Abstract
CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2–40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2–40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2–40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2–40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2–40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2–40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.
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Ferlay J, Soerjomataram I, Ervik M, et al.: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer 2013. http://globocan.iarc.fr. Accessed on 23 May 2015.
Foda AA, El-Hawary AK, Abdel-Aziz A (2013) Differential expression of matrix metalloproteinase- 13 in mucinous and nonmucinous colorectal carcinomas. Ann Diagn Pathol 17:347–353
Hamilton SR, Bosman FT, Boffetta P, et al. (2010) Tumors of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, et al. (eds) WHO Classification of tumors of the digestive system. IARCPress, Lyon, pp. 132–182
Mekenkamp JM, Heesterbeek KJ, Koopman M, et (2012) Mucinous adenocarcinomas: Poor prognosis in metastatic colorectal cancer. Eur J Cancer, 48: 501–509.
Ordonez NG (2005) D2–40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol 205:372–380
Ordonez NG (2006) Value of immunohistochemistry in distinguishing peritoneal mesothelioma from serous carcinoma of the ovary and peritoneum: a review and update. Adv Anat Pathol 13:16–25
Rogers JH (1987) Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons. J Cell Biol 105:1343–1353
Gander JC, Gotzos V, Fellay B, et al. (1996) Inhibition of the proliferative cycle and apoptotic events in WiDr cells after down-regulation of the calcium-binding protein calretinin using antisense oligodeoxynucleotides. Exp Cell Res 225:399–410
Miettinen M, Limon J, Niezabitowski A, et al. (2001) Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma. Am J Surg Pathol 25:610–617
Lugli A, Forster Y, Haas P, et al. (2003) Calretinin expression in human normal and neoplastic tissues: a tissue microarray analysis on 5233 tissue samples. Hum Pathol. 34:994–1000
Dent R, Hanna WM, Trudeau M, et al. (2009) Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat 115:423–428
Winn B, Tavares R, Fanion J, et al. (2009) Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Hum Pathol 40:398–404
Chu AU, Litzky LA, Pasha TL, et al. (2005) Utility of D2–40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Mod Pathol 18:105–110
Chang K, Pastan I (1994) Molecular cloning and expression of a cDNA encoding a protein detected by the K1 antibody from an ovarian carcinoma (OVCAR-3) cell line. Int J Cancer 57:90–97
Ordonez NG (2003) Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol 27:1418–1428
Cheng YW, Idrees K, Shattock R, et al. (2010) Loss of imprinting and marked gene elevation are 2 forms of aberrant IGF2 expression in colorectal cancer. Int J Cancer 127:568–577
Li H, Zhao P, Lu Y (2012) Correlation of aberrant expression of CD133 with FHIT and malignant phenotype of colorectal adenocarcinoma. Int J Colorectal Dis 27:1015–1020
Lee SJ, Choi SY, Kim WJ, et al. (2013) Combined aberrant expression of E-cadherin and S100 A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients. Diagn Pathol 19(8):99
Foda AA (2013) No-cost manual method for preparation of tissue microarrays having high quality comparable to semiautomated methods. Appl Immunohistochem Mol Morphol 21:271–274
Takeshima Y, Amatya VJ, Kushitani K, et al. (2008) A Useful antibody panel for differential diagnosis between peritoneal mesothelioma and ovarian serous carcinoma in japanese cases. Am J Clin Pathol 130:771–779
Ordóñez NG (2003) Value of mesothelin immunostaining in the diagnosis of mesothelioma. Mod Pathol 16(3):192–197
Hanna A, Pang Y, Bedrossian CW, et al. (2010) Podoplanin is a useful marker for identifying mesothelioma in malignant effusions. Diagn Cytopathol 38(4):264–269
Cargnello R, Celio MR, Schwaller B, et al. (1996) Change of calretinin expression in the human colon adenocarcinoma cell line HT29 after differentaition. Biochim Biophys Acta 1313:201–208
Taliano RJ, Lu S, Singh K, et al. (2013) Calretinin expression in high-grade invasive ductal carcinoma of the breast is associated with basal-like subtype and unfavorable prognosis. Hum Pathol 44(12):2743–2750
Gotzos V, Wintergerst ES, Musy JP, et al. (1999) Selective distribution of calretinin in adenocarcinomas of the human colon and adjacent tissues. Am J Surg Pathol 23:701–711
Purdie CA, Piris J (2000) Histopathological grade, mucinous differentiation and DNA ploidy in relation to prognosis in colorectal carcinoma. Histopathol 36:121–126
Niv Y (2000) Mucin and colorectal cancer. IMAJ 2:775–777
Kahn HJ, Marks A (2002) A new monoclonal antibody, D2–40, for detection of lymphatic invasion in primary tumors. Lab Invest 82:1255–1257
Raica M, Cimpean AM, Ribatti D (2008) The Role of podoplanin in tumor progression and metastasis. Anticancer Res 28:2997–3006
Kawamata F, Homma S, Kamachi H, et al. (2014) C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma. J Gastroenterol 49:81–92
Liebig B, Brabletz T, Staege MS, et al. (2005) Forced expression of deltaN-TCF-1B in colon cancer derived cell lines is accompanied by the induction of CEACAM5/6 and mesothelin. Cancer Lett 223:159–167
Foda AA, El-Hawary AK, Aziz AA (2015) Colorectal adenocarcinoma with mucinous component: relation of MMP-13, EGFR, and E-cadherin expressions to clinicopathological features and prognosis. APMIS. doi:10.1111/apm.12379
Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, et al. (2009) Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 69:4116–4124
Zhu QC, Gao RY, Wu W, et al. (2013) Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer. Asian Pacific J Cancer Prev 14(5):2689–2698
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Foda, A.A.M., El-Hawary, A.K. & Hamed, H. Aberrant Expression of Calretinin, D2–40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis. Pathol. Oncol. Res. 22, 725–732 (2016). https://doi.org/10.1007/s12253-016-0060-y
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DOI: https://doi.org/10.1007/s12253-016-0060-y