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Association of current molecular subtypes in urothelial carcinoma with patterns of muscularis propria invasion

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Abstract

Urothelial carcinoma is subdivided into luminal (L), basal (B), and p53-wild-type (WT) molecular subtypes, with basal and p53-WT groups showing more aggressive course and poor treatment response, respectively. The literature on molecular subtypes of UC includes a mixture of different stages. We investigated the molecular profile and outcome of pure cohort of muscle invasive bladder carcinoma (MIBC) considering two distinct patterns of muscularis propria (MP) invasion. Forty-three cystectomies harboring stage pT2 were retrospectively identified in 18 years. MP invasion was subclassified into patterns 1 (tumor encasing intact detrusor muscle bundles) and 2 (tumor dissecting/replacing detrusor muscle). Using IHC, B/L phenotypes, p53, and Ki67 were assessed, and survival data was collected. Pattern 1 invasion was noted in 16 (37%) and pattern 2 in 27 (63%), with mean age of pattern 1 being 10 years younger. B/L phenotypes were successfully determined in 83.7%; 48.8% and 34.8% revealed L and B phenotypes, respectively (indeterminate phenotype in 16.4%). Pattern 1 was associated with L phenotype (GATA3 and HER-2 expressions: p = 0.02 & p = 0.04, respectively). Ki67 ≥ 5/10HPF was noted in pattern 2 and B phenotype (p = 0.03). B phenotype showed association with p53-WT (p = 0.007). In median follow-up of 60.7 months, 63.6% of pattern 1 cases were alive without disease compared to 32% of pattern 2 (not significant). A panel of CK20 and GATA3 for luminal and CK5/6 and CK14 for basal subtypes can provide reliable molecular classification in UC. Also, morphology of MIBC can predict the molecular phenotype and the behavior of the UC.

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Acknowledgements

The authors wish to appreciate the efforts of all colleagues who contributed to this study, including Pallavi Patel, MD; Kara Lombardo; Dongfang Yang, Ashley Sturtevant, and other members of Pathology Research Laboratory in Lifespan/Rhode Island Hospital.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA

    Koorosh Haghayeghi, Shaolei Lu & Ali Amin

  2. Department of Pathology and Laboratory Medicine, The Johns Hopkins Hospital, Baltimore, MD, 21287, USA

    Andres Matoso

  3. Brown Urology, 195 Collyer St. Ste 201, Providence, RI, 02904, USA

    Stephen F. Schiff

  4. Department of Oncology and Minimally Invasive Urology Institute (MIUI), The Miriam Hospital and Lifespan Medical Center, Providence, RI, 02903, USA

    Catrina Mueller-Leonhard

  5. Department of Pathology and Laboratory Medicine, The Miriam Hospital, 164 Summit Ave, Providence, RI, 02906, USA

    Ali Amin

Authors
  1. Koorosh Haghayeghi
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  2. Shaolei Lu
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  4. Stephen F. Schiff
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  5. Catrina Mueller-Leonhard
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Contributions

Dr. Haghayeghi gathered the preliminary immunohistochemical data and provided the preliminary manuscript draft and data. Drs. Lu and Leonhard conducted statistical analysis of the study; Drs. Andres Matoso, Schiff, and Amin were involved in data interpretation, analysis of study findings, and review of the manuscript. Dr Amin also oversaw immunohistochemical interpretation and revisions of the manuscript.

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Correspondence to Ali Amin.

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The authors declare no competing interests.

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The abstract of this study was presented at the 109th United States and Canadian Academy of Pathology (USCAP) Meeting.

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Haghayeghi, K., Lu, S., Matoso, A. et al. Association of current molecular subtypes in urothelial carcinoma with patterns of muscularis propria invasion. Virchows Arch 479, 515–521 (2021). https://doi.org/10.1007/s00428-021-03145-y

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  • DOI: https://doi.org/10.1007/s00428-021-03145-y

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