Research Article
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Year 2024, Volume: 14 Issue: 2, 131 - 137, 29.08.2024

Abstract

References

  • 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.
  • 2. Burgart LJ, Chopp WV, Jain D, with guidance from CAP Cancer and CAP Pathology Electronic Reporting Committees. Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. Version:4.2.0.2. Protocol posting date: June 2022.
  • 3. American society of clinical oncology. Colorectal cancer: Types of treatment. https://www.cancer. net/cancer-types/colorectalcancer/types-treatment;05/2022 [accessed 01.07.2023].
  • 4. Losso GM, Moraes RS, Gentili AC, Messias-Reason IT. Microsatellite instability-MSI markers (BAT26, BAT25, D2S123, D5S346, D17S250) in rectal cancer. Arq Bras Cir Dig. 2012;25:240–4.
  • 5. Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, et al. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 2006;8:305–11.
  • 6. Nguyen HT, Duong H-Q. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy. Oncol Lett. 2018;16:9–18.
  • 7. Keskin SE, Güzdolu E, Sertdemir N, Demir G, Sünnetçi D, Çabuk D, et al. The mutation profiles of K-RAS/N-RAS genes in metastatic colorectal cancer patients. KOU Sag Bil Derg. 2022;8(3):172–8.
  • 8. Çokmert S, Altun Z, Öztop I, Aktaş S, Olgun N. Kolorektal Kanser ve İmmünoterapi. DEÜ Tıp Fak Derg. 2016;30(3):131–7.
  • 9. Bartlett JMS, Shaaban A, Schmitt F. Molecular pathology: A practical guide for surgical pathologist and cytopathologist. United Kingdom: Cambridge University Press, 2015:200–21.
  • 10. Tariq K, Ghias K. Colorectal cancer carcinogenesis: A review of mechanisms. Cancer Biol Med. 2016;13:120–35.
  • 11. Kim JH, Kim KJ, Bae JM, Rhee YE, Cho NY, Lee HS, et al. Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma. J Clin Pathol. 2015;68:22–8.
  • 12. Ueno H, Hashiguchi Y, Shimazaki H, Shinto E, Kajiwara Y, Nakanishi K, et al. Objective criteria for Crohn-like lymphoid reaction in colorectal cancer. Am J Clin Pathol. 2013;139:434–41.
  • 13. Vayrynen JP, Sajanti SA, Klintrup K, Makela J, Herzig KH, Karttunen TJ, et al. Characteristics and significance of colorectal cancer associated lymphoid reaction. Int J Cancer. 2014;134:2126–35.
  • 14. Klintrup K, Makinen JM, Kauppila S, Vare PO, Melkko J, Touminen H, et al. Inflammation and prognosis in colorectal cancer. Eur J Cancer. 2005;41:2645–54.
  • 15. Jakubowska K, Kisielewski W, Kanczuga-Koda L, Koda M, Famulski W. Stromal and intraepithelial tumorinfiltrating lymphocytes in colorectal carcinoma. Oncol Lett. 2017;14:6421–32.
  • 16. Caporale A, Vestri AR, Benvenuto E, Giluliani A, Mingazzini P, Angelico F. Is desmoplasia a protective factor for survival in patients with colorectal carcinoma? Clin Gastroenterol Hepatol. 2005;3:370–5.
  • 17. Ueno H, Jones AM, Wilkinson KH, Jass JR, Talbot IC. Histological categorization of fibrotic cancer stroma in advanced rectal cancer. Gut. 2004;53:581–6.
  • 18. Conti J, Thomas G. The role of tumor stroma in colorectal cancer invasion and metastasis. Cancers (Basel) . 2011;3:2160–8.
  • 19. Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, et al. Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res. 2007;13:2082–90.
  • 20. Shin N, Son GM, Shin DH, Kwon MS, Park BS, Kim HS, et al. Cancer-associated fibroblasts and desmoplastic reactions related to cancer invasiveness in patients with colorectal cancer. Ann Coloproctol. 2019;35:36–46.
  • 21. Rozek LS, Schmit SL, Greenson JK, Tomsho LP, Rennert HS, Rennert G, et al. Tumor-infiltrating lymphocytes, Crohn’s-like lymphoid reaction, and survival from colorectal cancer. J Natl Cancer Inst. 2016;108: djw027.
  • 22. Hu X, Li YQ, Li QG, Ma YL, Peng JJ, Cai SJ. ITGAE defines CD8+ tumor-infiltrating lymphocytes predicting a better prognostic survival in colorectal cancer. Ebiomedicine. 2018;35:178–88.
  • 23. Fujiyoshi K, Vayrnen JP, Borowsky J, Papke DJ, Arima K, Haruki K, et al. Tumor budding, poorly differentiated clusters, and T-cell response in colorectal cancer. Ebiomedicine. 2020;57:102860.
  • 24. Graham RP, Viekart RA, Tillmans LS, Wang AH, Laird PW, Weisenberg DJ, et al. Tumor budding in colorectal carcinoma: Confirmation of prognostic significance and histologic cut off in a population-based cohort. Am J Surg Pathol. 2015;39:1340–6.
  • 25. Lee HS, Hwang DY, Han HS. Histology and its prognostic effect on KRAS-mutated colorectal carcinomas in Korea. Oncol Lett. 2020;20:655–66.
  • 26. Akimoto N, Vayrynen JP, Zhao M, Ugari T, Fujiyoshi K, Borowsky J, et al. Desmoplastic reaction, immune cell response, and prognosis in colorectal cancer. Front Immunol. 2022;13:840198.
  • 27. Bonetti LR, Baressi V, Maiorana A, Manfredini S, Caprera C, Bettelli S. Clinical impact and prognostic role of KRAS/ BRAF/PIK3CA mutations in stage I colorectal cancer. Dis Markers. 2018;2018:2959801.
  • 28. Niu W, Wang G, Feng J, Li Z, Li C, Shan B. Correlation between microsatellite instability and RAS gene mutation and stage III colorectal cancer. Oncol Lett. 2018;17:332–8.
  • 29. Huang CJ, Huang SH, Chien CC, Lee HHC, Yang SH, Chang CC, et al. Impact of microsatellite status on chemotherapy for colorectal cancer patients with KRAS or BRAF mutation. Oncol Lett. 2016;12:4427–34.
  • 30. Taieb J, Malicot K Le, Shi Q, Penault-Llorca F, Bouche O, Tabernero J, et al. Prognostic value of BRAF and KRAS Mutations in MSI and MSS stage III colon cancer. Natl Cancer Inst. 2017;109: djw272

Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience

Year 2024, Volume: 14 Issue: 2, 131 - 137, 29.08.2024

Abstract

Aim: Microsatellite instability (MSI) and KRAS mutations change colorectal carcinoma (CRC) treatment protocols. Advanced examinations such as immunohistochemistry and polymerase chain reaction (PCR) are required to determine MSI and KRAS mutations. On the other hand, Crohn-like lymphoid reaction (CLR), tumor-infiltrating lymphocytes (TIL), tumor budding (TB), and desmoplastic response (DR) are histomorphologic features that can be determined only with routine hematoxylin-eosin (H&E) sections. Our study aimed to evaluate relationships between MSI, KRAS mutations, and histomorphologic features. It was thought that the relationships to be determined may be useful in predicting KRAS mutations and MSI by evaluating only H&E sections.
Material and Method: One hundred nine metastatic CRC cases were reviewed retrospectively. Polymerase chain reaction results were obtained from the molecular pathology report archive and performed on all cases for KRAS mutation detection upon clinical request during routine pathologic examinations. MLH1, MSH2, MSH6, and PMS2 immunohistochemistry, performed on 70 cases for MSI interpretation upon clinical request during routine pathological examinations, was re-evaluated for standardization. Routine H&E sections with tumors were examined for CLR, TIL, TB, and DR according to study-specific criteria.
Results: KRAS mutations were found in 35.77% (39/109), MSI in 24.28% (17/70), CLR in 32.11% (35/109), TIL in 44.95% (49/109), TB in 73.39% (80/109), DR in 84.40% (92/109) of the cases. CLR, TIL, DR, and KRAS mutations were higher in microsatellite stable (MSS) cases, and TB was higher in MSI cases. Crohn-like lymphoid reaction, TIL, DR, and MSI were higher in KRAS wild cases, and TB in KRAS mutant cases. Only the MSS-DR correlation was statistically significant.
Conclusion: The MSS-DR correlation was statistically significant in our study. However, desmoplasia was determined in 92.45% of MSS cases, and was also determined in 58.82% of MSI cases. Because DR is an expected feature in tumor stroma, its guidance in terms of MSI was limited. Also, no significant relationship was found between MSI and DR in Turkish or English literature. In our study, histomorphologic features were insufficient to predict MSI and KRAS mutations. It is vital to immediately refer patients with metastases evaluated in centers without immunohistochemistry and PCR facilities to an advanced center for MSI and KRAS mutation determination diagnosing CRC, especially for treatment selection.

References

  • 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.
  • 2. Burgart LJ, Chopp WV, Jain D, with guidance from CAP Cancer and CAP Pathology Electronic Reporting Committees. Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. Version:4.2.0.2. Protocol posting date: June 2022.
  • 3. American society of clinical oncology. Colorectal cancer: Types of treatment. https://www.cancer. net/cancer-types/colorectalcancer/types-treatment;05/2022 [accessed 01.07.2023].
  • 4. Losso GM, Moraes RS, Gentili AC, Messias-Reason IT. Microsatellite instability-MSI markers (BAT26, BAT25, D2S123, D5S346, D17S250) in rectal cancer. Arq Bras Cir Dig. 2012;25:240–4.
  • 5. Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, et al. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 2006;8:305–11.
  • 6. Nguyen HT, Duong H-Q. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy. Oncol Lett. 2018;16:9–18.
  • 7. Keskin SE, Güzdolu E, Sertdemir N, Demir G, Sünnetçi D, Çabuk D, et al. The mutation profiles of K-RAS/N-RAS genes in metastatic colorectal cancer patients. KOU Sag Bil Derg. 2022;8(3):172–8.
  • 8. Çokmert S, Altun Z, Öztop I, Aktaş S, Olgun N. Kolorektal Kanser ve İmmünoterapi. DEÜ Tıp Fak Derg. 2016;30(3):131–7.
  • 9. Bartlett JMS, Shaaban A, Schmitt F. Molecular pathology: A practical guide for surgical pathologist and cytopathologist. United Kingdom: Cambridge University Press, 2015:200–21.
  • 10. Tariq K, Ghias K. Colorectal cancer carcinogenesis: A review of mechanisms. Cancer Biol Med. 2016;13:120–35.
  • 11. Kim JH, Kim KJ, Bae JM, Rhee YE, Cho NY, Lee HS, et al. Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma. J Clin Pathol. 2015;68:22–8.
  • 12. Ueno H, Hashiguchi Y, Shimazaki H, Shinto E, Kajiwara Y, Nakanishi K, et al. Objective criteria for Crohn-like lymphoid reaction in colorectal cancer. Am J Clin Pathol. 2013;139:434–41.
  • 13. Vayrynen JP, Sajanti SA, Klintrup K, Makela J, Herzig KH, Karttunen TJ, et al. Characteristics and significance of colorectal cancer associated lymphoid reaction. Int J Cancer. 2014;134:2126–35.
  • 14. Klintrup K, Makinen JM, Kauppila S, Vare PO, Melkko J, Touminen H, et al. Inflammation and prognosis in colorectal cancer. Eur J Cancer. 2005;41:2645–54.
  • 15. Jakubowska K, Kisielewski W, Kanczuga-Koda L, Koda M, Famulski W. Stromal and intraepithelial tumorinfiltrating lymphocytes in colorectal carcinoma. Oncol Lett. 2017;14:6421–32.
  • 16. Caporale A, Vestri AR, Benvenuto E, Giluliani A, Mingazzini P, Angelico F. Is desmoplasia a protective factor for survival in patients with colorectal carcinoma? Clin Gastroenterol Hepatol. 2005;3:370–5.
  • 17. Ueno H, Jones AM, Wilkinson KH, Jass JR, Talbot IC. Histological categorization of fibrotic cancer stroma in advanced rectal cancer. Gut. 2004;53:581–6.
  • 18. Conti J, Thomas G. The role of tumor stroma in colorectal cancer invasion and metastasis. Cancers (Basel) . 2011;3:2160–8.
  • 19. Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, et al. Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res. 2007;13:2082–90.
  • 20. Shin N, Son GM, Shin DH, Kwon MS, Park BS, Kim HS, et al. Cancer-associated fibroblasts and desmoplastic reactions related to cancer invasiveness in patients with colorectal cancer. Ann Coloproctol. 2019;35:36–46.
  • 21. Rozek LS, Schmit SL, Greenson JK, Tomsho LP, Rennert HS, Rennert G, et al. Tumor-infiltrating lymphocytes, Crohn’s-like lymphoid reaction, and survival from colorectal cancer. J Natl Cancer Inst. 2016;108: djw027.
  • 22. Hu X, Li YQ, Li QG, Ma YL, Peng JJ, Cai SJ. ITGAE defines CD8+ tumor-infiltrating lymphocytes predicting a better prognostic survival in colorectal cancer. Ebiomedicine. 2018;35:178–88.
  • 23. Fujiyoshi K, Vayrnen JP, Borowsky J, Papke DJ, Arima K, Haruki K, et al. Tumor budding, poorly differentiated clusters, and T-cell response in colorectal cancer. Ebiomedicine. 2020;57:102860.
  • 24. Graham RP, Viekart RA, Tillmans LS, Wang AH, Laird PW, Weisenberg DJ, et al. Tumor budding in colorectal carcinoma: Confirmation of prognostic significance and histologic cut off in a population-based cohort. Am J Surg Pathol. 2015;39:1340–6.
  • 25. Lee HS, Hwang DY, Han HS. Histology and its prognostic effect on KRAS-mutated colorectal carcinomas in Korea. Oncol Lett. 2020;20:655–66.
  • 26. Akimoto N, Vayrynen JP, Zhao M, Ugari T, Fujiyoshi K, Borowsky J, et al. Desmoplastic reaction, immune cell response, and prognosis in colorectal cancer. Front Immunol. 2022;13:840198.
  • 27. Bonetti LR, Baressi V, Maiorana A, Manfredini S, Caprera C, Bettelli S. Clinical impact and prognostic role of KRAS/ BRAF/PIK3CA mutations in stage I colorectal cancer. Dis Markers. 2018;2018:2959801.
  • 28. Niu W, Wang G, Feng J, Li Z, Li C, Shan B. Correlation between microsatellite instability and RAS gene mutation and stage III colorectal cancer. Oncol Lett. 2018;17:332–8.
  • 29. Huang CJ, Huang SH, Chien CC, Lee HHC, Yang SH, Chang CC, et al. Impact of microsatellite status on chemotherapy for colorectal cancer patients with KRAS or BRAF mutation. Oncol Lett. 2016;12:4427–34.
  • 30. Taieb J, Malicot K Le, Shi Q, Penault-Llorca F, Bouche O, Tabernero J, et al. Prognostic value of BRAF and KRAS Mutations in MSI and MSS stage III colon cancer. Natl Cancer Inst. 2017;109: djw272
There are 30 citations in total.

Details

Primary Language English
Subjects Pathology
Journal Section Research Article
Authors

Gizem Ay Haldız

Ümit Çobanoğlu

Publication Date August 29, 2024
Submission Date December 4, 2023
Acceptance Date March 14, 2024
Published in Issue Year 2024 Volume: 14 Issue: 2

Cite

APA Ay Haldız, G., & Çobanoğlu, Ü. (2024). Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience. Kafkas Journal of Medical Sciences, 14(2), 131-137.
AMA Ay Haldız G, Çobanoğlu Ü. Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience. KAFKAS TIP BİL DERG. August 2024;14(2):131-137.
Chicago Ay Haldız, Gizem, and Ümit Çobanoğlu. “Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience”. Kafkas Journal of Medical Sciences 14, no. 2 (August 2024): 131-37.
EndNote Ay Haldız G, Çobanoğlu Ü (August 1, 2024) Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience. Kafkas Journal of Medical Sciences 14 2 131–137.
IEEE G. Ay Haldız and Ü. Çobanoğlu, “Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience”, KAFKAS TIP BİL DERG, vol. 14, no. 2, pp. 131–137, 2024.
ISNAD Ay Haldız, Gizem - Çobanoğlu, Ümit. “Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience”. Kafkas Journal of Medical Sciences 14/2 (August 2024), 131-137.
JAMA Ay Haldız G, Çobanoğlu Ü. Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience. KAFKAS TIP BİL DERG. 2024;14:131–137.
MLA Ay Haldız, Gizem and Ümit Çobanoğlu. “Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience”. Kafkas Journal of Medical Sciences, vol. 14, no. 2, 2024, pp. 131-7.
Vancouver Ay Haldız G, Çobanoğlu Ü. Comparison of KRAS Mutation, Microsatellite Instability and Histomorphologic Features in Metastatic Colorectal Carcinomas: Single Centre Experience. KAFKAS TIP BİL DERG. 2024;14(2):131-7.