Collecting duct carcinomas represent a unique tumor entity based on genetic alterations

Frank Becker, Kerstin Junker, Martin Parr, Arndt Hartmann, Susanne Füssel, Marieta Toma, Rainer Grobholz, Thomas Pflugmann, Bernd Wullich, Arne Strauss, Carl Ludwig Behnes, Wolfgang Otto, Michael Stöckle, Volker Jung, Frank Becker, Kerstin Junker, Martin Parr, Arndt Hartmann, Susanne Füssel, Marieta Toma, Rainer Grobholz, Thomas Pflugmann, Bernd Wullich, Arne Strauss, Carl Ludwig Behnes, Wolfgang Otto, Michael Stöckle, Volker Jung

Abstract

Collecting duct carcinoma (CDC) is a rare renal neoplasm that is associated with poor prognosis due to its highly aggressive course and limited response to immuno- or chemotherapy. Histologically, CDC is defined as a subtype of renal cell carcinomas, but in some cases, it is difficult to differentiate from urothelial carcinomas (UC). Therefore the aim of this study was to determine genetic alterations of CDC in comparison to that of urothelial carcinomas of the upper urinary tract (UUT-UC) to clarify the histological origin of this rare tumor entity. Twenty-nine CDC samples were obtained from seven different German centers and compared with twenty-six urothelial carcinomas of the upper urinary tract. Comparative genomic hybridization (CGH) was used to investigate the genetic composition of patients' tumors and allowed the detection of losses and gains of DNA copy numbers throughout the entire genome. The clinical data were correlated with CGH results. CGH analysis of CDC revealed DNA aberrations in many chromosomes. DNA losses were more frequently observed than gains, while high-level amplifications were not detected. The mean frequency of CDC chromosomal aberrations (4.9/case) was slightly lower than that in UUT-UC (5.4/case). Recurrent CDC DNA losses occurred at 8p (n=9/29), 16p (9/29), 1p (n=7/29) and 9p (n=7/29), and gains occurred in 13q (n=9/29). In contrast to CDC, the most frequently detected UUT-UC DNA aberration was a loss at 9q (n=13/26). DNA losses at 9q, 13q and 8q as well as gains at 8p showed significant variations in UUT-UC compared to CDC. There was no correlation between the patients' clinical course and the presence or absence of these recurrent genetic alterations. CDCs are characterized by a different genetic pattern compared to UUT-UC. Regarding the published data on renal cell carcinoma, we conclude that CDC appears to be a unique entity among kidney carcinomas.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Superkaryogram of 29 CDC (A)…
Figure 1. Superkaryogram of 29 CDC (A) and 26 UUT-UC (B) tumors.
Losses of DNA are shown as lines on the left sides of chromosome ideograms, gains on the right side. High-level amplifications (amplicons) are shown as thick bars at the corresponding chromosome regions. Significant differences are highlighted by orange boxes.
Figure 2. Comparison of chromosomal aberrations in…
Figure 2. Comparison of chromosomal aberrations in CDC and UUT-UC tumors in percent.
Losses of chromosomal material are shown on the left side, gains on the right side.

References

    1. Fleming S, Lewi HJ (1986) Collecting duct carcinoma of the kidney. Histopathology 10: 1131-1141. doi:10.1111/j.1365-2559.1986.tb02553.x. PubMed: .
    1. Dimopoulos MA, Logothetis CJ, Markowitz A, Sella A, Amato R et al. (1993) Collecting duct carcinoma of the kidney. Br J Urol 71: 388-391. doi:10.1111/j.1464-410X.1993.tb15978.x. PubMed: .
    1. Kennedy SM, Merino MJ, Linehan WM, Roberts JR, Robertson CN et al. (1990) Collecting duct carcinoma of the kidney. Hum Pathol 21: 449-456. doi:10.1016/0046-8177(90)90209-N. PubMed: .
    1. Carter MD, Tha S, McLoughlin MG, Owen DA (1992) Collecting duct carcinoma of the kidney: a case report and review of the literature. J Urol 147: 1096-1098. PubMed: .
    1. Oudard S, Banu E, Vieillefond A, Fournier L, Priou F et al. (2007) Prospective multicenter phase II study of gemcitabine plus platinum salt for metastatic collecting duct carcinoma: results of a GETUG (Groupe d'Etudes des Tumeurs Uro-Genitales) study. J Urol 177: 1698-1702. doi:10.1016/j.juro.2007.01.063. PubMed: .
    1. Wright JL, Risk MC, Hotaling J, Lin DW (2009) Effect of collecting duct histology on renal cell cancer outcome. J Urol 182: 2595-2599. doi:10.1016/j.juro.2009.08.049. PubMed: .
    1. Abern MR, Tsivian M, Polascik TJ, Coogan CL (2012) Characteristics and outcomes of tumors arising from the distal nephron. Urology 80: 140-146. doi:10.1016/j.urology.2012.03.034. PubMed: .
    1. May M, Ficarra V, Shariat SF, Zigeuner R, Chromecki T et al. (2013) Impact of clinical and histopathological parameters on disease-specific survival in patients with collecting duct renal cell carcinoma - Development of a disease-specific risk-model. J Urol.
    1. Tokuda N, Naito S, Matsuzaki O, Nagashima Y, Ozono S et al. (2006) Collecting duct (Bellini duct) renal cell carcinoma: a nationwide survey in Japan. J Urol 176: 40-43; discussion: 10.1016/S0022-5347(06)00502-7. PubMed: .
    1. Karakiewicz PI, Trinh QD, Rioux-Leclercq N, de la Taille A, Novara G et al. (2007) Collecting duct renal cell carcinoma: a matched analysis of 41 cases. Eur Urol 52: 1140-1145. doi:10.1016/j.eururo.2007.01.070. PubMed: .
    1. Füzesi L, Cober M, Mittermayer C (1992) Collecting duct carcinoma: cytogenetic characterization. Histopathology 21: 155-160. doi:10.1111/j.1365-2559.1992.tb00364.x. PubMed: .
    1. Schoenberg M, Cairns P, Brooks JD, Marshall FF, Epstein JI et al. (1995) Frequent loss of chromosome arms 8p and 13q in collecting duct carcinoma (CDC) of the kidney. Genes Chromosomes Cancer 12: 76-80. doi:10.1002/gcc.2870120115. PubMed: .
    1. Verdorfer I, Culig Z, Hobisch A, Bartsch G, Hittmair A et al. (1998) Characterisation of a collecting duct carcinoma by cytogenetic analysis and comparative genomic hybridisation. Int J Oncol 13: 461-464. PubMed: .
    1. Orsola A, Trias I, Raventós CX, Español I, Cecchini L et al. (2005) Renal collecting (Bellini) duct carcinoma displays similar characteristics to upper tract urothelial cell carcinoma. Urology 65: 49-54. doi:10.1016/j.urology.2004.08.012. PubMed: .
    1. Albadine R, Schultz L, Illei P, Ertoy D, Hicks J et al. (2010) PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. Am J Surg Pathol 34: 965-969. doi:10.1097/PAS.0b013e3181dc5e8a. PubMed: .
    1. Carvalho JC, Thomas DG, McHugh JB, Shah RB, Kunju LP (2012) p63, CK7, PAX8 and INI-1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high-grade tumours of the renal collecting system. Histopathology 60: 597-608. doi:10.1111/j.1365-2559.2011.04093.x. PubMed: .
    1. Kafé H, Verbavatz JM, Cochand-Priollet B, Castagnet P, Vieillefond A (2004) Collecting duct carcinoma: an entity to be redefined? Virchows Arch 445: 637-640. doi:10.1007/s00428-004-1124-z. PubMed: .
    1. Staehler M, Schöppler G, Haseke N, Stadler T, Karl A et al. (2009) Carcinoma of the collecting ducts of Bellini of the kidney: adjuvant chemotherapy followed by multikinase inhibition with sunitinib. Clin Genitourin Cancer 7: 58-61. doi:10.3816/CGC.2009.n.025. PubMed: .
    1. Jung V, Wullich B, Kamradt J, Stockle M, Unteregger G (2007) An improved in vitro model to characterize invasive growing cancer cells simultaneously by function and genetic aberrations. Toxicol In Vitro 21: 183-190. doi:10.1016/j.tiv.2006.09.021.
    1. Jung V, Romeike BF, Henn W, Feiden W, Moringlane JR et al. (1999) Evidence of focal genetic microheterogeneity in glioblastoma multiforme by area-specific CGH on microdissected tumor cells. J Neuropathol Exp Neurol 58: 993-999. doi:10.1097/00005072-199909000-00009. PubMed: .
    1. Singh I, Nabi G (2002) Bellini duct carcinoma: review of diagnosis and management. Int Urol Nephrol 34: 91-95. doi:10.1023/A:1021315130481. PubMed: .
    1. Méjean A, Rouprêt M, Larousserie F, Hopirtean V, Thiounn N et al. (2003) Is there a place for radical nephrectomy in the presence of metastatic collecting duct (Bellini) carcinoma? J Urol 169: 1287-1290. doi:10.1097/01.ju.0000050221.51509.f5. PubMed: .
    1. Parker R, Reeves HM, Sudarshan S, Wolff D, Keane T (2005) Abnormal fluorescence in situ hybridization analysis in collecting duct carcinoma. Urology 66: 1110 PubMed: .
    1. Gregori-Romero MA, Morell-Quadreny L, Llombart-Bosch A (1996) Cytogenetic analysis of three primary Bellini duct carcinomas. Genes Chromosomes Cancer 15: 170-172. doi:10.1002/(SICI)1098-2264(199603)15:3. PubMed: .
    1. Cavazzana AO, Prayer-Galetti T, Tirabosco R, Macciomei MC, Stella M et al. (1996) Bellini duct carcinoma. A clinical and in vitro study. Eur Urol 30: 340-344. PubMed: .
    1. Junker K, Weirich G, Amin MB, Moravek P, Hindermann W et al. (2003) Genetic subtyping of renal cell carcinoma by comparative genomic hybridization. Recent Results Cancer Res 162: 169-175. doi:10.1007/978-3-642-59349-9_15. PubMed: .
    1. Wilhelm M, Veltman JA, Olshen AB, Jain AN, Moore DH et al. (2002) Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer. Cancer Res 62: 957-960. PubMed: .
    1. Marín-Aguilera M, Mengual L, Ribal MJ, Musquera M, Ars E et al. (2007) Utility of fluorescence in situ hybridization as a non-invasive technique in the diagnosis of upper urinary tract urothelial carcinoma. Eur Urol 51: 409-415; discussion: 10.1016/j.eururo.2006.08.045. PubMed: .
    1. Fadl-Elmula I, Gorunova L, Mandahl N, Elfving P, Lundgren R et al. (1999) Cytogenetic analysis of upper urinary tract transitional cell carcinomas. Cancer Genet Cytogenet 115: 123-127. doi:10.1016/S0165-4608(99)00075-8. PubMed: .
    1. Meloni-Ehrig AM (2002) Renal cancer: cytogenetic and molecular genetic aspects. Am J Med Genet 115: 164-172. doi:10.1002/ajmg.10697. PubMed: .
    1. Girgis AH, Iakovlev VV, Beheshti B, Bayani J, Squire JA et al. (2012) Multilevel whole-genome analysis reveals candidate biomarkers in clear cell renal cell carcinoma. Cancer Res 72: 5273-5284. doi:10.1158/1538-7445.AM2012-5273. PubMed: .
    1. Pei J, Feder MM, Al-Saleem T, Liu Z, Liu A et al. (2010) Combined classical cytogenetics and microarray-based genomic copy number analysis reveal frequent 3;5 rearrangements in clear cell renal cell carcinoma. Genes Chromosomes Cancer 49: 610-619. PubMed: .
    1. Dondeti VR, Wubbenhorst B, Lal P, Gordan JD, D'Andrea K et al. (2012) Integrative genomic analyses of sporadic clear cell renal cell carcinoma define disease subtypes and potential new therapeutic targets. Cancer Res 72: 112-121. doi:10.1158/1538-7445.AM2012-112. PubMed: .
    1. Misumi T, Yamamoto Y, Miyachika Y, Eguchi S, Chochi Y et al. (2012) DNA copy number aberrations associated with lymphovascular invasion in upper urinary tract urothelial carcinoma. Cancer Genet 205: 313-318. doi:10.1016/j.cancergen.2012.04.008. PubMed: .

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