J Pathol Transl Med.  2022 Jul;56(4):199-204. 10.4132/jptm.2022.03.19.

Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma

• Na JM
• Kim DC
• Song DH
• An HJ
• Koh HM
• Lee JH
• Lee JS
• Yang JW
• Kim MH

• KMID: 2531611
• DOI: http://doi.org/10.4132/jptm.2022.03.19

Abstract

Background
Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis.
Methods
We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated.
Results
Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors.
Conclusions
Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

Keyword

Myoferlin; Papillary thyroid carcinoma; Lymph node metastasis; Tumor staging

Figure

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  Fig. 1 (A) Myoferlin expression observed in the cytoplasm and membrane of normal thyroid follicular cells. (B–E) Myoferlin expression observed in papillary thyroid carcinoma. Negative (B), weak (+1) (C), moderate (+2) (D), and strong (+3) (E) myoferlin expression in tumor cells.

Reference

References

1. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 [see commetns]. Cancer. 1998; 83:2638–48.

2. Amin MB, Edge S, Greene FL, et al. AJCC cancer staging manual. 8th ed. New York: Spinger;2017. p. 873–90.

3. Harwood J, Clark OH, Dunphy JE. Significance of lymph node metastasis in differentiated thyroid cancer. Am J Surg. 1978; 136:107–12.

4. Zaydfudim V, Feurer ID, Griffin MR, Phay JE. The impact of lymph node involvement on survival in patients with papillary and follicular thyroid carcinoma. Surgery. 2008; 144:1070–7.

5. Nixon IJ, Wang LY, Palmer FL, et al. The impact of nodal status on outcome in older patients with papillary thyroid cancer. Surgery. 2014; 156:137–46.

6. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26:1–133.

7. Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. A novel classification system for patients with PTC: addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow-up period. Surgery. 2004; 135:139–48.

8. Wang LY, Palmer FL, Nixon IJ, et al. Central lymph node characteristics predictive of outcome in patients with differentiated thyroid cancer. Thyroid. 2014; 24:1790–5.

9. Jeon MJ, Yoon JH, Han JM, et al. The prognostic value of the metastatic lymph node ratio and maximal metastatic tumor size in pathological N1a papillary thyroid carcinoma. Eur J Endocrinol. 2013; 168:219–25.

10. Lee J, Song Y, Soh EY. Prognostic significance of the number of metastatic lymph nodes to stratify the risk of recurrence. World J Surg. 2014; 38:858–62.

11. Doherty KR, Cave A, Davis DB, et al. Normal myoblast fusion requires myoferlin. Development. 2005; 132:5565–75.

12. Demonbreun AR, Posey AD, Heretis K, et al. Myoferlin is required for insulin-like growth factor response and muscle growth. FASEB J. 2010; 24:1284–95.

13. Leung C, Yu C, Lin MI, Tognon C, Bernatchez P. Expression of myoferlin in human and murine carcinoma tumors: role in membrane repair, cell proliferation, and tumorigenesis. Am J Pathol. 2013; 182:1900–9.

14. Volakis LI, Li R, Ackerman WEt, et al. Loss of myoferlin redirects breast cancer cell motility towards collective migration. PLoS One. 2014; 9:e86110.

15. Li R, Ackerman WEt, Mihai C, Volakis LI, Ghadiali S, Kniss DA. Myoferlin depletion in breast cancer cells promotes mesenchymal to epithelial shape change and stalls invasion. PLoS One. 2012; 7:e39766.

16. Song DH, Ko GH, Lee JH, et al. Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression. Oncol Lett. 2016; 11:998–1006.

17. Wang WS, Liu XH, Liu LX, et al. iTRAQ-based quantitative proteomics reveals myoferlin as a novel prognostic predictor in pancreatic adenocarcinoma. J Proteomics. 2013; 91:453–65.

18. Song DH, Ko GH, Lee JH, et al. Prognostic role of myoferlin expression in patients with clear cell renal cell carcinoma. Oncotarget. 2017; 8:89033–9.

19. Hermanns C, Hampl V, Holzer K, et al. The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma. Oncogene. 2017; 36:3464–76.

20. Kim MH, Song DH, Ko GH, et al. Myoferlin expression and its correlation with FIGO histologic grading in early-stage endometrioid carcinoma. J Pathol Transl Med. 2018; 52:93–7.

21. Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics: tissue-based map of the human proteome. Science. 2015; 347:1260419.