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Pathology & Oncology Research

, Volume 24, Issue 3, pp 567–574 | Cite as

High Grade T1 Papillary Urothelial Bladder Cancer Shows Prominent Peritumoral Retraction Clefting

  • Tihana DžombetaEmail author
  • Božo Krušlin
Original Article

Abstract

Differentiation of noninvasive from invasive papillary urothelial carcinoma can be challenging due to inability of proper orientation and thermal damage of transurethrally obtained material. The aim of this study was to analyze the presence and extent of peritumoral retractions in pT1 compared to pTa papillary urothelial carcinoma. Since peritumoral retractions may result from altered expression profiles of extracellular matrix proteins, we additionally analyzed the expression of matrix metalloproteinase 2 (MMP-2) and interleukin 8 (IL-8) in these tumors. The study comprised 50 noninvasive (pTa) and 50 invasive (pT1) cases of transurethrally obtained primary papillary urothelial carcinomas. The invasive nature of nests showing peritumoral retractions was confirmed immunohistochemically using antibody against collagen IV. Staining for MMP-2 and IL-8 was evaluated semiquantitatively using immunohistochemical staining index, calculated by multiplying the percentage of positive cells and staining intensity. Peritumoral retractions were found in 32% of pT1 carcinomas but in none of the pTa carcinomas. All tumors showing peritumoral retraction were high grade tumors. There was no statistically significant correlation between the expression of MMP-2 or IL-8 and the presence of peritumoral retractions or stage of the tumor (pTa vs. pT1). A statistically significant but weak correlation was found between MMP-2 and IL-8 expression (χ2-test, p=0,015). There was no statistically significant correlation between the presence of peritumoral retractions or MMP-2 expression and tumor recurrence and progression. Our study shows that, in doubtful cases, when differentiating between pTa and pT1 stages of papillary urothelial carcinoma, the presence of peritumoral retractions could favor the diagnosis of invasive neoplasm.

Keywords

Urinary bladder Papillary urothelial carcinoma Peritumoral retraction clefting Matrix metalloproteinase 2 Interleukin 8 

Notes

Acknowledgements

This research was supported in part by the University of Zagreb funds for predoctoral fellows. We would like to thank Đurđica Poljan for the help in slide preparation, Milan Milošević for statistical analysis, and Davor Trnski, Davor Tomas and Sven Seiwerth for insightful comments.

Compliance with Ethical Standards

Conflict of Interest

The authors declare they have no conflict of interest.

References

  1. 1.
    Sievert KD, Amend B, Nagele U, Schilling D, Bedke J, Horstmann M, Hennenlotter J, Kruck S, Stenzl A (2009) Economic aspects of bladder cancer: what are the benefits and costs? World J Urol 27:295–300CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tumours of the Urinary System (2004) In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds) World Health Organization classification of Tumours: pathology and genetics of Tumours of the urinary system and male genital organs, 3rd edn. IARC Press, Lyon, pp 90–123Google Scholar
  3. 3.
    Sobin LH, Gospodarowicz MK, Wittekind C (2010) International union against cancer. TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, ChichesterGoogle Scholar
  4. 4.
    Cheng L, Lopez-Beltran A, MacLennan GT, Montironi R, Bostwick DG (2014) Neoplasms of the urinary bladder. In: Bostwick DG, Cheng (eds) urologic surgical pathology, 3rd edn. Elsevier Saunders, Philadelphia, pp 243–268Google Scholar
  5. 5.
    Kruslin B, Tomas D, Rogatsch H, Novosel I, Cupić H, Belicza M, Kraus O, Mikuz G (2003) Periacinar retraction clefting in the prostatic needle core biopsies: an important diagnostic criterion or a simple artifact? Virchows Arch 443:524–527CrossRefPubMedGoogle Scholar
  6. 6.
    Krušlin B, Ulamec M, Tomas D (2015) Prostate cancer stroma: an important factor in cancer growth and progression. Bosn J Basic Med Sci 15:1–7PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Tomas D, Spajić B, Milošević M, Demirović A, Marušić Z, Krušlin B (2011) Extensive retraction artifacts predict biochemical recurrence-free survival in prostatic carcinoma. Histopathology 58:447–454CrossRefPubMedGoogle Scholar
  8. 8.
    Acs G, Dumoff KL, Solin LJ, Pasha T, Xu X, Zhang PJ (2007) Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma. Am J Surg Pathol 31:129–140CrossRefPubMedGoogle Scholar
  9. 9.
    Larsen MP, Steinberg GD, Brendler CB, Epstein JI (1990) Use of Ulex Europaeus agglutinin I (UEAI) to distinguish vascular and "pseudovascular" invasion in transitional cell carcinoma of bladder with lamina propria invasion. Mod Pathol 3:83–88PubMedGoogle Scholar
  10. 10.
    Ramani P, Birch BR, Harland SJ, Parkinson MC (1991) Evaluation of endothelial markers in detecting blood and lymphatic channel invasion in pT1 transitional carcinoma of bladder. Histopathology 19:551–554CrossRefPubMedGoogle Scholar
  11. 11.
    Sangoi AR, Higgins JP, Rouse RV, Schneider AG, McKenney JK (2009) Immunohistochemical comparison of MUC1, CA125, and Her2Neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact. Mod Pathol 22:660–667CrossRefPubMedGoogle Scholar
  12. 12.
    Bonnans C, Chou J, Werb Z (2014) Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15:786–801CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Stamenkovic I (2003) Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 200:448–464CrossRefPubMedGoogle Scholar
  14. 14.
    Wallard MJ, Pennington CJ, Veerakumarasivam A, Burtt G, Mills IG, Warren A, Leung HY, Murphy G, Edwards DR, Neal DE, Kelly JD (2006) Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma. Br J Cancer 94:569–577CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Brew R, Erikson JS, West DC, Kinsella AR, Slavin J, Christmas SE (2000) Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro. Cytokine 12:78–85Google Scholar
  16. 16.
    Li A, Dubey S, Varney ML, Dave BJ, Singh RK (2003) IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol 170:3369–3376Google Scholar
  17. 17.
    Urquidi V, Chang M, Dai Y, Kim J, Wolfson ED, Goodison S, Rosser CJ (2012) IL-8 as a urinary biomarker for the detection of bladder cancer. BMC Urol 12:12CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Rosser CJ, Chang M, Dai Y, Ross S, Mengual L, Alcaraz A, Goodison S (2014) Urinary protein biomarker panel for the detection of recurrent bladder cancer. Cancer Epidemiol Biomark Prev 23:1340–1345CrossRefGoogle Scholar
  19. 19.
    Tumours of the Urinary System (2016) In: Moch H, Humphrey PA, Ulbright TM, Reuter VE (eds) World Health Organization classification of Tumours: pathology and genetics of Tumours of the urinary system and male genital organs, 4th edn. IARC Press, Lyon, pp 78–108Google Scholar
  20. 20.
    Willis DL, Fernandez MI, Dickstein RJ, Parikh S, Shah JB, Pisters LL, Guo CC, Henderson S, Czerniak BA, Grossman HB, Dinney CP, Kamat AM (2015) Clinical outcomes of cT1 micropapillary bladder cancer. J Urol 193:1129–1134CrossRefPubMedGoogle Scholar
  21. 21.
    Krušlin B, Tomas D, Cviko A, Čupić H, Odak L, Belicza M (2006) Periacinar Clefting and p63 immunostaining in prostatic intraepithelial neoplasia and prostatic carcinoma. Pathol Oncol Res 12:205–209CrossRefPubMedGoogle Scholar
  22. 22.
    McKenney JK, Gomez JA, Desai S, Lee MW, Amin MB (2001) Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion. Am J Surg Pathol 25:356–362CrossRefPubMedGoogle Scholar
  23. 23.
    Dotto GP (2014) Multifocal epithelial tumors and field cancerization: stroma as a primary determinant. J Clin Invest 124:1446–1453CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cardiff RD, Borowsky AD (2010) Precancer: sequentially acquired or predetermined? Toxicol Pathol 38:171–179CrossRefPubMedGoogle Scholar
  25. 25.
    van der Horst G, Bos L, van der Pluijm G (2012) Epithelial plasticity, cancer stem cells, and the tumor-supportive stroma in bladder carcinoma. Mol Cancer Res 10:995–1009CrossRefPubMedGoogle Scholar
  26. 26.
    Chaffer CL, Brennan JP, Slavin JL, Blick T, Thompson EW, Williams ED (2006) Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Res 66:11271–11278CrossRefPubMedGoogle Scholar
  27. 27.
    Tomas D, Ulamec M, Hudolin T, Bulimbašić S, Belicza M, Krušlin B (2006) Myofibroblastic stromal reaction and expression of tenascin-C and laminin in prostate cancer. Prostate Cancer Prostatic Dis 9:414–419CrossRefPubMedGoogle Scholar
  28. 28.
    Fávaro WJ, Hetzl AC, Reis LO, Ferreira U, Billis A, Cagnon VH (2012) Periacinar retraction clefting in nonneoplastic and neoplastic prostatic glands: artifact or molecular involvement. Pathol Oncol Res 18:285–292CrossRefPubMedGoogle Scholar
  29. 29.
    Acs G, Khakpour N, Kiluk J, Lee MC, Laronga C (2015) The presence of extensive retraction clefts in invasive breast carcinomas correlates with lymphatic invasion and nodal metastasis and predicts poor outcome: a prospective validation study of 2742 consecutive cases. Am J Surg Pathol 39:325–337CrossRefPubMedGoogle Scholar
  30. 30.
    Hadler-Olsen E, Winberg JO, Uhlin-Hansen L (2013) Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets. Tumour Biol 34:2041–2051CrossRefPubMedGoogle Scholar
  31. 31.
    Eissa S, Ali-Labib R, Swellam M, Bassiony M, Tash F, El-Zayat TM (2007) Noninvasive diagnosis of bladder cancer by detection of matrix metalloproteinases (MMP-2 and MMP-9) and their inhibitor (TIMP-2) in urine. Eur Urol 52:1388–1396CrossRefPubMedGoogle Scholar
  32. 32.
    Roy R, Louis G, Loughlin KR, Wiederschain D, Kilroy SM, Lamb CC, Zurakowski D, Moses MA (2008) Tumor-specific urinary matrix metalloproteinase fingerprinting: identification of high molecular weight urinary matrix metalloproteinase species. Clin Cancer Res 14:6610–6617CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Davies B, Waxman J, Wasan H, Abel P, Williams G, Krausz T, Neal D, Thomas D, Hanby A, Balkwill F (1993) Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res 53:5365–5369PubMedGoogle Scholar
  34. 34.
    Vasala K, Pääkkö P, Turpeenniemi-Hujanen T (2003) Matrix metalloproteinase-2 immunoreactive protein as a prognostic marker in bladder cancer. Urology 62:952–957CrossRefPubMedGoogle Scholar
  35. 35.
    Szarvas T, Becker M, Vom Dorp F, Gethmann C, Tötsch M, Bánkfalvi A, Schmid KW, Romics I, Rübben H, Ergün S (2010) Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer. Cancer Sci 101:1300–1308CrossRefPubMedGoogle Scholar
  36. 36.
    Szarvas T, Jäger T, Becker M, Tschirdewahn S, Niedworok C, Kovalszky I, Rübben H, Ergün S, Vom Dorp F (2011) Validation of circulating MMP-7 level as an independent prognostic marker of poor survival in urinary bladder cancer. Pathol Oncol Res 17:325–332CrossRefPubMedGoogle Scholar
  37. 37.
    Reis ST, Leite KR, Piovesan LF, Pontes-Junior J, Viana NI, Abe DK, Crippa A, Moura CM, Adonias SP, Srougi M, Dall’Oglio MF (2012) Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of bladder cancer. BMC Urol 12:18Google Scholar
  38. 38.
    Xia W, Chen W, Zhang Z, Wu D, Wu P, Chen Z, Li C, Huang J (2015) Prognostic value, clinicopathologic features and diagnostic accuracy of interleukin-8 in colorectal cancer: a meta-analysis. PLoS One 10:e0123484CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Zhang G, Gomes-Giacoia E, Dai Y, Lawton A, Miyake M, Furuya H, Goodison S, Rosser CJ (2014) Validation and clinicopathologic associations of a urine-based bladder cancer biomarker signature. Diagn Pathol 9:200CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  1. 1.Department of Pathology, School of MedicineUniversity of ZagrebZagrebCroatia
  2. 2.Department of PathologyClinical Hospital Centre Sestre milosrdniceZagrebCroatia

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