ORIGINAL ARTICLE
Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry
 
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Submission date: 2015-02-19
 
 
Final revision date: 2015-06-02
 
 
Acceptance date: 2015-07-02
 
 
Publication date: 2015-10-23
 
 
Pol J Pathol 2015;66(3):246-253
 
KEYWORDS
TOPICS
ABSTRACT
Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.
REFERENCES (44)
1.
Tárraga López PJ, Albero JS, Rodríguez-Montes JA. Primary and secondary prevention of colorectal cancer. Clin Med Insights Gastroenterol 2014; 7: 33-46.
 
2.
Jasperson KW, Tuohy TM, Neklason DW, et al. Hereditary and familial colon cancer. Gastroenterology 2010; 138: 2044-2058.
 
3.
Domingo E, Ramamoorthy R, Oukrif D, et al. Use of multivariate analysis to suggest a new molecular classification of colorectal cancer. J Pathol 2013; 229: 441-448.
 
4.
Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007; 50: 113-130.
 
5.
Gavin PG, Colangelo LH, Fumagalli D, et al. Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res 2012; 18: 6531-6541.
 
6.
Watanabe T, Wu TT, Catalano PJ, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 2001; 344: 1196-1206.
 
7.
Tejpar S, Bertagnolli M, Bosman F, et al. Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist 2010; 15: 390-404.
 
8.
Shia J, Tang LH, Vakiani E, et al. Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel. Am J Surg Pathol 2009; 33: 1639-1645.
 
9.
Hall G, Clarkson A, Shi A, et al. Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma. Pathology 2010; 42: 409-413.
 
10.
Hicks SC, Ward RL and Hawkins NJ. Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma. Pathology 2011; 43: 84-85; author reply 85-86.
 
11.
Saad RS, Ghorab Z, Khalifa MA, et al. CDX2 as a marker for intestinal differentiation: Its utility and limitations. World J Gastrointest Surg 2011; 3: 159-166.
 
12.
Beck F. The role of Cdx genes in the mammalian gut. Gut 2004; 53: 1394-1396.
 
13.
Kaimaktchiev V, Terracciano L, Tornillo L, et al. The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas. Mod Pathol 2004; 17: 1392-1399.
 
14.
Palmer DG, Paraskeva C, Williams AC. Modulation of p53 expression in cultured colonic adenoma cell lines by the naturally occurring lumenal factors butyrate and deoxycholate. Int J Cancer 1997; 73: 702-706.
 
15.
Popat S, Chen Z, Zhao D, et al. A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. Ann Oncol 2006; 17: 1810-1817.
 
16.
Einspahr JG, Martinez ME, Jiang R, et al. Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics. Cancer Epidemiol Biomarkers Prev 2006; 15: 1443-1450.
 
17.
Tsanou E, Peschos D, Batistatou A, et al. The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Res 2008; 28: 3815-3826.
 
18.
Elzagheid A, Kuopio T, Ilmen M, et al. Prognostication of invasive ductal breast cancer by quantification of E-cadherin immunostaining: the methodology and clinical relevance. Histopathology 2002; 41: 127-133.
 
19.
Lugli A, Tzankov A, Zlobec I, et al. Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status. Mod Pathol 2008; 21: 1403-1412.
 
20.
Moskaluk CA, Zhang H, Powell SM, et al. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol 2003; 16: 913-919.
 
21.
Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 2003; 27: 303-310.
 
22.
Bakaris S, Cetinkaya A, Ezberci F, et al. Expression of homeodomain protein CDX2 in colorectal adenoma and adenocarcinoma. Histol Histopathol 2008; 23: 1043-1047.
 
23.
Hinoi T, Tani M, Lucas PC, et al. Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol 2001; 159: 2239-2248.
 
24.
Choi BJ, Kim CJ, Cho YG, et al. Altered expression of CDX2 in colorectal cancers. APMIS 2006; 114: 50-54.
 
25.
Baba Y, Nosho K, Shima K, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res 2009; 15: 4665-4673.
 
26.
Rosty C, Williamson EJ, Clendenning M, et al. Should the grading of colorectal adenocarcinoma include microsatellite instability status? Hum Pathol 2014; 45: 2077-2084.
 
27.
Mogoanta SS, Vasile I, Totolici B, et al. Colorectal cancer – clinical and morphological aspects. Rom J Morphol Embryol 2014; 55: 103-110.
 
28.
Elzagheid A, Algars A, Bendardaf R, et al. E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. World J Gastroenterol 2006; 12: 4304-4309.
 
29.
He X, Chen Z, Jia M, et al. Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis. PLoS One 2013; 8: e70858.
 
30.
Jass JR. HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam Cancer 2004; 3: 93-100.
 
31.
Kaur G, Masoud A, Raihan N, et al. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma. Indian J Med Res 2011; 134: 186-192.
 
32.
Kim JH, Rhee YY, Bae JM, et al. Loss of CDX2/CK20 expression is associated with poorly differentiated carcinoma, the CpG island methylator phenotype, and adverse prognosis in microsatellite-unstable colorectal cancer. Am J Surg Pathol 2013; 37: 1532-1541.
 
33.
Minoo P, Zlobec I, Peterson M, et al. Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles. Int J Oncol 2010; 37: 707-718.
 
34.
Okon K, Zazula M, Rudzki Z, et al. CDX-2 expression is reduced in colorectal carcinomas with solid growth pattern and proximal location, but is largely independent of MSI status. Pol J Pathol 2004; 55: 9-14.
 
35.
Zlobec I, Bihl M, Foerster A, et al. Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features. J Pathol 2011; 225: 336-343.
 
36.
Funakoshi S, Kong J, Crissey MA, et al. Intestine-specific transcription factor Cdx2 induces E-cadherin function by enhancing the trafficking of E-cadherin to the cell membrane. Am.
 
37.
J Physiol Gastrointest Liver Physiol 2010; 299: G1054-1067.
 
38.
Lugli A, Zlobec I, Minoo P, et al. Prognostic significance of the wnt signalling pathway molecules APC, beta-catenin and E-cadherin in colorectal cancer: a tissue microarray-based analysis. Histopathology 2007; 50: 453-464.
 
39.
Yalcinkaya U, Ozturk E, Ozgur T, et al. P53 expression in synchronous colorectal cancer. Saudi Med J 2008; 29: 826-831.
 
40.
Demirbas S, Sucullu I, Yildirim S, et al. Influence of the c-erb B-2, nm23, bcl-2 and p53 protein markers on colorectal cancer. Turk J Gastroenterol 2006; 17: 13-19.
 
41.
Carneiro FP, Ramalho LN, Britto-Garcia S, et al. Immunohistochemical expression of p16, p53, and p63 in colorectal adenomas and adenocarcinomas. Dis Colon Rectum 2006; 49: 588-594.
 
42.
Zhao DP, Ding XW, Peng JP, et al. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma. J Zhejiang Univ Sci B 2005; 6: 1163-1169.
 
43.
Olsen J, Espersen ML, Jess P, et al. The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. Surg Oncol 2014; 23: 167-176.
 
44.
Valentini AM, Renna L, Armentano R, et al. Mismatch repair, p53 and beta-catenin proteins in colorectal cancer. Anticancer Res 2002; 22: 2083-2088.
 
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