The Importance of Expression of Keratin 17 (KRT17) and SPINK1 in Neoplastic (Invasive and Noninvasive) Lesions of the Bladder

Amaç: Mesane kanserlerinin tanı ve derecelendirilmesi tedavi ve prognoz üzerinde önemli bir etkiye sahiptir. Ancak günümüzde mesanenin neoplastik lezyonlarının ayırıcı tanısında kullanılabilecek çok hassas ve spesifik immünohistokimyasal paneller yoktur ve histomorfolojik bulgular halen altın standart olarak kabul edilmektedir. SPINK1, Keratin 17 (KRT17) ve Laminin immün boyalarının neoplastik mesane lezyonlarını ayırt etmedeki potansiyel önemini göstermeyi amaçladık. Gereç ve Yöntem: KRT17, SPINK1 ve Laminin ekspresyonları immünohistokimyal yöntemle, toplam 141 doku örneğinde, neoplastik olmayan mesane mukozası (NBM) ve neoplastik mesane lezyonlarında araştırıldı. Bulgular: KRT17 ve SPINK1 sıklıkla tümör dokularında eksprese edilir (sırasıyla %86,2 ve %68,7). NBM ve yedi neoplastik grubun tümü arasında KRT17 immün boyamasında istatistiksel olarak anlamlı bir fark tespit edildi (p=0.03 ila p0.001). NBM'de SPINK1 ekspresyonu, neoplazmlara kıyasla önemli ölçüde daha düşüktü. KRT17 ile tümör dokusundaki hücrelerin %2,5 veya daha fazlasının boyanması, neoplastik lezyonları neoplastik olmayan lezyonlardan, %86,3 duyarlılık ve %100 özgüllük ile ayırır. Bununla birlikte, tümör dokusundaki hücrelerin %12,5 veya daha fazlasının SPINK1 ile boyanması, neoplastik lezyonları neoplastik olmayan lezyonlardan, %62.6 duyarlılık ve %60 özgüllük ile ayırır. Neoplazmların %60'ında hem KRT17 hem de SPINK1 boyanmış olmasına rağmen, neoplastik hastaların %5,3'ünde ne KRT17 ne de SPINK1 boyanması görülmedi. Sonuç: KRT17, SPINK1 ve Laminin'den oluşan immünohistokimyasal panel, mesane neoplazisinin doğru tanısında morfolojik bulgularla birlikte kullanılabilir.

Keywords:

Bladder, Cancer, Immunohistochemistry, KRT17 SPINK1, TAT1,

PDF

___

1- Nortier JL, Roumeguère T, Schulz WA, et al. Bladder cancer, A genotoxic causal agent recognized. In: Wild CP, Weiderpass E, Stewart BW, eds. World Cancer Report Cancer research for cancer prevention. Lyon: International Agency for Research on Cancer, 2020;439-446.
2- Reuter VE, Algaba F, Amin MB, et al. Non-invasive urothelial lesions. In: Moch H, Humphrey PA, Ulbright TM , Reuter VE, eds. WHO Classification of Tumours of the Urinary System and Male Genital Organs. Lyon: International Agency for Research on Cancer, 2016;99-107.
3- Lopez-Beltran A, Monlironi R. Non-invasive urothelial neoplasms: according to the most recent WHO classification. Eur Urol 2004; 46:170-76.
4- Gonlero P, Gilio A, Fiorito C, et al. Prognostic factors of 'high-grade' Ta bladder cancers according to the WHO 2004 classification: are these equivalent to 'high-risk' non-muscle-invasive bladder cancer? Urol Int 2014; 92: 36-42.
5-Amin MB, Trpkov K, Lopez-Beltran A, et al. Best Practices Recommendations in the Application of Immunohistochemistry in the Bladder Lesions Report From the International Society of Urologic Pathology Consensus Conference. Am J Surg Pathol 2014;38:e20–e34.
6-Wang GP, Xu CS. Pancreatic secretory trypsin inhibitor: More than a trypsin inhibitor. World J Gastrointest Pathophysiol 2010;1:85–90.
7- Shibata T, Ogawa M, Takata N, et al. Distribution of pancreatic secretory trypsin inhibitor in various human tissues and its inactivation inactivation in the gastric mucosa. Res Commun Chem Pathol Pharmacol 1987;55:243– 8.
8- Babu S, Mockler DC, Roa-Peña L, et al.KRT17 Is a Sensitive and Specific Biomarker of Urothelial Neoplasia. Mod Pathol 2019;32:717-724.
9- Yang L, Zhang S, Wang G. KRT17 in disease pathogenesis: from cancer to dermatoses. J Pathol 2019; 247: 158–165.
10- Khanom R, Nguyen CTK, Kayamori K, et al. KRT17 Is Induced in Oral Cancer and Facilitates Tumor Growth. PLoS ONE 2016;11: e0161163.
11-Dasgupta S, Ewing-Graham PC, van Kemenade FJ, et al. Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful histological features and the utility of cytokeratins 13 and 17. Virchows Archiv 2018;473:739–747.
12-Escobar-Hoyos LF, Yang J, Zhu J, et al. KRT17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker. Mod Pathol 2014; 27: 621–630.
13- Mockler D,Escobar-Hoyos LF, Akalin A, et al. KRT17 Is a Prognostic Biomarker in Endocervical Glandular Neoplasia. Am J Clin Pathol 2017;148:264-273.
14- Fernandez-Flores A. CytoKRT17 immunoexpression in actinic keratosis (bowenoid and nonbowenoid) and in Bowen disease. Ann Diagn Pathol 2016; 20:1–6.
15- Merkin RD, Elizabeth A. Vanner EA, et al. KRT17 is overexpressed and predicts poor survival in estrogen receptor– negative/human epidermal growth factor receptor-2–negative breast cancer. Hum Pathol 2017: 62; 23–32.
16- Gaber A, Johansson M, Stenman UH, et al. High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer. Br J Cancer 2009;100: 1540–8.
17-Ozaki N, Ohmuraya M, Hirota M, et al. Serine protease inhibitor Kazal type 1 promotes proliferation of pancreatic cancer cells through the epidermal growth factor receptor. Mol Cancer Res 2009;7:1572–81.
18- Paju A, Vartiainen J, Haglund C, et al. Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: Prognostic study on tissue and serum. Clin Cancer Res 2004;10: 4761–8.
19- Stenman UH. Tumor-associated trypsin inhibitor. Clin Chem 2002; 48:1206 –9.
20- Tomlins SA, Rhodes DR, Yu J, et al. The role of SPINK1 in ETS rearrangement-negative prostate cancers. Cancer Cell 2008;13:519–28.
21-Holah NS, El-Azab DS, Aiad HAES et al. The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions. Appl Immunohistochem Mol Morphol 2017;25:703–711.
22- Hotakainen K, Bjartell A, Sankila A, et al. Differential expression of trypsinogen and tumor-associated trypsin inhibitor (TATI) in bladder cancer. Int J Oncol 2006; 28: 95-101.
23-Liu A, Xue Y, Liu F, et al. Prognostic Value of the Combined Expression of Tumor-Associated Trypsin Inhibitor (TATI) and p53 in Patients With Bladder Cancer Undergoing Radical Cystectomy. Cancer Biomark 2019;26:281-289.
24-Koskensalo S, Hagström J, Louhimo J, et al.Tumour-Associated Trypsin Inhibitor TATI Is a Prognostic Marker in Colorectal Cancer. Oncology 2012;82:234–241.
25-Rink M, Park K, Volkmer BG, et al. Loss of SPINK1 expression is associated with unfavorable outcomes in urothelial carcinoma of the bladder after radical cystectomy. Urol Oncol 2013;31:1716–1724.
26-Timpl R, Rohde H, Robey PG, et al. Laminin – A glycoprotein from basement membranes. J Biol Chem 1979;254:9933-7.
27- Qiu X, Tan H, Fu D, et al. Laminin is over expressed in breast cancer and facilitate cancer cell metastasis. J Can Res Ther 2018;14:S1170-2.
28-Pradhan D, Amin M, Hooda S, et al. Utility of the laminin immunohistochemical stain in distinguishing invasive from noninvasive urothelial carcinoma. J Can Res Ther 2017;13:947-50.