J Korean Soc Radiol.  2020 Jan;81(1):147-156. 10.3348/jksr.2020.81.1.147.

Diagnostic Value of CYFRA 21-1 Measurement in Fine-Needle Aspiration Washouts for Detection of Axillary Recurrence in Postoperative Breast Cancer Patients

• Won SY
• Kim EK
• Moon HJ
• Yoon JH
• Park VY
• Kim MJ

• KMID: 2469188
• DOI: http://doi.org/10.3348/jksr.2020.81.1.147

Abstract

PURPOSE
The objective of this study was to evaluate the diagnostic value and threshold levels of cytokeratin fragment 21-1 (CYFRA 21-1) in fine-needle aspiration (FNA) washouts for detection of lymph node (LN) recurrence in postoperative breast cancer patients.
MATERIALS AND METHODS
FNA cytological assessments and CYFRA 21-1 measurement in FNA washouts were performed for 64 axillary LNs suspicious for recurrence in 64 post-operative breast cancer patients. Final diagnosis was made on the basis of FNA cytology and follow-up data over at least 2 years. The concentration of CYFRA 21-1 was compared between recurrent LNs and benign LNs. Diagnostic performance and cut-off value were evaluated using a receiver operating characteristic curve.
RESULTS
Regardless of the non-diagnostic results, the median concentration of CYFRA 21-1 in recurrent LNs was significantly higher than that in benign LNs (p < 0.001). The optimal diagnostic cut-off value was 1.6 ng/mL. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CYFRA 21-1 for LN recurrence were 90.9%, 100%, 100%, 98.1%, and 98.4%, respectively.
CONCLUSION
Measurement of CYFRA 21-1 concentration from ultrasound-guided FNA biopsy aspirates showed excellent diagnostic performance with a cut-off value of 1.6 ng/mL. These results indicate that measurement of CYFRA 21-1 concentration in FNA washouts is useful for the diagnosis of axillary LN recurrence in post-operative breast cancer patients.

MeSH Terms

Biopsy
Biopsy, Fine-Needle*
Breast Neoplasms*
Breast*
Diagnosis
Follow-Up Studies
Humans
Keratins
Lymph Nodes
Postoperative Period
Recurrence*
ROC Curve
Sensitivity and Specificity
Keratins

Figure

• 

  Fig. 1 Concentration of CYFRA 21-1 in FNA washouts from benign and recurrent axillary lymph nodes. CYFRA 21-1 = cytokeratin fragment 21-1, FNA = fine-needle aspiration

• 

  Fig. 2 ROC curve of CYFRA 21-1 concentration for detecting recurrent axillary LNs when LNs with non-diagnostic results (n = 12) in fine-needle aspiration were considered as benign LNs. CYFRA 21-1 = cytokeratin fragment 21-1, LN = lymph node, ROC = receiver operating characteristics curve

Reference

1. Cools-Lartigue J, Meterissian S. Accuracy of axillary ultrasound in the diagnosis of nodal metastasis in invasive breast cancer: a review. World J Surg. 2012; 36:46–54.

2. Jain A, Haisfield-Wolfe ME, Lange J, Ahuja N, Khouri N, Tsangaris T, et al. The role of ultrasound-guided fineneedle aspiration of axillary nodes in the staging of breast cancer. Ann Surg Oncol. 2008; 15:462–471.

3. Park SH, Kim MJ, Park BW, Moon HJ, Kwak JY, Kim EK. Impact of preoperative ultrasonography and fine-needle aspiration of axillary lymph nodes on surgical management of primary breast cancer. Ann Surg Oncol. 2011; 18:738–744.

4. Van Rijk MC, Deurloo EE, Nieweg OE, Gilhuijs KG, Peterse JL, Rutgers EJ, et al. Ultrasonography and fine-needle aspiration cytology can spare breast cancer patients unnecessary sentinel lymph node biopsy. Ann Surg Oncol. 2006; 13:31–35.

5. Koelliker SL, Chung MA, Mainiero MB, Steinhoff MM, Cady B. Axillary lymph nodes: US-guided fine-needle aspiration for initial staging of breast cancer--correlation with primary tumor size. Radiology. 2008; 246:81–89.

6. Deurloo EE, Tanis PJ, Gilhuijs KG, Muller SH, Kröger R, Peterse JL, et al. Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer. Eur J Cancer. 2003; 39:1068–1073.

7. Choi JS, Kim MJ, Moon HJ, Kim EK, Yoon JH. False negative results of preoperative axillary ultrasound in patients with invasive breast cancer: correlations with clinicopathologic findings. Ultrasound Med Biol. 2012; 38:1881–1886.

8. Kim MJ, Park BW, Lim JB, Kim HS, Kwak JY, Kim SJ, et al. Axillary lymph node metastasis: CA-15-3 and carcinoembryonic antigen concentrations in fine-needle aspirates for preoperative diagnosis in patients with breast cancer. Radiology. 2010; 254:691–697.

9. Yoon JH, Han KH, Kim EK, Moon HJ, Kim MJ, Suh YJ, et al. Fine-needle aspirates CYFRA 21-1 is a useful tumor marker for detecting axillary lymph node metastasis in breast cancer patients. PLoS One. 2013; 8:e57248.

10. Choi JS, Han KH, Kim EK, Moon HJ, Yoon JH, Kim MJ. Fine-needle aspirate CYFRA 21-1, an innovative new marker for diagnosis of axillary lymph node metastasis in breast cancer patients. Medicine (Baltimore). 2015; 94:e811.

11. Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007; 13:4807–4816.

12. Nakata B, Ogawa Y, Ishikawa T, Ikeda K, Kato Y, Nishino H, et al. Serum CYFRA 21-1 is one of the most reliable tumor markers for breast carcinoma. Cancer. 2000; 89:1285–1290.

13. Nakata B, Takashima T, Ogawa Y, Ishikawa T, Hirakawa K. Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer. Br J Cancer. 2004; 91:873–878.

14. Lu WL, Jansen L, Post WJ, Bonnema J, Van de Velde JC, De Bock GH. Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer: a meta-analysis. Breast Cancer Res Treat. 2009; 114:403–412.

15. Galper S, Recht A, Silver B, Manola J, Gelman R, Schnitt SJ, et al. Factors associated with regional nodal failure in patients with early stage breast cancer with 0-3 positive axillary nodes following tangential irradiation alone. Int J Radiat Oncol Biol Phys. 1999; 45:1157–1166.

16. Harris EE, Hwang WT, Seyednejad F, Solin LJ. Prognosis after regional lymph node recurrence in patients with stage I-II breast carcinoma treated with breast conservation therapy. Cancer. 2003; 98:2144–2151.

17. Fisher B, Bauer M, Margolese R, Poisson R, Pilch Y, Redmond C, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985; 312:665–673.

18. Leung S, Otmezguine Y, Calitchi E, Mazeron JJ, Le Bourgeois JP, Pierquin B. Locoregional recurrences following radical external beam irradiation and interstitial implantation for operable breast cancer--a twenty three year experience. Radiother Oncol. 1986; 5:1–10.

19. Pierquin B, Mazeron JJ, Glaubiger D. Conservative treatment of breast cancer in Europe: report of the Groupe Européen de Curiethérapie. Radiother Oncol. 1986; 6:187–198.

20. Kauczor HU, Voges EM, Wieland-Schneider C, Mitze M, Thelen M. Value of routine abdominal and lymph node sonography in the follow-up of breast cancer patients. Eur J Radiol. 1994; 18:104–108.

21. Dian D, Straub J, Scholz C, Mylonas I, Rack B, Sommer H, et al. Influencing factors for regional lymph node recurrence of breast cancer. Arch Gynecol Obstet. 2008; 277:127–134.

22. Hammon M, Dankerl P, Janka R, Wachter DL, Hartmann A, Schulz-Wendtland R, et al. Fine needle aspiration cytology of lymph nodes in breast cancer follow-up is a feasible alternative to watchful waiting and to histology. BMC Womens Health. 2015; 15:114.

23. Alvarenga CA, Paravidino PI, Alvarenga M, Dufloth R, Gomes M, Zeferino LC, et al. Expression of CK19 in invasive breast carcinomas of special histological types: implications for the use of one-step nucleic acid amplification. J Clin Pathol. 2011; 64:493–497.

24. Molina R, Agusti C, Filella X, Jo J, Joseph J, Giménez N, et al. Study of a new tumor marker, CYFRA 21-1, in malignant and nonmalignant diseases. Tumour Biol. 1994; 15:318–325.

25. Suh YJ, Kim MJ, Kim J, Yoon JH, Moon HJ, Kim EK. Tumor markers in fine-needle aspiration washout for cervical lymphadenopathy in patients with known malignancy: preliminary study. AJR Am J Roentgenol. 2011; 197:W730–W736.