The pH Levels of Sentinel Lymph Nodes and the Probability of Cancer Involvement in Breast Cancer Patients: a Cross-Sectional Study pH levels of SLN in breast cancer

Maryam Avatefi (1), Zohreh Miripour (2), Fereshte Abasvandi (3), Faeze Aghaei (4), Sepideh Mansouri (5), Seyyed Hossein Miraghaie (6), Parisa Hoseinpour (7), Mohammad Esmaeil Akbari (8), Mohammad Abdolahad (9)
(1) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(2) Nano Bio Electronic Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran; UT&TUMS Cancer Electronics Research Center, Tehran, Iran, Iran, Islamic Republic of,
(3) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Nano Bio Electronic Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran; ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran, Iran, Islamic Republic of,
(4) Nano Bio Electronic Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran, Iran, Islamic Republic of,
(5) UT&TUMS Cancer Electronics Research Center, Tehran, Iran , Iran, Islamic Republic of,
(6) Nano Bio Electronic Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran, Iran, Islamic Republic of,
(7) ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran; SEPAS Pathology Lab, Tehran, Iran, Iran, Islamic Republic of,
(8) Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Iran, Islamic Republic of,
(9) Nano Bio Electronic Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran; UT&TUMS Cancer Electronics Research Center, Tehran, Iran , Iran, Islamic Republic of

Abstract

Background: Cancer cells in lymph nodes can undergo metabolic changes, producing acidic byproducts. Our previous experimental results demonstrated significant pH differences between involved and free lymph nodes (LNs), potentially attributed to the release of these acidic byproducts. However, the accuracy of frozen sections is influenced by pathologists' expertise and limited response time. To address these limitations, we developed a simple pH sensing method.


Methods: In this paper, we conduct a cross-sectional study on non-neoadjuvant breast cancer patients (n= 34) from Shohada Tjarish Hospital and Azar Surgical Clinic to check the agreement between the pH value of sentinel lymph nodes (SLNs) and their pathologic score. To assess the pH assay's validity in detecting metastasized cancer cells in lymph nodes, the sensitivity, specificity, and accuracy of the sensor were calculated using Permanent pathology of LNs as the reference standard.


Results: Results showed that cancer SLNs had pH , while free LNs had pH > 8 (p-value <0.001). The sensitivity and specificity of the data were 89% (95% CI (0.73-1.05)) and 82% (95% CI (0.64-1.00)), respectively.


Conclusion: Hence, in the absence of a frozen section, such a simple measurement may assist the surgeon in deciding whether to dissect a further number of LNs or not.

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References

Jones D, Pereira ER, Padera TP. Growth and immune evasion of lymph node metastasis. Front Oncol. 2018;8:36. doi: 10.3389/fonc.2018.00036.

Pereira ER, Jones D, Jung K, Padera TP. The lymph node microenvironment and its role in the progression of metastatic cancer. Semin Cell Dev Biol. Elsevier; 2015. p. 98–105. doi: 10.1016/j.semcdb.2015.01.008.

Zhang S, Zhang D, Yi S, Gong M, Lu C, Cai Y, et al. The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis. Oncotarget. 2017;8:2863. doi: 10.18632/oncotarget.13752.

Han M, Kang R, Zhang C. Lymph Node Mapping for Tumor Micrometastasis. ACS Biomater Sci Eng. 2022; doi: 10.1021/acsbiomaterials.2c00111.

Goyal A. New technologies for sentinel lymph node detection. Breast care. 2018;13:349–53. doi: 10.1159/000492436.

Kuwahata A, Tanaka R, Matsuda S, Amada E, Irino T, Mayanagi S, et al. Development of magnetic probe for sentinel lymph node detection in laparoscopic navigation for gastric cancer patients. Sci Rep. 2020;10:1–12. doi: 10.1038/s41598-020-58530-5.

Mutter D, Rubino F, Sowinska M, Henri M, Dutson E, Ceulemans R, et al. A new device for sentinel node detection in laparoscopic colon resection. JSLS. 2004;8:347. doi:Not Available

Yang X, Wang Z, Zhang F, Zhu G, Song J, Teng G-J, et al. Mapping sentinel lymph node metastasis by dual-probe optical imaging. Theranostics. 2017;7:153. doi: 10.7150/thno.17085.

Tsuchimochi M, Yamaguchi H, Hayama K, Okada Y, Kawase T, Suzuki T, et al. Imaging of Metastatic Cancer Cells in Sentinel Lymph Nodes using Affibody Probes and Possibility of a Theranostic Approach. Int J Mol Sci. 2019;20:427. doi: 10.3390/ijms20020427.

Choi JW, Cho J, Lee Y, Yim J, Kang B, Oh KK, et al. Microwave detection of metastasized breast cancer cells in the lymph node; potential application for sentinel lymphadenectomy. Breast Cancer Res Treat. 2004;86:107–15. doi: 10.1023/b:brea.0000032979.52773.fb.

Malich A, Fritsch T, Mauch C, Boehm T, Freesmeyer M, Fleck M, et al. Electrical impedance scanning: a new technique in the diagnosis of lymph nodes in which malignancy is suspected on ultrasound. Br J Radiol. 2001;74:42–7. doi: 10.1259/bjr.74.877.740042.

Häyry V, Kågedal Å, Hjalmarsson E, Neves da Silva PF, Drakskog C, Margolin G, et al. Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis. Br J Cancer. 2018;118:421–7. doi: 10.1038/bjc.2017.408.

Togami S, Kawamura T, Fukuda M, Yanazume S, Kamio M, Kobayashi H. Quantitative RT-PCR assay for detecting lymph node metastasis in endometrial cancer: a preliminary study. Oncology. 2019;96:179–82. doi: 10.1159/000493485.

Horsnell JD, Smith JA, Sattlecker M, Sammon A, Christie-Brown J, Kendall C, et al. Raman spectroscopy–a potential new method for the intra-operative assessment of axillary lymph nodes. the surgeon. 2012;10:123–7. doi: 10.1016/j.surge.2011.02.004.

Mahdavi R, Yousefpour N, Abbasvandi F, Ataee H, Hoseinpour P, Akbari ME, et al. Intraoperative pathologically-calibrated diagnosis of lymph nodes involved by breast cancer cells based on electrical impedance spectroscopy; a prospective diagnostic human model study. Int Jour of Surg. 2021;96:106166. doi: 10.1016/j.ijsu.2021.106166.

Hong YT, Yun J, Lee JH, Hong K-H. Smart needle to diagnose metastatic lymph node using electrical impedance spectroscopy. Auris Nasus Larynx. 2021;48:281–7. doi: 10.1016/j.anl.2020.08.011.

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 Res Treat. 2014;148:355–61. doi: 10.1007/s10549-014-3161-x.

Miripour ZS, Aghaee P, Abbasvandi F, Hoseinpour P, Parniani M, Abdolahad M. Real-time diagnosis of sentinel lymph nodes involved to breast cancer based on pH sensing through lipid synthesis of those cells. Biosci Rep. 2020;40. doi: 10.1042/BSR20200970.

Cox CE, Haddad F, Bass S, Cox JM, Ku NN, Berman C, et al. Lymphatic mapping in the treatment of breast cancer. Breast Cancer. 1998;12. doi: Not Available

Cantin J, Scarth H, Levine M, Hugi M, Cancer SC on CPG for the C and T of B. Clinical practice guidelines for the care and treatment of breast cancer: 13. Sentinel lymph node biopsy. Cmaj. 2001;165:166–73. doi: Not Available

Chao C, Wong SL, Ackermann D, Simpson D, Carter MB, Brown CM, et al. Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer. The American journal of surgery. 2001;182:609–15. doi: 10.1016/s0002-9610(01)00794-2.

Wang L, Zhang S, Wang X. The metabolic mechanisms of breast cancer metastasis. Front Oncol. 2021;10:602416. doi: 10.3389/fonc.2020.602416.

Fadaka A, Ajiboye B, Ojo O, Adewale O, Olayide I, Emuowhochere R. Biology of glucose metabolization in cancer cells. Journal of Oncological Sciences. 2017;3:45–51. doi:10.1016/j.jons.2017.06.002

Jiang B. Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis. 2017;4:25–7. doi: 10.1016/j.gendis.2017.02.003.

Wang T, Frangou C, Zhang J. Fatty acid oxidation (FAO) metabolic switch: metastasis in lymph nodes driven by yes-associated protein (YAP) activation. Biotarget. 2019;3. doi: 10.21037/biotarget.2019.07.03.

Lee C, Jeong S, Jang C, Bae H, Kim YH, Park I, et al. Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science (1979). 2019;363:644–9. doi: 10.1126/science.aav0173.

Ubellacker JM, Morrison SJ. Metabolic Adaptation Fuels Lymph Node Metastasis. Cell Metab. 2019;29:785–6. doi: 10.1016/j.cmet.2019.03.006.

Hotton J, Salleron J, Henrot P, Buhler J, Leufflen L, Rauch P, et al. Pre-operative axillary ultrasound with fine-needle aspiration cytology performance and predictive factors of false negatives in axillary lymph node involvement in early breast cancer. Breast Cancer Res Treat. 2020;183:639–47. doi: 10.1007/s10549-020-05830-z.

Authors

Maryam Avatefi
Zohreh Miripour
Fereshte Abasvandi
Faeze Aghaei
Sepideh Mansouri
Seyyed Hossein Miraghaie
Parisa Hoseinpour
Mohammad Esmaeil Akbari
Mohammad Abdolahad
m.abdolahad@ut.ac.ir (Primary Contact)
1.
Avatefi M, Miripour Z, Abasvandi F, Aghaei F, Mansouri S, Miraghaie SH, Hoseinpour P, Akbari ME, Abdolahad M. The pH Levels of Sentinel Lymph Nodes and the Probability of Cancer Involvement in Breast Cancer Patients: a Cross-Sectional Study: pH levels of SLN in breast cancer. Arch Breast Cancer [Internet]. 2024 May 1 [cited 2024 Dec. 10];11(2):191-7. Available from: https://archbreastcancer.com/index.php/abc/article/view/899

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