Comparative genomic hybridization shows complex genomic changes of plasmacytoid urothelial carcinoma

Keck, Bastian; Ellmann, Christina; Stoehr, Robert; Weigelt, Katrin; Goebell, Peter J.; Kunath, Frank; Täubert, Helge; Hartmann, Arndt; Wullich, Bernd; Wach, Sven

doi:10.1016/j.urolonc.2014.06.016

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Unlike Kim et al who reported that 50% plasmacytoid carcinoma displayed positive HER2 FISH [35], none of the 13 plasmacytoid/single-cell carcinomas presented positive HER2 FISH. Of note, a comparative genomic hybridization on 25 plasmacytoid urothelial carcinoma revealed gains on chromosome 17q in 88% cases but only 14% showed HER2 amplification [36]. Intratumoral HER2 heterogeneity has been rarely studied in urothelial carcinoma of the bladder.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of urothelial carcinoma standards, HER2 immunohistochemistry in urothelial carcinoma of the bladder was scored according to breast cancer 2007 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines in the majority of studies with complete membranous staining required for 2+ and 3+ immunohistochemistry scores [9-13, 15, 20, 21]. This approach was associated with significant false positive (9.5-52%) and negative rates (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38).5%) suggesting an inadequate immunohistochemistry scoring system [13,15,17,21,22]. Interestingly, guidelines for breast cancer were revised in 2013 [23] to take into account incompletely immunoreactive membranes ("U" shaped), expanding the number of cases with a 2+ score submitted to FISH assay, and it is unknown whether this new scoring system might be effective in urothelial carcinoma.…”

Section: Introductionmentioning

confidence: 99%

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Reappraisal of HER2 status in the spectrum of advanced urothelial carcinoma: a need of guidelines for treatment eligibility

et al. 2018

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Although human epidermal growth factor receptor 2 (HER2) may represent a therapeutic target, its evaluation in urothelial carcinoma of the bladder does not rely on a standardized scoring system by immunohistochemistry or fluorescent in situ hybridization (FISH), as reflected by various methodology in the literature and clinical trials. Our aim was to improve and standardize HER2 amplification detection in bladder cancer. We assessed immunohistochemical criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for breast cancer and investigated intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients with locally advanced urothelial carcinoma of the bladder. Immunohistochemistry was performed on 178 primary tumors and 126 lymph node metastases, eligible cases (moderate/strong, complete/incomplete membrane staining) were assessed by FISH. HER2 overexpression was more frequent with 2013 ASCO/CAP than 2007 ASCO/CAP guidelines (p < 0.0001). The rate of positive HER2 FISH was similar between primary tumor and lymph node metastases (8%). Among positive FISH cases, 48% were associated with moderate/strong incomplete membrane staining that were not scored eligible for FISH by 2007 ASCO/CAP criteria. Among 3+ immunohistochemistry score cases, 67% were associated with HER2-positive FISH. Concordance between primary tumors and matched lymph node metastases was moderate for immunohistochemistry (κ = 0.54 (CI 95%, 0.41-0.67)) and FISH (κ = 0.50 (CI 95%, 0.20-0.79)). HER2-positive FISH was more frequent in micropapillary carcinomas (12%) and carcinoma with squamous differentiation (11%) than in pure conventional carcinoma (6%). Intratumoral heterogeneity for HER2 immunohistochemistry was observed in 7% primary tumor and 6% lymph node metastases; 24% positive HER2 FISH presented intratumoral heterogeneity. Our study suggests that HER2 evaluation should include an immunohistochemistry screening step with eligibility for FISH including incomplete/complete and moderate/strong membrane staining. Spatial or temporal intratumoral heterogeneity prompts to perform evaluation on both tumor and lymph node, and for each histological variant observed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reappraisal of HER2 status in the spectrum of advanced urothelial carcinoma: a need of guidelines for treatment eligibility

et al. 2018

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“…Of note, Keck et al . recently reported that heterozygous deletion of the CDH1 gene (encoding E‐cadherin protein) was observed in 71% of plasmacytoid UC cases, suggesting that this could be the mechanism behind the loss of membranous E‐cadherin in plasmacytoid UC . We examined the expression of CD138, a marker of plasma cells, because prior studies suggested that CD138 expression was one of the characteristic features of plasmacytoid UC .…”

Section: Discussionmentioning

confidence: 99%

Urinary bladder urothelial carcinoma with concurrent plasmacytoid and micropapillary differentiations: A report of two cases with an emphasis on serum carbohydrate antigen 19‐9

Makise

Morikawa

Takeshima

et al. 2015

Pathology International

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We report two cases of urinary bladder urothelial carcinoma (UC). In both, histological examination of a transurethral resection specimen of the bladder tumor revealed UC with plasmacytoid and micropapillary differentiations. In Case 1, residual plasmacytoid UC deeply invaded the extravesical fat tissue of the radical cystectomy specimen, and metastatic carcinoma was found in almost all the dissected lymph nodes. Despite adjuvant chemotherapy and radiotherapy, the patient died 25 months postdiagnosis. Elevated serum carbohydrate antigen 19-9 (CA19-9) returned to near normal levels after radical cystectomy, but they increased shortly before death. In Case 2, no residual carcinoma was found in the radical cystectomy specimen or lymph nodes. Postoperative serum CA19-9 was maintained at normal levels, and the patient remains alive without recurrence or metastasis. Although plasmacytoid and micropapillary UC are known aggressive variants of UC, plasmacytoid UC may be more aggressive. Serum CA19-9 could serve as a useful biomarker to monitor progression of plasmacytoid UC.

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Spezifische Typen des Harnblasenkarzinoms

et al. 2016

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Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review.

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Comparative genomic hybridization shows complex genomic changes of plasmacytoid urothelial carcinoma

Cited by 6 publications

References 26 publications

Reappraisal of HER2 status in the spectrum of advanced urothelial carcinoma: a need of guidelines for treatment eligibility

Reappraisal of HER2 status in the spectrum of advanced urothelial carcinoma: a need of guidelines for treatment eligibility

Urinary bladder urothelial carcinoma with concurrent plasmacytoid and micropapillary differentiations: A report of two cases with an emphasis on serum carbohydrate antigen 19‐9

Spezifische Typen des Harnblasenkarzinoms

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