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HOME > Kosin Med J > Volume 30(2); 2015 > Article
Original Article
Analysis of an EGFR mutation by PNA clamping method in lung carcinoid tumors
Jong In Kim
Kosin Medical Journal 2015;30(2):141-147.
DOI: https://doi.org/10.7180/kmj.2015.30.2.141
Published online: January 20, 2015

Department of Thoracic and Cardiovascular Surgery, College of Medicine, Kosin University, Busan, Korea.

Corresponding Author: Jong In Kim, Department of Thoracic and Cardiovascular Surgery, College of Medicine, Kosin University, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea. TEL: +82-51-990-6253 FAX: +82-51-990-3994 E-mail: schoi@ns.kosinmed.or.kr
• Received: October 21, 2014   • Accepted: April 1, 2015

Copyright © 2015 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background
    Pulmonary carcinoid tumors consisting of typical carcinoid tumors (TC) and atypical carcinoid tumors (AC) are rare, accounting for 2–5% of all lung tumors. TC is considered a low-grade tumor with a rate of distant metastasis up to 12%. In contrast, ACs are more aggressive tumors, displaying a metastatic rate up to 70%. Surgery is the treatment of choice; however, the current treatment outcomes of metastatic lung carcinoids are discouraging. This study aimed to investigate the EGFR mutation using the PNA-mediated clamping method and to provide basic data for using EGFR-TK1 and its clinical implications.
  • Materials and Methods
    A total of 14 cases that underwent surgery were diagnosed as carcinoid tumors and pathologically classified as TC and AC. The paraffin-embedded tissues were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. The mutant type was noted in the cases with aCt greater than 2.0.
  • Result
    Of 14 cases, eight were AC and six cases were TC. No known EGFR mutation was detected with aCt less than 2.0.
  • Conclusion
    The EGFR genotype determined using the PNA-mediated PCR clamping method was wild-type in all pulmonary carcinoid tumors. Therefore, the application of EGFR-TK1 is limited in pulmonary carcinoid tumors.
Fig. 1.
The four steps of the PCR cycle in PNA ClampTM
kmj-30-141f1.jpg
Fig. 2.
The wild type was detected in PNA-mediated clamping real-time PCR for EGFR.
kmj-30-141f2.jpg
Table 1.
The clinical and pathological characteristics of 14 cases of pulmonary carcinoid tumors
Case Dx Age Gender Tumor Size (cm) No of mitosis events (/10HPF) Necrosis Lymph node metastasis Neuroendocrine markers
1 T 63 F 2.8 0 +
2 T 41 F 3 1 +
3 T 48 M 5 0 +
4 T 53 M 3.5 1 +
5 T 31 M 1.8 0 +
6 T 59 M 1.2 0 +/-
7 A 34 M 4 6 +
8 A 55 M 5 7 + +
9 A 47 M 4.8 5 +
10 A 61 M 4.5 10 + +
11 A 54 M 3.3 4 + +
12 A 72 M 5 4 + +
13 A 62 M 2.3 3 +
14 A 57 M 0.5 5 +

A: atypical carcinoid, T: typical carcinoid, M: male, F: female, +: present, -: absent

Table 2.
The results of analysis of EGFR PNA-mediated clamping using real-time PCR
Sample No(Ct) G719X (①) E19 del. (②) T790M (③) S768I (④) Ins. 3 dup (⑤) Ins.3 (⑥) L858R & L861Q(⑦) Non-PNA (⑧)
15 39.11 38 38 33.24 39.02 36.5 38 28.63
Clamping control 38 36.16 39.79 31.82 30.42 35.92 34.42 23.66
standard Ct 36 33 33 30 27 30 33  
△Ct –2 –0.06 –0.37 –3.91 –3.45 –8 –6.62  
determine wild wild wild wild wild wild Wild  

Criterion: EGFR mutation is noted when the △Ct value, standard Ct minus sample Ct, is 2.0 or above. [△Ct = standard ct – sample ct]

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