Evaluation of Microsatellite Instability in  Colorectal Adenomas and Carcinomas by  Immunohistochemistry and a Comparison of  Histopathological Features

Rukiye Yılmaz; Recep Bedir; Remzi Adnan Akdoğan; Ahmet Pergel

doi:10.5152/EurJTher.2018.582

Authors

Rukiye Yılmaz Department of Pathology, Recep Tayyip Erdogan University, School of Medicine, Rize https://orcid.org/0000-0002-9389-9347
Recep Bedir Department of Pathology, Recep Tayyip Erdogan University, School of Medicine, Rize https://orcid.org/0000-0001-8247-3781
Remzi Adnan Akdoğan Department of Gastroenterology, Recep Tayyip Erdogan University, School of Medicine, Rize https://orcid.org/0000-0002-4151-3238
Ahmet Pergel Department of General Surgery, Recep Tayyip Erdogan University, School of Medicine, Rize https://orcid.org/0000-0002-0163-887X

DOI:

https://doi.org/10.5152/EurJTher.2018.582

Keywords:

Adenomatous polyps, colorectal carcinomas, immunohistochemistry, microsatellite instability

Abstract

Objective: Approximately 15% of sporadic colorectal carcinomas (CRCs) develop along the microsatellite instability (MSI) pathway. In this study, we compared the MLH1, MSH2, Ki-67, and p53 immunostaining properties with histopathological features of colorectal adenomas and CRCs.
Methods: A total of 102 cases were selected, including 50 adenomatous polyps, 25 adenocarcinomas, 10 adenocarcinomas with mucinous component, 14 mucinous adenocarcinomas, and three signet-ring cell carcinomas. The tissues were stained for MLH1, MSH2, p53, and Ki-67 primary antibodies.
Results: Negative staining was observed for MLH1 in 25% and MSH2 in 3.8% of all CRC cases. Compared with adenocarcinoma not otherwise specified (NOS), mucinous adenocarcinomas showed weaker staining for MLH1, which was statistically significant. There was also a statistically significant difference between adenocarcinoma NOS and signet-ring cell carcinomas in terms of negative staining for MLH1. A total of 69.2% of the MLH1-negative cases were high-grade. There was a statistically significant relationship between the histological grade and MLH1 negativity. A positive correlation was found between the grade of dysplasia and p53 staining intensity and Ki-67 proliferation index. No negative staining was observed for MLH1 and MSH2 in any of the adenomatous polyps.
Conclusion: For the histopathological examination of CRCs, in the presence of mucinous and poorly differentiated morphology, tumor-infiltrating lymphocytes and Crohn-like inflammatory response, immunohistochemical staining for MLH1, and MSH2 antibodies may be useful in the detection of tumors showing MSI.

Metrics

Metrics Loading ...

References

Fred T, Bosman FC, Ralph H, Hruban Neil D. Theise, ed. Tumours of the colon and rectum. 4 ed. WHO Clasification of Tumours of the Digestive System. 2010, International Agency for Research on Cancer: Lyon. 131-81.

Strum WB. Colorectal Adenomas. N Engl J Med 2016; 374: 1065-75.

Balbinotti RA1, Ribeiro U Jr, Sakai P, Safatle-Ribeiro AV, Balbinotti SS, Scapulatempo C, et al. hMLH1, hMSH2 and cyclooxygenase-2 (cox2) in sporadic colorectal polyps. Anticancer Res 2007; 27: 4465-71.

Hawkins NJ, Ward RL. Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst 2001; 93: 1307-13.

Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002; 20: 1043-8.

Overbeek LI, Ligtenberg MJ, Willems RW, Hermens RP, Blokx WA, Dubois SV, et al. Interpretation of immunohistochemistry for mismatch repair proteins is only reliable in a specialized setting. Am J Surg Pathol 2008; 32: 1246-51.

Jover R, Payá A, Alenda C, Poveda MJ, Peiró G, Aranda FI, et al., Defective mismatch-repair colorectal cancer: clinicopathologic characteristics and usefulness of immunohistochemical analysis for diagnosis. Am J Clin Pathol 2004; 12: 389-94.

Cawkwell L, Gray S, Murgatroyd H, Sutherland F, Haine L, Longfellow M, et al. Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair. Gut 1999; 45: 409-15.

Lieberman D, Moravec M, Holub J, Michaels L, Eisen G. Polyp size and advanced histology in patients undergoing colonoscopy screening: implications for CT colonography. Gastroenterology 2008; 135: 1100-5.

Basterra M, Gomez M, Mercado Mdel R, Irisarri R, Amorena E, Arrospide A, et al. Prevalence of altered mismatch repair protein nuclear expression detected by immunohistochemistry on adenomas with high-grade dysplasia and features associated with this risk in a population-based study. Gastroenterol Hepatol 2016; 39: 500-7.

Kang KJ, Min BH, Ryu K, Kim KM, Kim ER, Kim JY, et al., Clinical usefulness of microsatellite instability test in Korean young patients with high-risk features associated with adenoma. Clin Res Hepatol Gastroenterol 2012; 36: 378-83.

Lanza G, Gafà R, Santini A, Maestri I, Guerzoni L, Cavazzini L. Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol 2006; 24: 2359-67.

Erdamar S, Ucaryilmaz E, Demir G, Karahasanoglu T, Dogusoy G, Dirican A, et al. Importance of MutL homologue MLH1 and MutS homologue MSH2 expression in Turkish patients with sporadic colorectal cancer. World J Gastroenterol 2007; 13: 4437-44.

Kumarasinghe AP, de Boer B, Bateman AC, Kumarasinghe MP. DNA mismatch repair enzyme immunohistochemistry in colorectal cancer: a comparison of biopsy and resection material. Pathology 2010; 42: 414-20.

Kenney B, Deng Y, Mitchell K. Expression of p27, COX-2, MLH1, and MSH2 in young patients with colon carcinoma and correlation with morphologic findings. Hum Pathol 2013; 44: 591-7.

Andersen HS, Bertelsen CA, Henriksen R, Campos AH, Kristensen B, Ingeholm P, et al. The pathological phenotype of colon cancer with microsatellite instability. Dan Med J 2016; 63: pii: A5198.

Greenson JK, Bonner JD, Ben-Yzhak O. Phenotype of microsatellite unstable colorectal carcinomas: Well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability. Am J Surg Pathol 2003; 27: 563-70.

Compton CC. Colorectal carcinoma: diagnostic, prognostic, and molecular features. Mod Pathol 2003; 16: 376-88.

Alexander J, Watanabe T, Wu TT, Rashid A, Li S, Hamilton SR. Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 2001; 158: 527-35.

Graham DM, Appelman HD. Crohn’s-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Mod Pathol 1990; 3: 332-5.

Harrison JC, Dean PJ, el-Zeky F, Vander Zwaag R. From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 1994; 25: 498-505.