ORIGINAL ARTICLE
Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma
1
Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland
2
Department of Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
3
Department of Oncological Surgery, Medical University of Gdańsk, Gdańsk, Poland
4
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
5
Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
6
Chair of Oncological Surgery, Collegium Medicum, Nicolaus Copernicus University; Oncology Centre, Bydgoszcz, Poland
7
Department of Clinical Oncology, Centre of Oncology, Bydgoszcz, Poland
8
Department of Clinical Oncology of the University Clinical Centre, Silesian Medical University, Katowice, Poland
9
Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria
10
Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical
University of Gdańsk, Gdańsk, Poland
Submission date: 2016-04-22
Final revision date: 2016-10-09
Acceptance date: 2016-11-06
Publication date: 2016-11-25
Corresponding author
Piotr Czapiewski
Department of Pathomorphology Medical University of Gdańsk Debinki 7 80-952 Gdańsk, Poland
Department of Pathomorphology Medical University of Gdańsk Debinki 7 80-952 Gdańsk, Poland
Pol J Pathol 2016;67(3):228-234
KEYWORDS
TOPICS
ABSTRACT
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN–, 85 cases).
Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN– group.
K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival.
We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.
Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN– group.
K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival.
We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.
REFERENCES (26)
1.
Fitzmaurice C, Dicker D, Pain A, et al. The Global Burden of Cancer 2013; JAMA Oncol 2015; 1: 505-527.
2.
Lin HH, Yang HL, Lin JK, et al. The Number of risk factors determines the outcome of stage II colorectal cancer patients. Hepatogastroenterology 2014; 61: 1024-1027.
3.
Parnaby CN, Scott NW, Ramsay G, et al. Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection. Br J Cancer 2015; 113: 212-219.
4.
Resch A, Harbaum L, Pollheimer MJ, et al. Grading lymph node metastasis: a feasible approach for prognostication of patients with stage III colorectal cancer. J Clin Pathol 2015; 68: 742-745.
5.
Resch A, Langner C. Lymph node staging in colorectal cancer: old controversies and recent advances. World J Gastroenterol 2013; 19: 8515-8526.
6.
Benson AB, Bekaii-Saab T, Chan E, et al. Metastatic colon cancer, version 3.2013: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 2013; 11: 141-152.
7.
Markiewicz A, Ksiazkiewicz M, Seroczynska B, et al. Heterogeneity of mesenchymal markers expression-molecular profiles of cancer cells disseminated by lymphatic and hematogenous routes in breast cancer. Cancers (Basel) 2013; 5: 1485-1503.
8.
Markiewicz A, Ahrends T, Welnicka-Jaskiewicz M, et al. Expression of epithelial to mesenchymal transition-related markers in lymph node metastases as a surrogate for primary tumor metastatic potential in breast cancer. J Transl Med 2012; 10: 226.
9.
Karantza V. Keratins in health and cancer: more than mere epithelial cell markers. Oncogene 2011; 30: 127-138.
10.
Fillies T, Werkmeister R, Packeisen J, et al. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity. BMC Cancer 2006; 6: 10.
11.
Makino T, Yamasaki M, Takeno A, et al. Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer 2009; 101: 1298-1306.
12.
Oue N, Noguchi T, Anami K, et al. Cytokeratin 7 is a predictive marker for survival in patients with esophageal squamous cell carcinoma. Ann Surg Oncol 2012; 19: 1902-1910.
13.
Govaere O, Komuta M, Berkers J, et al. Keratin 19: a key role player in the invasion of human hepatocellular carcinomas. Gut 2014; 63: 674-685.
14.
Landau MS, Kuan SF, Chiosea S, Pai RK. BRAF-mutated microsatellite stable colorectal carcinoma: an aggressive adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical expression. Hum Pathol 2014; 45: 1704-1712.
15.
Tatsumi N, Kushima R, Vieth M, et al. Cytokeratin 7/20 and mucin core protein expression in ulcerative colitis-associated colorectal neoplasms. Virchows Arch 2006; 448: 756-762.
16.
Bayrak R, Yenidunya S, Haltas H. Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract 2011; 207: 156-160.
17.
Harbaum L, Pollheimer MJ, Kornprat P, et al. Keratin 7 expression in colorectal cancer – freak of nature or significant finding? Histopathology 2011; 59: 225-234.
18.
Zalata KR, Elshal MF, Foda AA, Shoma A. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression – a pilot study. Tumour Biol 2015; 36: 6579-6584.
19.
Messick CA, Church JM, Liu X, et al. Stage III colorectal cancer: molecular disparity between primary cancers and lymph node metastases. Ann Surg Oncol 2010; 17: 425-431.
20.
McKay JA, Douglas JJ, Ross VG, et al. Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Aberdeen Colorectal Initiative. Int J Cancer 2000; 88: 77-81.
21.
Marsh S, McKay JA, Curran S, et al. Primary colorectal tumour is not an accurate predictor of thymidylate synthase in lymph node metastasis. Oncol Rep 2002; 9: 231-234.
22.
Zhang JS, Caplin S, Bosman FT, Benhattar J. Genetic diversity at the p53 locus between primary human colorectal adenocarcinomas and their lymph-node metastases. Int J Cancer 1997; 70: 674-678.
23.
Meteoglu I, Erdogdu IH, Tuncyurek P, et al. Nuclear factor kappa B, matrix metalloproteinase-1, p53, and Ki-67 expressions in the primary tumors and the lymph node metastases of colorectal cancer cases. Gastroenterol Res Pract 2015; 2015: 945392.
24.
Ohrling K, Edler D, Hallstrom M, et al. Detection of thymidylate synthase expression in lymph node metastases of colorectal cancer can improve the prognostic information. J Clin Oncol 2005; 23: 5628-5634.
25.
Deng Y, Kurland BF, Wang J, et al. High epidermal growth factor receptor expression in metastatic colorectal cancer lymph nodes may be more prognostic of poor survival than in primary tumor. Am J Clin Oncol 2009; 32: 245-252.
26.
Karamitopoulou E, Zlobec I, Koumarianou A, et al. Expression of p16 in lymph node metastases of adjuvantly treated stage III colorectal cancer patients identifies poor prognostic subgroups: a retrospective analysis of biomarkers in matched primary tumor and lymph node metastases. Cancer 2010; 116: 4474-4486.
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
