Skip to main content
  • Research note
  • Open access
  • Published:

High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia



Thyroid cancer incidence has steadily increased in Indonesia. However, data on Kirsten rat sarcoma virus (KRAS) and EGFR mutations in thyroid cancer in Indonesia remain unavailable, except for BRAF-V600E, the most common BRAF gene mutation. This study aimed to analyze KRAS and EGFR mutation profiles in BRAF-V600E negative thyroid cancer samples.


BRAF-V600E mutations were found in papillary thyroid carcinomas in 40.3% patients with mean age of 53 years old. In BRAF-V600E-negative samples, 41.3% had KRAS mutations with mean age of 55.5 years old. KRAS mutation was found in 52.6% of follicular carcinomas and 47.4% of papillary thyroid carcinomas. Additionally, 45.7% had EGFR mutations in patients with mean age of 50.5 years old. EGFR mutation was found in 71.4% of papillary thyroid carcinoma and 28.6% of follicular carcinoma. Nearly half of the BRAF-V600E negative thyroid carcinoma samples harbored either KRAS or EGFR mutations. This finding suggests that in BRAF-V600E negative thyroid carcinoma samples, testing for RAS and EGFR mutation may be warranted for further therapeutic consideration.


Thyroid cancer is the most common endocrine cancer in the world, with Indonesia ranked 9th position in 2010 [1, 2]. The currently available prognostic factors in thyroid cancer are the TNM classification of malignant tumors (TNM) staging, age, gender, and histopathology profile (including capsular invasion and angioinvasion) [3]. Although clinical assessment of these factors are known, the frequency and behavior of thyroid cancer vary greatly, ranging from frequent and generally asymptomatic to larger and more advanced papillary tumors.

Mutation in B-Raf proto-oncogene (BRAF) is the gene most often disrupted in thyroid cancer [4]. BRAF-V600E mutation increases disease progression risk in thyroid cancer and correlates with poor prognosis [5, 6]. Following BRAF mutations, Ras proteins are related to follicular-patterned neoplasms and are the second most common genetic alteration seen in thyroid carcinomas [7]. The RAS proteins are encoded by three human RAS genes: Kirsten rat sarcoma viral (KRAS), neuroblastoma (NRAS) and Harvey (HRAS). However, despite extensive research, their profile remains largely uncharacterized especially in Indonesia [8]. Epidermal growth factor receptor (EGFR), on the other hand, have been implicated in various cancer pathogenesis, including thyroid cancer [9, 10]. EGFR was also implied to be important for thyroid carcinoma proliferation and metastasis, and high EGFR level was reported in malignant thyroid cancer with wild type BRAF [10,11,12]. This suggest that EGFR mutation profile in thyroid cancer should not be overlooked. Overall, investigation for different mutation profiles on thyroid carcinomas is still required to understand the key mutation that occurred.

With high mutation prevalence in thyroid cancer, a preoperative approach is required to assist clinicians in determining the extent to which surgical intervention and adjuvant therapy are required. However, research focusing on mutation profile, including the presence of KRAS and EGFR mutations in addition to BRAF mutations in thyroid cancer, is still rarely described, particularly in Indonesia. This study is expected to be a reference in making diagnostic and treatment decisions in thyroid cancer.

Main text

Materials and methods

Study design

This study was an retrospective observational study design. Samples were obtained from the archive between 2013 and 2019 and used to investigate BRAF, KRAS, and EGFR mutations in thyroid carcinoma samples. Paraffin blocks from patients histopathologically diagnosed with primary thyroid carcinoma (papillary thyroid carcinoma of all variants, and follicular thyroid carcinoma) were included. Samples were obtained from Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, and CITO Pathology Laboratory. Histological evaluation was reviewed by two pathologists and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) samples were excluded. The paraffin blocks were required to contain more than 50% area of tumor. Exclusion criteria were damaged paraffin blocks and paraffin blocks stored at temperatures other than room temperature. This study initially collected 87 primary thyroid carcinoma cases. Of those, highly degraded DNA samples were excluded, leaving only 77 paraffin blocks meeting the criteria. The samples were then examined for BRAF, KRAS and EGFR mutation at Department of Anatomical Pathology; Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada. All specimens were collected under approval of ethical committee at Medical and Health Research Ethics Committee (MHREC) Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada-Dr. Sardjito General Hospital (Ref. No.: KE/FK/0411/EC/2020).

DNA extraction

DNA extraction was performed from paraffin blocks using tissue genomic DNA mini kit (GeneAll® Clinic SV mini Cat. 108-101, Seoul, Korea) according to the manufacturer’s instructions.

Real-time polymerase chain reaction (qRT-PCR)

DNA samples were assayed using AmoyDx BRAF-V600 mutation detection kit (Amoy Diagnostics, Xiamen, China) [13]; AmoyDx human EGFR gene mutations fluorescence PCR diagnostic kit (Amoy Diagnostics, Xiamen, China), detecting T970M, L858R, L861Q, S7681, G719S, G719A, G719C, 3 insertions in exon 20, and 19 deletions in exon 19 [14]; and AmoyDx KRAS Mutations Detection Kit (Amoy Diagnostics, Xiamen, China) [15]. Quantitative PCR was performed using Bioneer Exicycler™ 96 Real-Time Quantitative Thermal Block. The assays and PCR condition were as manufacturer’s recommendation. Briefly, region of interest within the DNA sequence is amplified using the polymerase chain reaction, in which the DNA of the mutant gene is amplified by specific primers and detected by novel probes. The amplified region of interest is heated gradually until the double stranded DNA breaks. The cycle threshold (Ct) values at which the signal is detected above the fluorescence background of the respective mutation testing kit were used to determine whether a sample is positive or negative. Internal control reagents are intended to detect the presence of inhibitors, which can result in false-negative results. The real-time PCR was performed with 1 cycle denaturation at 95 °C for 5 min, 15 cycles annealing at 95 °C for 25 s, 64 °C for 20 s, and 72 °C for 20 s, and 31 cycles extension at 93 °C for 25 s, 60 °C for 35 s, and 72 °C for 20 s.

Data analysis

All data presented were made using Microsoft Excel 2020 for Mac OSX. Categorical data were expressed as frequency and percentage, and quantitative data were expressed as mean.


Clinicopathologic characteristics of the thyroid carcinoma samples

Characteristics of the samples are shown in Table 1. A total of 37 (48.1%) samples were from males and 40 (51.9%) samples were from females. The mean age of the patients was 53.6 ± 13.4 years old. The histopathological types were 57 samples of papillary type (74%) and 20 samples of follicular type (26%). The papillary type was consisted of 32 classic variant (56.1%), 19 follicular variant (33.3%), and three samples of tall cell and columnar cells variant (5.3% and 5.3%, respectively).

Table 1 Characteristics of the study samples

BRAF-V600E mutation status in thyroid carcinoma samples

A total of 31 (40.3%) samples showed BRAF positive mutation consisted of 5 males and 26 females (Table 2). The mean age of the patients was 53.0 ± 14.7 years old. Histopathological types of BRAF positive mutation samples were of papillary type, with classic variant of 26 samples (76.5%) and follicular of 5 (14.7%) samples.

Table 2 Characteristics and BRAF-V600E mutation status in thyroid carcinoma samples

KRAS and EGFR mutation were detected in BRAF-V600E negative samples

Further examination of the BRAF-negative samples revealed that 19 (41.3%) were KRAS positive, with 15 of males and 4 of females (Table 3). The mean age was 55.5 ± 12.4 years old. Histopathological types of KRAS positive mutation samples were of papillary type 9 (47.4%) samples and follicular type 10 (52.6%) samples. The papillary type consisted of two (10.5%) classic variant samples, three (15.8%) follicular samples, three (15.8%) tall cell samples, and one (5.2%) columnar cell variant. Capsular invasion was observed in 84.2% of KRAS positive samples, while vascular invasion was observed in 78.9% of samples.

Table 3 Characteristics and mutation status of KRAS and EGFR in BRAF-V600E negative thyroid carcinoma samples

BRAF negative samples also showed EGFR positive mutation in 21 (45.7%) samples consisted of 13 males and 8 female samples. The mean age was 50.5 ± 12.5 years old. Histopathological types of EGFR positive samples were 15 papillary type (71.4%), and six follicular type (28.6%). The papillary type consisted of four classic variant samples (19%), nine follicular (42.9%) samples, and two (9.5%) columnar cell variants. Capsular invasion was found in 81.0% of EGFR positive samples, with vascular invasion in 57.1% of the samples. Notably we also identified one papillary thyroid carcinoma of follicular variant with both KRAS and EGFR mutation (Additional file 1: Table S2).


The main findings of this study were (1) The thyroid cancers samples were consisted of papillary type carcinoma (74.0%) and follicular type carcinoma (26.0%), (2) BRAF-V600E mutation were found in 40.3% of thyroid carcinoma samples, (3) KRAS mutation was found in 41.3% of BRAF negative thyroid carcinoma samples, with predominant follicular type, and (4) EGFR mutation was observed in 45.7% of BRAF negative thyroid carcinoma samples, with predominant papillary type.

We observed that thyroid cancers samples were mainly of papillary type. Papillary thyroid carcinoma was the most common carcinoma arising from the thyroid gland [16]. In South Korea, for example, papillary thyroid carcinoma accounted for the greatest age-standardized incidence rate [16]. Even though it is considered as malignancy with good prognosis, recent study with 15-year median follow up showed significantly lower survival percentage in papillary thyroid carcinoma with BRAF mutation [17]. Therefore, determining the thyroid carcinoma mutation profile is important in determining patient prognosis.

We observed that BRAF mutation was found in 40.3% of all thyroid samples, which is comparable to previous studies in Southeast Asia. Previous study in Philippine reported 38.46% of BRAF mutation identified in thyroid samples [18]. Another study in Hanoi showed that 56.3% of all thyroid samples have BRAF mutation [19]. These findings, along with the prognostic value of BRAF mutation, may have contributed the high thyroid cancer deaths (3103 deaths) in Indonesia, despite that papillary thyroid cancer had good survival rate [20]. The number of deaths came at third position following China and India. BRAF mutations were associated with thyroid cancer pathogenesis, leading to unregulated cell growth and carcinogenesis as well as extrathyroidal extension and advanced stage [18, 21]. This implies that identifying mutations in thyroid cancer is critical for better diagnosis and, potentially, better treatment.

The RAS proteins transmit extracellular signals that promote cell proliferation, differentiation, and survival [22, 23]. The EGFR signaling plays a role in signaling the downstream BRAF. Therefore, we conduct testing on KRAS and EGFR mutation in thyroid cancer patients who did not harbor BRAF mutation. We observed that KRAS mutation occurred in 41.3% of the BRAF negative thyroid cancer samples, and 52.6% of it was found in follicular thyroid carcinoma. Similar finding was reported in Japan in which 57% of follicular carcinomas harbored RAS mutations [8]. Another study in Saudi Arabia assessing proliferative thyroid lesions reported that 32% of mutations affected the KRAS codon 61 [24]. Consistently, we reported high KRAS prevalence and this may be higher since we reported KRAS mutations only in BRAF-negative thyroid cancer samples. Point mutations in the RAS or BRAF proto-oncogenes were detected in almost 70% of papillary thyroid carcinomas in nearly mutually exclusive manner [25]. This further shows that BRAF-negative samples are prone to have other mutations, including RAS mutations. In addition, this could be the factor contributing to poor prognosis in follicular thyroid carcinoma, as RAS mutation is linked to significant lower outcome [26]. Therefore, establishing the necessary mutation testing steps in thyroid carcinoma is important to determine the need for early intervention.

We also observed that 45.7% of BRAF negative thyroid carcinoma samples had EGFR mutation, with 71.4% was found in papillary thyroid carcinoma. This finding is similar to a study in United States with most of EGFR mutation was found in papillary thyroid carcinoma (46.2%), followed by follicular type (29.6%) [27]. EGFR is important for extracellular signal transduction from the surface into cells to mediate cell proliferation and apoptosis [27]. Its overexpression is common in breast, lung, and bladder cancer. Fisher et al. found that EGFR mutations correlates with advanced stage and lymph node metastases which may contribute to papillary thyroid carcinoma aggressiveness [27]. These suggest that EGFR mutation profile in thyroid carcinoma should not be excluded.

Interestingly, coexistence mutations (both KRAS and EGFR mutations) were found in 1 of our BRAF negative thyroid carcinoma sample. In non-small cell lung cancer (NSCLC), for example, coexistence mutations of KRAS and EGFR are relatively rare [28]. This phenomenon was suggested to occur due to heterogeneity in malignant cells where some subpopulations of the cells had different mutations. The EGFR coexistence with KRAS mutation resulted in significantly shorter progression free survival [29]. Although KRAS and EGFR mutations have been well investigated in NSCLC, however, study of these mutations on thyroid carcinoma is still limited. These findings emphasize the importance of identifying KRAS and EGFR mutations following the most common genetic alteration in thyroid cancer, BRAF.

Our study highlights the frequent BRAF, KRAS, and EGFR mutations in thyroid carcinomas. Of those BRAF-V600E negative samples, almost half had either KRAS or EGFR mutations. Although differentiated thyroid cancers have favourable prognosis, about 30% will experience recurrent disease after 10 years [30]. BRAF, KRAS, and EGFR mutations in recurrent thyroid cancer may benefit from targeted therapies and further study on these mutations with their risk of recurrence, distant metastasis, and overall prognosis in thyroid cancers may be required.


We discovered that either KRAS or EGFR mutations can be found in nearly half of the BRAF negative thyroid carcinoma samples. Thyroid carcinoma-related death is still a burden in Indonesia. These findings suggest that additional mutational pathways, such as KRAS and EGFR, should be tested in BRAF-V600E negative thyroid carcinoma samples. The breakthrough in molecular testing guidelines might provide help in determining the prognosis of thyroid cancer and might aid clinicians in determining early intervention for better outcome.


Due to sample availability, this study only comprised a small number of specimens. In addition, the data obtained in this study were pathology data, whereas with clinical and survival data, a better association can be concluded. Future research should have a large enough sample size to establish enough statistical power for analysis.

Availability of data and materials

All data generated or analysed during this study are included in this published article.



B-Raf proto-oncogene serine/threonine kinase


Epidermal growth factor receptor


Kirsten rat sarcoma virus


Non-small cell lung cancer


Real-time polymerase chain reaction


Tyrosine kinase inhibitor


TNM classification of malignant tumors


  1. La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F, Negri E. Thyroid cancer mortality and incidence: a global overview. Int J Cancer. 2015;136(9):2187–95.

    Article  Google Scholar 

  2. Fitriyani H, Alferraly TI, Laksmi LI. Correlation between Tsh, T3, T4 and histological types of thyroid carcinoma. Indones J Clin Pathol Med Lab. 2018;24(3):201–4.

    Article  Google Scholar 

  3. Konturek A, Barczyński M, Nowak W, Richter P. Prognostic factors in differentiated thyroid cancer—a 20-year surgical outcome study. Langenbeck’s Arch Surg. 2012;397(5):809–15.

    Article  Google Scholar 

  4. Xing M, Condouris S, Liu Z, Liu D. BRAF V600E maintains proliferation, transformation, and tumorigenicity of BRAF-mutant papillary thyroid cancer cells. J Clin Endocrinol Metab. 2007;92(6):2264–71.

    Article  Google Scholar 

  5. Knauf JA, Ma X, Smith EP, Zhang L, Mitsutake N, Liao X-H, Refetoff S, Nikiforov YE, Fagin JA. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005;65(10):4238–45.

    Article  CAS  Google Scholar 

  6. Mesa C, Mirza M, Mitsutake N, Sartor M, Medvedovic M, Tomlinson C, Knauf JA, Weber GF, Fagin JA. Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling. Cancer Res. 2006;66(13):6521–9.

    Article  CAS  Google Scholar 

  7. Howell GM, Hodak SP, Yip L. RAS mutations in thyroid Cancer. Oncologist. 2013;18(8):926–32.

    Article  CAS  Google Scholar 

  8. Fukahori M, Yoshida A, Hayashi H, Yoshihara M, Matsukuma S, Sakuma Y, Koizume S, Okamoto N, Kondo T, Masuda M, et al. The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012;22(7):683–9.

    Article  CAS  Google Scholar 

  9. Hu Z, Zou X, Qin S, Li Y, Wang H, Yu H, Sun S, Wu X, Wang J, Chang J. Hormone receptor expression correlates with EGFR gene mutation in lung cancer in patients with simultaneous primary breast cancer. Transl Lung Cancer Res. 2020;9(2):325–36.

    Article  CAS  Google Scholar 

  10. Janković J, Tatić S, Božić V, Živaljević V, Cvejić D, Paskaš S. Inverse expression of caveolin-1 and EGFR in thyroid cancer patients. Hum Pathol. 2017;61:164–72.

    Article  Google Scholar 

  11. Schiff BA, McMurphy AB, Jasser SA, Younes MN, Doan D, Yigitbasi OG, Kim S, Zhou G, Mandal M, Bekele BN, et al. Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer. Clin Cancer Res. 2004;10(24):8594–602.

    Article  CAS  Google Scholar 

  12. Lote H, Bhosle J, Thway K, Newbold K, O’Brien M. Epidermal growth factor mutation as a diagnostic and therapeutic target in metastatic poorly differentiated thyroid carcinoma: a case report and review of the literature. Case Rep Oncol. 2014;7(2):393–400.

    Article  Google Scholar 

  13. Sheng L, Shi J, Han B, Lv B, Li L, Chen B, Liu N, Cao Y, Turner AG, Zeng Q. Predicting factors for central or lateral lymph node metastasis in conventional papillary thyroid microcarcinoma. Am J Surg. 2020;220(2):334–40.

    Article  Google Scholar 

  14. Liu Y, Wu S, Zhou L, Guo Y, Zeng X. Pitfalls in RET fusion detection using break-apart FISH probes in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2021;106(4):e1129-38.

    Article  Google Scholar 

  15. Souglakos J, Chat-Uthai N, Vejvisithsakul P, Udommethaporn S, Meesiri P, Danthanawanit C, Wongchai Y, Teerapakpinyo C, Shuangshoti S, Poungvarin N. Development of ultra-short PCR assay to reveal BRAF V600 mutation status in Thai colorectal cancer tissues. PLoS ONE. 2018;13(6):e0198795.

    Article  Google Scholar 

  16. Miranda-Filho A, Lortet-Tieulent J, Bray F, Cao B, Franceschi S, Vaccarella S, Dal Maso L. Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol. 2021;9(4):225–34.

    Article  Google Scholar 

  17. Elisei R, Ugolini C, Viola D, Lupi C, Biagini A, Giannini R, Romei C, Miccoli P, Pinchera A, Basolo F. BRAFV600E mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab. 2008;93(10):3943–9.

    Article  CAS  Google Scholar 

  18. Navarro-Locsin CG, Chang AM, Daroy ML, Alfon AC, Andal JJ, Padua PF. Clinical and histopathological profile of BRAF V600E mutation in conventional papillary thyroid carcinoma in a filipino population. Malays J Pathol. 2016;38(2):141–8.

    CAS  Google Scholar 

  19. Tran TV, Dang KX, Pham QH, Nguyen UD, Trinh NTT, Hoang LV, Ho SA, Nguyen BV, Nguyen DT, Trinh DT, et al. Evaluation of the expression levels of BRAFV600E mRNA in primary tumors of thyroid cancer using an ultrasensitive mutation assay. BMC Cancer. 2020;20(1):368.

    Article  CAS  Google Scholar 

  20. Salehiniya H, Pakzad R, Hassanipour S, Mohammadian M. The incidence and mortality of thyroid cancer and its relationship with HDI in the world. World Cancer Res J. 2018;5(2):1–6.

    Google Scholar 

  21. Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, Elisei R, Bendlová B, Yip L, Mian C, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015;33(1):42–50.

    Article  Google Scholar 

  22. Özdamar O, Acar G, Özen F, ZengİNkİNet T. Assessment of BRAF V600E, KRAS, NRAS and EGFR mutations in papillary thyroid carcinoma and Hashimoto Thyroiditis. ENT Updates. 2020;10:300–5.

    Google Scholar 

  23. Prior IA, Lewis PD, Mattos C. A comprehensive survey of ras mutations in cancer. Cancer Res. 2012;72(10):2457–67.

    Article  CAS  Google Scholar 

  24. Schulten HJ, Salama S, Al-Ahmadi A, Al-Mansouri Z, Mirza Z, Al-Ghamdi K, Al-Hamour OA, Huwait E, Gari M, Al-Qahtani MH, et al. Comprehensive survey of HRAS, KRAS, and NRAS mutations in proliferative thyroid lesions from an ethnically diverse population. Anticancer Res. 2013;33(11):4779–84.

    CAS  Google Scholar 

  25. Prete A, Borges de Souza P, Censi S, Muzza M, Nucci N, Sponziello M. Update on fundamental mechanisms of thyroid cancer. Front Endocrinol. 2020;11:102.

    Article  Google Scholar 

  26. Radkay LA, Chiosea SI, Seethala RR, Hodak SP, LeBeau SO, Yip L, McCoy KL, Carty SE, Schoedel KE, Nikiforova MN, et al. Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics. Cancer Cytopathol. 2014;122(12):873–82.

    Article  CAS  Google Scholar 

  27. Fisher KE, Jani JC, Fisher SB, Foulks C, Hill CE, Weber CJ, Cohen C, Sharma J. Epidermal growth factor receptor overexpression is a marker for adverse pathologic features in papillary thyroid carcinoma. J Surg Res. 2013;185(1):217–24.

    Article  CAS  Google Scholar 

  28. Lee T, Lee B, Choi Y-L, Han J, Ahn M-J, Um S-W. Non-small cell lung cancer with concomitant EGFR, KRAS, and ALK mutation: clinicopathologic features of 12 cases. J Pathol Transl Med. 2016;50(3):197–203.

    Article  Google Scholar 

  29. Rachiglio A, Fenizia F, Piccirillo M, Galetta D, Crinò L, Vincenzi B, Barletta E, Pinto C, Ferraù F, Lambiase M, et al. The presence of concomitant mutations affects the activity of EGFR tyrosine kinase inhibitors in EGFR-mutant Non-Small Cell Lung Cancer (NSCLC) patients. Cancers. 2019;11(3):341.

    Article  CAS  Google Scholar 

  30. Liu FH, Kuo SF, Hsueh C, Chao TC, Lin JD. Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis. J Surg Oncol. 2015;112(2):149–54.

    Article  Google Scholar 

Download references


The authors wish to thank Nur Eka Wiraditya and Vincent Lau, M.D. for technical support. Some parts of the data were extracted from the graduation thesis of Himawan Adhitama, M.D., Andreas Avellini Khrisnaputra Tandelilin, M.D., Ph.D., and Adrian Dewata Wardhana, M.D. in Universitas Gadjah Mada.


The authors received no financial support for the research, authorship, and publication of this article.

Author information

Authors and Affiliations



DSH, FSY: conceptualization, methodology. DSH, VL, WPA: data curation, writing-original draft preparation. VL, NVL, FSY: visualization, investigation. DSH, FSY, SLA: supervision. DSH, NVL, WPA: software, validation. DSH, SLA: writing-reviewing and editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Didik Setyo Heriyanto.

Ethics declarations

Ethics approval and consent to participate

This study was performed under the approval of the ethical committee at the Medical and Health Research Ethics Committee (MHREC) Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada-Dr. Sardjito General Hospital (Ref. No.: KE/FK/0411/EC/2020). All methods were carried out with the written informed consent in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

List of study samples. Table S2. KRAS and EGFR mutation status in BRAF-V600E negative samples.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heriyanto, D.S., Laiman, V., Limantara, N.V. et al. High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia. BMC Res Notes 15, 369 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: