.5.359.
Balog J, Sasi-Szabó L, Kinross J, Lewis MR, Muirhead LJ, Veselkov K, et al. Intraoperative tissue identification using rapid evaporative ionization mass spectrometry. Science Translational Medicine. 2013;5(194):194ra93.doi: 10.1126/scitranslmed.3005623.
Pekov SI, Bormotov DS, Bocharova SI, Sorokin AA, Derkach MM, Popov IA. Mass spectrometry for neurosurgery: Intraoperative support in decision-making. Mass Spectrometry Reviews. 2025;44(1):62–73. doi: 10.1002/mas.21883.
Malonek D, Dekel BZ, Haran G, Reens-Carmel R, Groisman GM, Hallak M, et al. Rapid intraoperative diagnosis of gynecological cancer by ATR-FTIR spectroscopy of fresh tissue biopsy. Journal of Biophotonics. 2020;13(9):e202000114. doi:10.1002/jbio.202000114.
Hänel L, Kwiatkowski M, Heikaus L, Schlüter H. Mass Spectrometry-Based Intraoperative Tumor Diagnostics. Future Science OA. 2019;5(3). doi:10.4155/FSOA-2018-0087
Garza KY, King ME, Nagi C, Dehoog RJ, Zhang J, Sans M, et al. Intraoperative Evaluation of Breast Tissues During Breast Cancer Operations Using the MasSpec Pen. JAMA Network Open. 2024;7(3):e242684–e242684. doi:10.1001/jamanetworkopen.2024.2684
Tian P, Zhang W, Zhao H, Lei Y, Cui L, Zhang Y, et al. Intraoperative detection of sentinel lymph node metastases in breast carcinoma by Fourier transform infrared spectroscopy. British Journal of Surgery. 2015;102(11):1372–9. doi:10.1002/BJS.9882.
Su KY, Lee WL. Fourier Transform Infrared Spectroscopy as a Cancer Screening and Diagnostic Tool: A Review and Prospects. Cancers. 2020;12(1):115. doi: 10.3390/cancers12010115.
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science. 1991;254(5035):1178–81. doi:10.1126/SCIENCE.1957169, PubMed PMID: 1957169.
Boppart SA, Luo W, Marks DL, Singletary KW. Optical coherence tomography: Feasibility for basic research and image-guided surgery of breast cancer. Breast Cancer Research Treatment. 2004;84(2):85–97.doi:10.1023/B:BREA.0000018401.13609.54.
Nguyen FT, Zysk AM, Chaney EJ, Kotynek JG, Oliphant UJ, Bellafiore FJ, et al. Intraoperative evaluation of breast tumor margins with optical coherence tomography. Cancer Research. 2009;69(22):8790–6. doi:10.1158/0008-5472.CAN-08-4340,.
Luo W, Nguyen F, Zysk A, Ralston T, Brockenbrough J, Marks D, et al. Optical Biopsy of Lymph Node Morphology using Optical Coherence Tomography. Technology In Cancer Research & Treatment.2005;4(5):539–48.doi: 10.1177/153303460500400507
Muijzer MB, Schellekens PAWJ, Beckers HJM, de Boer JH, Imhof SM, Wisse RPL. Clinical applications for intraoperative optical coherence tomography: a systematic review. Eye. 2022;36(2):379. doi:10.1038/S41433-021-01686-9.
Grieve K, Mouslim K, Assayag O, Dalimier E, Harms F, Bruhat A, et al. Assessment of Sentinel Node Biopsies With Full-Field Optical Coherence Tomography. Technology in Cancer Research & Treatment. 2016;15(2):266–74.doi:10.1177/1533034615575817.
Poling JS, Tsangaris TN, Argani P, Cimino-Mathews A. Frozen section evaluation of breast carcinoma sentinel lymph nodes: a retrospective review of 1,940 cases. Breast Cancer Research and Treatment . 2014;148:355–61. doi:10.1007/s10549-014-3161-x
Ahmed Elshanbary A, Abdelsameia Awad A, Abdelsalam A, Ibrahim IH, Abdel-Aziz W, Bahaaeldin Darwish Y, et al. The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis. Environmental Science and Pollution Research. 2022; 29(32):47931-41. doi:10.1007/s11356-022-20569-4
Lumachi F, Marino F, Zanella S, Chiara GB, Basso SMM. Touch Imprint Cytology and Frozen-section Analysis for Intraoperative Evaluation of Sentinel Nodes in Early Breast Cancer. Anticancer Research. 2012;32(8):3523–6.
Banerjee SM, Michalopoulos N V., Williams NR, Davidson T, El Sheikh S, McDermott N, et al. Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: Experience from a London Teaching Hospital. The Breast. 2014;23(4):378–84. doi:10.1016/J.BREAST.2014.02.001.
Castellano I, Macrì L, Deambrogio C, Balmativola D, Bussone R, Ala A, et al. Reliability of Whole Sentinel Lymph Node Analysis by One-Step Nucleic Acid Amplification for Intraoperative Diagnosis of Breast Cancer Metastases. Annals of Surgery. 2012;255(2):334–42. doi: 10.1097/SLA.0b013e31823000ed.
Alexiou G. Vartholomatos G, Intraoperative Flow Cytometry. Springer, Cham;2023. Chapter 5, Basic principles; p.49–56. doi: 10.1007/978-3-031-33517-4_4.
Leslie LS, Wrobel TP, Mayerich D, Bindra S, Emmadi R, Bhargava R. High Definition Infrared Spectroscopic Imaging for Lymph Node Histopathology. PLoS One. 2015;10(6):e0127238. doi:10.1371/JOURNAL.PONE.0127238.
Su MI, Chen CY, Yeh HI, Wang K Te. Concise Review of Optical Coherence Tomography in Clinical Practice. Acta Cardiologica Sinica. 2016;32(4):381. doi:10.6515/acs20151026a
Faragalla H, Davoudi B, Nofech-Moses N, Yucel Y, Jakate K. The Use of Optical Coherence Tomography for Gross Examination and Sampling of Fixed Breast Specimens: A Pilot Study. Diagnostics. 2022;12(9). doi:10.3390/DIAGNOSTICS12092191.
Akay CL, Albarracin C, Torstenson T, Bassett R, Mittendorf EA, Yi M, et al. Factors impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer. The Breast Journal. 2018;24(1):28–34. doi:10.1111/TBJ.12829.
Ahuja S, Yadav P, Fattahi-Darghlou M, Zaheer S. Comparison of Intraoperative Imprint Cytology versus Frozen Section for Sentinel Lymph Node Evaluation in Breast Cancer. A study along with Systematic Review and Meta-analysis of literature. Asian Pacific Journal of Cancer Prevention. 2024;25(4):1113-19. doi: 10.31557/APJCP.2024.25.4.1113..
Galimberti V, Cole BF, Viale G, Veronesi P, Vicini E, Intra M, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. The Lancet Oncology. 2018;19(10):1385–93. doi:10.1016/S1470-2045(18)30380-2.
Montagna G, Laws A, Ferrucci M, Mrdutt MM, Sun SX, Bademler S, et al. Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study. Journal of Clinical Oncology. 2025;43(7):810–20. doi:10.1200/JCO.24.01052.
Chan YHY, Hung WK, Mak KL, Ying MWL, Chan MCM, Lui CY. Intra-operative Assessment of Axillary Sentinel Lymph Nodes by Frozen Section-An Observational Study of 260 Procedures. Asian Journal of Surgery. 2011;34(2):81–5. doi: 10.1016/S1015-9584(11)60024-9.
Arlicot C, Le Louarn A, Arbion F, Leveque J, Lorand S, Kinn J, et al. Evaluation of the Two Intraoperative Examination Methods for Sentinel Lymph Node Assessment: A Multicentric and Retrospective Study on more than 2,000 Nodes. Anticancer Research. 2013;33:1045–52.
Hashmi A, Faridi N, Khurshid A, … HNAPJ, 2013 undefined. Accuracy of frozen section analysis of sentinel lymph nodes for the detection of Asian breast cancer micrometastasis-experience from Pakistan. Asian Pacific Journal of Cancer Prevention. 2013;14(4):2657–62. doi:10.7314/APJCP.2013.14.4.2657
Barakat FH, Sulaiman I, Sughayer MA. Reliability of frozen section in breast sentinel lymph node examination. Breast Cancer. 2014;21(5):576–82. doi:10.1007/S12282-012-0431-5.
Wong J, Yong WS, Thike AA. False negative rate for intraoperative sentinel lymph node frozen section in patients with breast cancer: a retrospective analysis of patients in a single Asian institution. Journal of Clinical Pathology. 2015; 68(7):536-40. doi: 10.1136/jclinpath-2014-202799.
Qiao G, Cong Y, Zou H, Lin J, Wang X, Li X, et al. False-negative frozen section of sentinel lymph node biopsy in a Chinese population with breast cancer. Anticancer Research. 2016 ;36(3):1331–7.
Tan J, Joblin L, Davenport E. Accuracy of frozen sections for breast cancer sentinel lymph node biopsies within a peripheral New Zealand hospital. The New Zealand Medical Journal. 2016;129(1431):46–50.
Russo L, Betancourt L, Romero G, Godoy A, Bergamo L, Delgado R, et al. Frozen section evaluation of sentinel lymph nodes in breast carcinoma: a retrospective analysis. E-cancer Medical Science. 2017;11:774–83. doi:10.3332/ecancer.2017.774
Lai SK, Masir N, Hayati S, Pauzi MD. Intraoperative frozen section sentinel lymph node assessment in breast cancer: A tertiary institution experience. The Malaysian Journal of Pathology. 2018;40(2):121–8.
Gupta S, Kadayaprath G, Ambastha R, Shakti ·, Shrivastava S. False Negative Rate of Sentinel Lymph Node Biopsy on Intraoperative Frozen Section in Early Breast Cancer Patients: An Institutional Experience. Indian Journal of Surgery Oncology. 2022;13(2):312–5. doi:10.1007/s13193-021-01458-7
Novis E, Kim TJ, Gauci C, Mui J, Gao Y, Garibotto N. Efficacy of frozen section in sentinel lymph node biopsy in early breast cancer – An Australian single-centre experience. Surgery in Practice and Science. 2023;15:100224. doi:10.1016/J.SIPAS.2023.100224.
Van de Vrande S, Meijer J, Rijnders A, Klinkenbijl J. The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer. European Journal of Surgical Oncology. 2009;35:276–80. doi: 10.1016/j.ejso.2008.07.016.
Chiappa C, Rovera F, Corben AD, Fachinetti A, De Berardinis V, Marchionini V, et al. Surgical margins in breast conservation. International Journal of Surgery. 2013;11(S1):S69–72. doi:10.1016/S1743-9191(13)60021-7.
Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. New England Journal of Medicine. 2017;377(19):1836–46. doi: 10.1056/NEJMoa1701830.
Pick L. A rapid method of preparing permanent sections for microscopical diagnosis. British Medical Journal. 1897;1(1881):140–1. doi:10.1136/BMJ.1.1881.140-A.
Fisher JE, Burger PC, Perlman EJ, Dickman PS, Parham DM, Savell, VH, et al. The frozen section yesterday and today: Pediatric solid tumors - Crucial issues. Pediatric and Developmental Pathology. 2001;4(3):252–66. doi:10.1007/S100240010177.
Zhang X, Liu J, Yan X. Rapid intraoperative immunocytochemistry of central nervous system tumors. International Journal of Clinical and Experimental Pathology. 2020;13(1):44–8.
Grahek M, Ptak A, Kalyuzhny AE. High-sensitivity IHC detection of phosphorylated p27/kip1 in human tissues using secondary antibody conjugated to polymer-HRP. Methods in Molecular Biology. 2017;1554:211–8. doi:10.1007/978-1-4939-6759-9_14.
Skaland I, Nordhus M, Gudlaugsson E, Klos J, Kjellevold KH, Janssen EAM, et al. Evaluation of 5 Different Labeled Polymer Immunohistochemical Detection Systems. Applied Immunohistochemistry and Molecular Morphology. 2010;18(1):90–6. doi:10.1097/PAI.0B013E3181B0EAAD.
Chilosi M, Lestani M, Pedron S, Montagna L, Benedetti A, Pizzolo G, et al. A rapid lmmunostaining method for frozen sections. Biotechnic and Histochemistry. 1994;69(4):235–9. doi:10.3109/10520299409106292.
Onishi T, Matsuda S, Nakamura Y, Kuramoto J, Tsuruma A, Sakamoto S, et al. Magnetically Promoted Rapid Immunofluorescence Staining for Frozen Tissue Sections. Journal of Histochemistry and Cytochemistry. 2019;67(8):575–87. doi:10.1369/0022155419841023.
Moriya J, Tanino MA, Takenami T, Endoh T, Urushido M, Kato Y, et al. Rapid immunocytochemistry based on alternating current electric field using squash smear preparation of central nervous system tumors. Brain Tumor Pathology. 2016;33(1):13–8. doi:10.1007/S10014-015-0238-0.
Manuel SL, Johnson BW, Frevert CW, Duncan FE. Revisiting the scientific method to improve rigor and reproducibility of immunohistochemistry in reproductive science. Biology of Reproduction. 2018;99(4):673–7. doi:10.1093/BIOLRE/IOY094.
Baker M. Blame it on the antibodies. Nature. 2015;521(7552):274–6. doi:10.1038/521274A.
Baker M. When antibodies mislead: the quest for validation. Nature. 2020;585(7824):313–4. doi:10.1038/D41586-020-02549-1
Etoc F, Balloul E, Vicario C, Normanno D, Liße D, Sittner A, et al. Non-specific interactions govern cytosolic diffusion of nanosized objects in mammalian cells. Nature Materials. 2018;17(8):740–6. doi:10.1038/s41563-018-0120-7
Verhaar ER, Woodham AW, Ploegh HL. Nanobodies in cancer. Seminars in Immunology. 2021;52:101425. doi: 10.1016/j.smim.2020.101425.
Bedford R, Tiede C, Hughes R, Curd A, McPherson MJ, Peckham M, et al. Alternative reagents to antibodies in imaging applications. Biophysical Reviews. 2017;9(4):299–308. Doi: 10.1007/s12551-017-0278-2.
Jin BK, Odongo S, Radwanska M, Magez S. NANOBODIES®: A Review of Diagnostic and Therapeutic Applications. International Journal of Molecular Sciences. 2023;24(6):5994. doi:10.3390/IJMS24065994.
Ståhl S, Gräslund T, Eriksson Karlström A, Frejd FY, Nygren PÅ, Löfblom J. Affibody Molecules in Biotechnological and Medical Applications. Trends in Biotechnology. 2017;35(8):691–712. doi:10.1016/J.TIBTECH.2017.04.007.
Contreras-Llano LE, Tan C. High-throughput screening of biomolecules using cell-free gene expression systems. Synthetic Biology (Oxford). 2018;3(1). doi:10.1093/SYNBIO/YSY012.
Zhang L, Zhang H. Recent advances of affibody molecules in biomedical applications. Bioorganic & Medicinal Chemistry. 2024;113. doi:10.1016/j.bmc.2024.117923.
Ståhl S, Lindberg H, Hjelm LC, Löfblom J, Leitao CD. Engineering of Affibody Molecules. Cold Spring Harb Protocols. 2024;(11): pdb.top107760. doi: 10.1101/pdb.top107760.
Sexton K, Tichauer K, Samkoe KS, Gunn J, Hoopes PJ, Pogue BW. Fluorescent Affibody Peptide Penetration in Glioma Margin Is Superior to Full Antibody. PLoS One. 2013;8(4). doi:10.1371/JOURNAL.PONE.0060390.
Tuerk C, Gold L. Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase. Science. 1990;249(4968):505–10. doi:10.1126/SCIENCE.2200121.
Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990 346:6287. 1990;346(6287):818–22. doi:10.1038/346818a0.
Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nature Reviews Drug Discovery. 2010;9(7):537–50. doi:10.1038/NRD3141.
Gelinas AD, Davies DR, Janjic N. Embracing proteins: Structural themes in aptamer-protein complexes. Current Opinion in Structural Biology. 2016;36:122–32. doi:10.1016/j.sbi.2016.01.009.
Morozov D, Mironov V, Moryachkov R V., Shchugoreva IA, Artyushenko P V., Zamay GS, et al. The role of SAXS and molecular simulations in 3D structure elucidation of a DNA aptamer against lung cancer. Molecular Therapy Nucleic Acids. 2021;25:316–27. doi:10.1016/j.omtn.2021.07.015
Tivon Y, Falcone G, Deiters A. Protein Labeling and Crosslinking by Covalent Aptamers. Angewandte Chemie ( International Edition in English). 2021 Jul 12;60(29):15899–904. doi:10.1002/ANIE.202101174.
Tabuchi Y, Yang J, Taki M. Relative Nuclease Resistance of a DNA Aptamer Covalently Conjugated to a Target Protein. International Journal of Molecular Sciences. 2022 Jul;23(14). doi:10.3390/IJMS23147778.
Zeng Z, Zhang P, Zhao N, Sheehan AM, Tung CH, Chang CC, et al. Using oligonucleotide aptamer probes for immunostaining of formalin-fixed and paraffin-embedded tissues. Modern Pathology. 2010;23(12):1553–8. doi:10.1038/modpathol.2010.151.
Sun H, Tan W, Zu Y. Aptamers: versatile molecular recognition probes for cancer detection. Analyst. 2016;141(2):403–15. doi:10.1039/C5AN01995H.
Shigdar S, Qian C, Lv L, Pu C, Li Y, Li L, et al. The Use of Sensitive Chemical Antibodies for Diagnosis: Detection of Low Levels of Epcam in Breast Cancer. PLoS One. 2013;8(2):e57613. doi:10.1371/JOURNAL.PONE.0057613
Pu Y, Liu Z, Lu Y, Yuan P, Liu J, Yu B, et al. Using DNA aptamer probe for immunostaining of cancer frozen tissues. Analytical Chemistry. 2015;87(3):1919–24. doi:10.1021/AC504175H.
Tanino M, Sasajima T, Nanjo H, Akesaka S, Kagaya M, Kimura T, et al. Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors. Brain Tumor Pathology. 2015;32(1):12–9. doi:10.1007/S10014-014-0188-Y.
Imai K, Nanjo H, Takashima S, Hiroshima Y, Atari M, Matsuo T, et al. Intraoperative diagnosis of lymph node metastasis during segmentectomy for non-small cell lung cancer by rapid immunohistochemistry using noncontact alternating current electric field mixing. Thoracic Cancer. 2020;11(12):3547–54. doi:10.1111/1759-7714.13699
Terata K, Saito H, Nanjo H, Hiroshima Y, Ito S, Narita K, et al. Novel rapid-immunohistochemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer. Scientific Reports. 2017;7(1):1–9. doi:10.1038/s41598-017-02883-x
Imai K, Nanjo H, Shigeeda W, Sugai T, Ito T, Maniwa Y, et al. Intraoperative rapid immunohistochemistry with noncontact antibody mixing for undiagnosed pulmonary tumors. Cancer Science. 2023;114(2):702–11. doi:10.1111/CAS.15616.
Inoue A, Watanabe H, Kondo T, Katayama E, Miyazaki Y, Suehiro S, et al. Usefulness of intraoperative rapid immunohistochemistry in the surgical treatment of brain tumors. Neuropathology. 2023;43(3):209–20. doi:10.1111/NEUP.12864.
Toda H, Minamiya Y, Kagaya M, Nanjo H, Akagami Y, Saito H, et al. A Novel Immunohistochemical Staining Method Allows Ultrarapid Detection of Lymph Node Micrometastases While Conserving Antibody. Acta Histochemica et Cytochemica. 2011;44(3):133–9. doi:10.1267/AHC.11006
Inoue F, Dina PR, De Los Santos J, Molina M, Cobo CA, Marcos ME, et al. JP2020108336A - Biological cell granular frozen body preparation tool - Google Patents. 2020. https://patents.google.com/patent/JP2020108336A/en?oq=JP2020108336A
Zhao SQ, Wang JJ, Wu J V., Zhang Z. WO2015171938A1 - Direct immunohistochemistry assay - Google Patents 2015.https://patents.google.com/patent/WO2015171938A1/en?oq=WO2015171938A1
Wu J V., Chen S, Zhao S, Wang J. WO2023076000A1 - A method and apparatus for rapid circulating tissue pretreatment - Google Patents. 2023. Available from: https://patents.google.com/patent/WO2023076000A1/en?oq=WO%2f2023%2f076000
CN112236677A - Direct immunohistochemical and immunocytochemical methods - Google Patents. 2019.https://patents.google.com/patent/CN112236677A/en?oq=CN112236677A
CN113391059A - Micropolymer-HRP-nano antibody compound and preparation method thereof - Google Patents.2021.https://patents.google.com/patent/CN113391059A/en?oq=CN113391059A
Mohs PolyDetector DAB HRP Brown IHC Detection System - Bio SB. https://www.biosb.com/biosb-products/mohs-mouse-rabbit-polydetector-dab-hrp-brown-ihc-detection-system/
Lovchik RD, Taylor D, Kaigala G. Rapid micro-immunohistochemistry. Microsystems & Nanoengineering. 2020;6(1). doi:10.1038/S41378-020-00205-2.
Heidinger M, Weber WP. Axillary Surgery for Breast Cancer in 2024. Cancers. Multidisciplinary Digital Publishing Institute (MDPI). 2024;16 (1623). doi:10.3390/cancers16091623
Goyal A, Mann GB, Fallowfield L, Duley L, Reed M, Dodwell D, et al. POSNOC-POsitive Sentinel NOde: Adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: A randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes. BMJ Open. 2021;11(12). doi:10.1136/bmjopen-2021-054365.
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