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Clinicopathologic features and KRAS mutation incidence of gastric carcinomas

Year 2022, Volume: 12 Issue: 1, 1 - 5, 15.01.2022
https://doi.org/10.16899/jcm.979665

Abstract

Objectives: This study aims to determine the frequency of KRAS mutations in patients with gastric adenocarcinoma (GAC) in Hatay province, and to determine the relationship of this mutation with some pathological and clinical parameters and to guide the diagnosis and treatment planning of patients.
Methods: Formalin-fixed, paraffin-embedded, and histologically confirmed samples were used in the assessment of KRAS mutation. Sections were taken from the archive tissue samples of each case. Real-Time Polymerase Chain Reaction (RT-PCR) system was used to identify mutations of codons 12 and 13 (exon 2) of the RAS gene. Mutations of GLY12ALA (G12A), GLY12ASP (G12D), GLY12ARG (G12R), GLY12CYS (G12C), GLY12SER (G12S), GLY12VAL (G12V), GLY13ASP (G13D) were performed.
Results: The mutation rate of KRAS was 2% and only one substitution, G12D, was detected. In this case, the tumor was located in the small curvature. Since the number of cases with mutations was low, statistical comparison could not be made between KRAS mutation and clinicopathological factors. A significant difference was found between tumor differentiation and WHO-2010 typing and primary tumor stage.
Conclusions: We found the incidence of KRAS mutation to be 2%. We also estimate that the G12D mutation may be associated with GAC site and surgical margin. Although KRAS mutation in GAC alone is not a prognostic or predictive marker, subtype-specific analysis may provide data that may affect the diagnosis, management and treatment of the disease

Supporting Institution

BAP unit of Hatay Mustafa Kemal

Project Number

18.A.001.

References

  • 1. IARC-2019. International Agency for Research on Cancer. http://gco.iarc.fr/today/home. Date of access: September 13, 2019.
  • 2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-66.
  • 3. Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory. Eur. J Cancer 2015;51:1164-87.
  • 4. Ayatollahi H, Tavassoli A, Jafarian AH, Alavi A, Shakeri S, Shams SF, et al. KRAS codon 12 and 13 mutations in gastric cancer in the northeast Iran. Iran J Pathol 2018;13:167-72.
  • 5. Fu XH, Chen ZT, Wang WH, Fan XJ, Huang Y, Wu XB, et al. KRAS G12V mutation is an adverse prognostic factor of Chinese gastric cancer patients. J Cancer 2019;10:821-8.
  • 6. Qu JL, Qu XJ, Zhao MF, Teng YE, Zhang Y, Hou KZ, et al. Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis 2009;41:875-80.
  • 7. Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol 2003;56:1-9.
  • 8. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Canc 2007;7:295-308.
  • 9. Hewitt LC, Saito Y, Wang T, Matsuda Y, Oosting J, Silva ANS, et al. KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study. Gastric Cancer 2019;22:1193-203. 10. Kang JY, Park CK, Yeo CD, Lee HY, Rhee CK, Kim SJ, et al. Comparison of PNA clamping and direct sequencing for detecting KRAS mutations in matched tumour tissue, cell block, pleural effusion and serum from patients with malignant pleural effusion. Respirology 2015;20:138-46.
  • 11. Liu Z-M, Liu L-N, Li M, Zhang Q-P, Cheng S-H, Lu S. Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer. Oncology Reports 2009;22:515-20.
  • 12. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification ot Tumours of the Digestive System. (4th). IARC Press. (Lyon). 2010.
  • 13. Van Grieken NC, Aoyama T, Chambers PA, Bottomley D, Ward LC, Inam I, et al. KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study. Br J Cancer 2013;108:1495-501.
  • 14. TCGA. The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202-9.
  • 15. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, et al; Arbeitsgemeinschaft Internistische Onkologie and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14:490-9.
  • 16. Lu W, Wei H, Li M, Wang H, Liu L, Zhang Q, et al. Identification of KRAS and PIK3CA but not BRAF mutations in patients with gastric cancer. Mol Med Rep 2015;12:1219-24.
  • 17. Takahashi N, Yamada Y, Taniguchi H, Fukahori M, Sasaki Y, Shoji H, et al. Clinicopathological features and prognostic roles of KRAS, BRAF, PIK3CA and NRAS mutations in advanced gastric cancer. BMC Res Notes 2014;7:271.
  • 18. Polom K, Das K, Marrelli D, Roviello G, Pascale V, Voglino C, et al. KRAS Mutation in gastric cancer and prognostication associated with microsatellite instability status. Pathol Oncol Res 2019;25:333-40.
  • 19. Hewitt LC, Hutchins GG, Melotte V, Saito Y, Grabsch HI. KRAS, BRAF and gastric cancer. Transl Gastrointest Cancer 2015;4:429-47.
  • 20. Zhao W, Chan TL, Chu KM, Chan AS, Stratton MR, Yuen ST, et al. Mutations of BRAF and KRAS in gastric cancer and their association with microsatellite instability. Int J Cancer 2004;108:167-9.
  • 21. Kwon CH, Kim YK, Lee S, Kim A, Park HJ, Choi Y, et al. Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes. Histopathology 2018;72:556-68.
  • 22. Zhang J, Park D, Shin DM, Deng X. Targeting KRAS-mutant non-small cell lung cancer: challenges and opportunities. Acta Biochim Biophys Sin (Shanghai) 2016;48:11-6.
  • 23. Nodin B, Zendehrokh N, Sundstrom M, Jirstrom K. Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer. Diagn Pathol 2013;8:106.
  • 24. Lee KH, Lee JS, Suh C, Kim SW, Kim SB, Lee JH, et al. Clinicopathologic significance of the K-ras gene codon 12-point mutation in stomach cancer. an analysis of 140 cases. Cancer 1995;75:2794-801.

Mide Kanserlerinin Klinikopatolojik Özellikleri ve KRAS-mutasyon İnsidansı

Year 2022, Volume: 12 Issue: 1, 1 - 5, 15.01.2022
https://doi.org/10.16899/jcm.979665

Abstract

Amaç: Bu çalışmanın amacı, Hatay ilinde mide adenokarsinomlu (GAC) hastalarda KRAS mutasyonlarının sıklığını, bu mutasyonun bazı patolojik ve klinik parametrelerle ilişkisini belirlemek, hastaların tanı ve tedavi planlamasına rehberlik etmektir.

Gereç ve Yöntem: KRAS mutasyonunun değerlendirilmesinde formalinle fikse, parafine gömülmüş ve histolojik olarak tanıları doğrulanmış örnekler kullanıldı. Her vakanın arşiv doku örneklerinden kesitler alındı. RAS geninin 12 ve 13 kodonlarının (ekson 2) mutasyonlarını belirlemek için Gerçek Zamanlı Polimeraz Zincir Reaksiyonu (RT-PCR) sistemi kullanıldı. GLY12ALA (G12A), GLY12ASP (G12D), GLY12ARG (G12R), GLY12CYS (G12C), GLY12SER (G12S), GLY12VAL (G12V), GLY13ASP (G13D) mutasyonları çalışıldı.

Bulgular: KRAS mutasyon oranı %2 idi ve sadece G12D tespit edildi. Bu olguda, tümör küçük kurvatur yerleşimliydi. Mutasyonlu olgu sayısı az olduğundan KRAS mutasyonu ile klinikopatolojik faktörler arasında istatistiksel karşılaştırma yapılamadı. Tümör diferansiyasyonu ile WHO-2010 tiplemesi ve primer tümör evresi arasında anlamlı bir fark bulundu.

Sonuç: KRAS mutasyonu insidansını %2 olarak bulduk. GAC'deki KRAS mutasyonu tek başına prognostik veya prediktif bir belirteç olmasa da, alt tipe özgü analiz, hastalığın tanısını, yönetimini ve tedavisini etkileyebilecek veriler sağlayabilir.

Project Number

18.A.001.

References

  • 1. IARC-2019. International Agency for Research on Cancer. http://gco.iarc.fr/today/home. Date of access: September 13, 2019.
  • 2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-66.
  • 3. Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory. Eur. J Cancer 2015;51:1164-87.
  • 4. Ayatollahi H, Tavassoli A, Jafarian AH, Alavi A, Shakeri S, Shams SF, et al. KRAS codon 12 and 13 mutations in gastric cancer in the northeast Iran. Iran J Pathol 2018;13:167-72.
  • 5. Fu XH, Chen ZT, Wang WH, Fan XJ, Huang Y, Wu XB, et al. KRAS G12V mutation is an adverse prognostic factor of Chinese gastric cancer patients. J Cancer 2019;10:821-8.
  • 6. Qu JL, Qu XJ, Zhao MF, Teng YE, Zhang Y, Hou KZ, et al. Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis 2009;41:875-80.
  • 7. Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol 2003;56:1-9.
  • 8. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Canc 2007;7:295-308.
  • 9. Hewitt LC, Saito Y, Wang T, Matsuda Y, Oosting J, Silva ANS, et al. KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study. Gastric Cancer 2019;22:1193-203. 10. Kang JY, Park CK, Yeo CD, Lee HY, Rhee CK, Kim SJ, et al. Comparison of PNA clamping and direct sequencing for detecting KRAS mutations in matched tumour tissue, cell block, pleural effusion and serum from patients with malignant pleural effusion. Respirology 2015;20:138-46.
  • 11. Liu Z-M, Liu L-N, Li M, Zhang Q-P, Cheng S-H, Lu S. Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer. Oncology Reports 2009;22:515-20.
  • 12. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification ot Tumours of the Digestive System. (4th). IARC Press. (Lyon). 2010.
  • 13. Van Grieken NC, Aoyama T, Chambers PA, Bottomley D, Ward LC, Inam I, et al. KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study. Br J Cancer 2013;108:1495-501.
  • 14. TCGA. The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202-9.
  • 15. Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, et al; Arbeitsgemeinschaft Internistische Onkologie and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14:490-9.
  • 16. Lu W, Wei H, Li M, Wang H, Liu L, Zhang Q, et al. Identification of KRAS and PIK3CA but not BRAF mutations in patients with gastric cancer. Mol Med Rep 2015;12:1219-24.
  • 17. Takahashi N, Yamada Y, Taniguchi H, Fukahori M, Sasaki Y, Shoji H, et al. Clinicopathological features and prognostic roles of KRAS, BRAF, PIK3CA and NRAS mutations in advanced gastric cancer. BMC Res Notes 2014;7:271.
  • 18. Polom K, Das K, Marrelli D, Roviello G, Pascale V, Voglino C, et al. KRAS Mutation in gastric cancer and prognostication associated with microsatellite instability status. Pathol Oncol Res 2019;25:333-40.
  • 19. Hewitt LC, Hutchins GG, Melotte V, Saito Y, Grabsch HI. KRAS, BRAF and gastric cancer. Transl Gastrointest Cancer 2015;4:429-47.
  • 20. Zhao W, Chan TL, Chu KM, Chan AS, Stratton MR, Yuen ST, et al. Mutations of BRAF and KRAS in gastric cancer and their association with microsatellite instability. Int J Cancer 2004;108:167-9.
  • 21. Kwon CH, Kim YK, Lee S, Kim A, Park HJ, Choi Y, et al. Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes. Histopathology 2018;72:556-68.
  • 22. Zhang J, Park D, Shin DM, Deng X. Targeting KRAS-mutant non-small cell lung cancer: challenges and opportunities. Acta Biochim Biophys Sin (Shanghai) 2016;48:11-6.
  • 23. Nodin B, Zendehrokh N, Sundstrom M, Jirstrom K. Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer. Diagn Pathol 2013;8:106.
  • 24. Lee KH, Lee JS, Suh C, Kim SW, Kim SB, Lee JH, et al. Clinicopathologic significance of the K-ras gene codon 12-point mutation in stomach cancer. an analysis of 140 cases. Cancer 1995;75:2794-801.
There are 23 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Research
Authors

Didar Gürsoy 0000-0002-0674-7047

İlke Evrim Seçinti 0000-0002-8614-3971

Esin Doğan 0000-0003-3785-6032

Muhyittin Temiz 0000-0003-0780-5330

Project Number 18.A.001.
Publication Date January 15, 2022
Acceptance Date October 22, 2021
Published in Issue Year 2022 Volume: 12 Issue: 1

Cite

AMA Gürsoy D, Seçinti İE, Doğan E, Temiz M. Clinicopathologic features and KRAS mutation incidence of gastric carcinomas. J Contemp Med. January 2022;12(1):1-5. doi:10.16899/jcm.979665