Assessment of Tumor Cell Death After Percutaneous Ultrasound– Guided Radiofrequency Ablation of Breast Carcinoma: A Prospective Study
Abstract
Background: Current trends in breast cancer treatment include the use of less aggressive surgeries to reduce morbidity, shorten hospital stays and improve cosmetic results. The aim of the study is to assess tumor cell viability after percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for small breast cancer by a combination of staining techniques.
Methods: A prospective study was conducted at a single institution from 2013 to 2017. Twenty women with invasive ductal carcinoma of the breast measuring ≤ 20 mm were treated with US-guided RFA followed immediately by surgical resection. Tumor viability pre- and post-RFA was assessed with Hematoxylin and Eosin (H&E), Nicotinamide adenine dinucleotide (NADH), Succinate dehydrogenase (SDH), Cytochrome c oxidase (COX), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Cytokeratin 18 and 19 (CK18/CK19) staining techniques. Outcomes and correlation with the different techniques were evaluated with principal component analysis Cronbach’s alpha.
Results: Oxidative enzymes in frozen sections showed loss of SDH and NADH in 13 of the 16 tumors (81%) and COX in 11 of the 13 tumors (84%). In paraffin-embedded tissues, CK18 was negative or markedly reduced in 98% and CK19 in 100% of the cases. Lack of evidence of cell death was seen in 3 cases where the maximum temperature achieved at the center of the tumor was ≤ 70ºC. The reliability and internal consistency between the different staining techniques was high (Cronbach’s alpha, 0.8), with concordance between the staining results of the oxidative enzymes and of CK18/CK19.
Conclusion: Loss of tumor viability in small breast tumors after US-guided percutaneous RFA could be assessed in our series with different staining methods. CK18 and CK19 could be used in paraffin-embedded tissues as surrogate markers of tumor cell viability after immediate RFA.
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References
Fleming MM, Holbrook AI, Newell MS. Update on image-guided percutaneous ablation of breast cancer. American Journal of Roentgenology. 2017;208(2):267-74.
Peek MC, Ahmed M, Napoli A, Usiskin S, Baker R, Douek M. Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis. International Journal of Hyperthermia. 2017;33(2):191-202.
Chen J, Zhang C, Li F, Xu L, Zhu H, Wang S, et al. A meta-analysis of clinical trials assessing the effect of radiofrequency ablation for breast cancer. OncoTargets and therapy. 2016;9:1759.
Schässburger K-U, Löfgren L, Lagerstedt U, Leifland K, Thorneman K, Sandstedt B, et al. Minimally-invasive treatment of early stage breast cancer: a feasibility study using radiofrequency ablation under local anesthesia. The Breast. 2014;23(2):152-8.
Waaijer L, Kreb D, Gallardo MF, Van Rossum P, Postma E, Koelemij R, et al. Radiofrequency ablation of small breast tumours: evaluation of a novel bipolar cool-tip application. European Journal of Surgical Oncology (EJSO). 2014;40(10):1222-9.
Organ L. Electrophysiologic principles of radiofrequency lesion making. Stereotactic and Functional Neurosurgery. 1976;39(2):69-76.
Jeffrey SS, Birdwell RL, Ikeda DM, Daniel BL, Nowels KW, Dirbas FM, et al. Radiofrequency ablation of breast cancer: first report of an emerging technology. Archives of Surgery. 1999;134(10):1064-8.
Earashi M, Noguchi M, Motoyoshi A, Fujii H. Radiofrequency ablation therapy for small breast cancer followed by immediate surgical resection or delayed mammotome excision. Breast Cancer. 2007;14(1):39-47.
Seki K, Tsuda H, Iwamoto E, Kinoshita T. Histopathological effect of radiofrequency ablation therapy for primary breast cancer, with special reference to changes in cancer cells and stromal structure and a comparison with enzyme histochemistry. Breast cancer. 2011;18(1):18-23.
Manenti G, Scarano AL, Pistolese CA, Perretta T, Bonanno E, Orlandi A, et al. Subclinical breast cancer: minimally invasive approaches. Our experience with percutaneous radiofrequency ablation vs. cryotherapy. Breast care. 2013;8(5):356-60.
Noguchi M, Motoyoshi A, Earashi M, Fujii H. Long-term outcome of breast cancer patients treated with radiofrequency ablation. European Journal of Surgical Oncology (EJSO). 2012;38(11):1036-42.
Tsuda H, Seki K, Hasebe T, Sasajima Y, Shibata T, Iwamoto E, et al. A histopathological study for evaluation of therapeutic effects of radiofrequency ablation in patients with breast cancer. Breast Cancer. 2011;18(1):24-32.
Yamamoto N, Fujimoto H, Nakamura R, Arai M, Yoshii A, Kaji S, et al. Pilot study of radiofrequency ablation therapy without surgical excision for T1 breast cancer: evaluation with MRI and vacuum-assisted core needle biopsy and safety management. Breast Cancer. 2011;18(1):3-9.
Yoshinaga Y, Enomoto Y, Fujimitsu R, Shimakura M, Nabeshima K, Iwasaki A. Image and pathological changes after radiofrequency ablation of invasive breast cancer: a pilot study of nonsurgical therapy of early breast cancer. World journal of surgery. 2013;37(2):356-63.
Bloom KJ, Dowlat K, Assad L. Pathologic changes after interstitial laser therapy of infiltrating breast carcinoma. The American journal of surgery. 2001;182(4):384-8.
Burak Jr WE, Agnese DM, Povoski SP, Yanssens TL, Bloom KJ, Wakely PE, et al. Radiofrequency ablation of invasive breast carcinoma followed by delayed surgical excision. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2003;98(7):1369-76.
Duan WR, Garner DS, Williams SD, Funckes‐Shippy CL, Spath IS, Blomme EA. Comparison of immunohistochemistry for activated caspase‐3 and cleaved cytokeratin 18 with the TUNEL method for quantification of apoptosis in histological sections of PC‐3 subcutaneous xenografts. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland. 2003;199(2):221-8.
Kreb D, Bosscha K, Ernst M, Rutten M, Jager G, Van Diest P, et al. Use of cytokeratin 8 immunohistochemistry for assessing cell death after radiofrequency ablation of breast cancers. Biotechnic & Histochemistry. 2011;86(6):404-12.
García-Tejedor A, Guma A, Soler T, Valdivieso A, Petit A, Contreras N, et al. Radiofrequency ablation followed by surgical excision versus lumpectomy for early stage breast cancer: a randomized phase II clinical trial. Radiology. 2018;289(2):317-24.
Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, et al. NCCN guidelines insights: breast cancer, version 1.2017. Journal of the National Comprehensive Cancer Network. 2017;15(4):433-51.
Simard ML, Mourier A, Greaves LC, Taylor RW, Stewart JB. A novel histochemistry assay to assess and quantify focal cytochrome c oxidase deficiency. The Journal of pathology. 2018;245(3):311-23.
Kabakov AE, Gabai VL. Cell death and survival assays. Chaperones: Springer; 2018. p. 107-27.
Singla K, Sandhu SV, Pal RA, Bansal H, Bhullar RK, Kaur P. Comparative evaluation of different histoprocessing methods. International journal of health sciences. 2017;11(2):28.
Oura S, Tamaki T, Hirai I, Yoshimasu T, Ohta F, Nakamura R, et al. Radiofrequency ablation therapy in patients with breast cancers two centimeters or less in size. Breast cancer. 2007;14(1):48-54.
Fornage BD, Sneige N, Ross MI, Mirza AN, Kuerer HM, Edeiken BS, et al. Small (≤ 2-cm) breast cancer treated with US-guided radiofrequency ablation: feasibility study. Radiology. 2004;231(1):215-24.
Kreb D, Looij B, Ernst M, Rutten M, Jager G, van der Linden J, et al. Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: lessons for further research. The Breast. 2013;22(4):543-7.
Motoyoshi A, Noguchi M, Earashi M, Zen Y, Fujii H. Histopathological and immunohistochemical evaluations of breast cancer treated with radiofrequency ablation. Journal of surgical oncology. 2010;102(5):385-91.
Ishizaka H, Ishijima H, Katsuya T, Koyama Y. Percutaneous ethanol injection therapy: use of a directable needle guide. American journal of roentgenology. 1997;168(6):1563-4.
Itoh T, Orba Y, Takei H, Ishida Y, Saitoh M, Nakamura H, et al. Immunohistochemical detection of hepatocellular carcinoma in the setting of ongoing necrosis after radiofrequency ablation. Modern pathology. 2002;15(2):110-5.
Lee JM, Park JH, Kim BY, Kim I-H. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay to characterize histopathologic changes following thermal injury. Annals of dermatology. 2018;30(1):41.
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