Bladder carcinoma shows marked pathological heterogeneity, and tissue-based markers may help identify tumors with aggressive pathological features. Data on molecular pathology markers in bladder carcinoma are still limited in African cohorts, including Sudan. This study assessed whether leptin receptor (LEPR) immunohistochemical expression was associated with histological grade, pathological pT category, muscle invasion, and lymphovascular invasion in Sudanese bladder carcinoma. LEPR expression was assessed by immunohistochemistry in 153 archived FFPE urinary bladder carcinoma specimens from four Sudanese institutions and was classified using the immunoreactive score. Urothelial carcinoma predominated in this cohort (136/153, 88.9%). High-grade disease was present in 49/136 urothelial carcinomas (36.0%). Pathological pT category was assessable in 149 cases, with 54/149 tumors (36.2%) classified as pT2 or higher. Muscle invasion was present in 54/149 tumors (36.2%), and lymphovascular invasion was present in 56/149 tumors (37.6%). Moderate LEPR immunoreactivity was more frequent in high-grade than low-grade urothelial carcinomas (28.6% vs 10.3%; p = 0.002). LEPR expression also varied by pT category (p = 0.002), muscle invasion (p = 0.001), and lymphovascular invasion (p = 0.001). Moderate expression was most frequent in pT2-or-higher tumors (35.2%) and was higher in muscle-invasive than non-muscle-invasive tumors (35.2% vs 18.9%). In this Sudanese cohort, higher LEPR expression was observed frequently in tumors with adverse pathological features. Further studies should include matched normal urothelium, outcome data, and adjusted analyses to clarify whether LEPR has biological and prognostic significance.
Jubber, I., Ong, S., Bukavina, L., Black, P.C., Compérat, E., Kamat, A.M., et al. (2023) Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors. European Urology, 84, 176-190. https://doi.org/10.1016/j.eururo.2023.03.029
[3]
Saginala, K., Barsouk, A., Aluru, J.S., Rawla, P., Padala, S.A. and Barsouk, A. (2020) Epidemiology of Bladder Cancer. Medical Sciences, 8, Article 15. https://doi.org/10.3390/medsci8010015
[4]
Tateo, V., Mollica, V., Rizzo, A., Santoni, M. and Massari, F. (2023) Re: WHO Classification of Tumours, 5th Edition, Volume 8: Urinary and Male Genital Tumours. European Urology, 84, 348-349. https://doi.org/10.1016/j.eururo.2023.04.030
[5]
Amin, M.B., Greene, F.L., Edge, S.B., Compton, C.C., Gershenwald, J.E., Brookland, R.K., et al. (2017) The Eighth Edition AJCC Cancer Staging Manual: Continuing to Build a Bridge from a Population-Based to a More “Personalized” Approach to Cancer Staging. CA: A Cancer Journal for Clinicians, 67, 93-99. https://doi.org/10.3322/caac.21388
[6]
Babjuk, M., Burger, M., Compérat, E.M., Gontero, P., Mostafid, A.H., Palou, J., et al. (2019) European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer (TaT1 and Carcinoma in Situ)—2019 Update. European Urology, 76, 639-657. https://doi.org/10.1016/j.eururo.2019.08.016
[7]
Lin, T.C. and Hsiao, M. (2021) Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments. International Journal of Molecular Sciences, 22, Article 2870. https://doi.org/10.3390/ijms22062870
[8]
Ray, A. and Cleary, M.P. (2017) The Potential Role of Leptin in Tumor Invasion and Metastasis. Cytokine & Growth Factor Reviews, 38, 80-97. https://doi.org/10.1016/j.cytogfr.2017.11.002
[9]
Khabaz, M.N., Qureshi, I.A. and Al-Maghrabi, J.A. (2021) Leptin Expression Is Substantially Correlated with Prognosis of Urinary Bladder Carcinoma. Libyan Journal of Medicine, 16, Article 1949798. https://doi.org/10.1080/19932820.2021.1949798
[10]
Kashiwagi, E., Abe, T., Ushijima, M., Shiota, M., Netto, G., Eto, M., et al. (2020) The Role of Adipocytokines and Their Receptors in Bladder Cancer: Expression of Adiponectin or Leptin Is an Independent Prognosticator. European Urology Open Science, 19, e195. https://doi.org/10.1016/s2666-1683(20)32677-x
Ibrahim, A., Khalid, R., Mohager, S. and Fadl-Elmula, I. (2022) Clinical Characteristics of Urinary Bladder Cancer in the Sudan; Evidence of Pathoetiology Changes. The Gulf Journal of Oncology, 1, 16-20.
[13]
Remmele, W. and Stegner, H.E. (1987) Vorschlag zur einheitlichen Definition eines Immunreaktiven Score (IRS) für den immunhistochemischen Ostrogenrezeptor-Nachweis (ER-ICA) im Mammakarzinomgewebe [Recommendation for Uniform Definition of an Immunoreactive Score (IRS) for Immunohistochemical Estrogen Receptor Detection (ER-ICA) in Breast Cancer Tissue]. Der Pathologe, 8, 138-140.
[14]
Budwit-Novotny, D.A., McCarty, K.S., Cox, E.B., Soper, J.T., et al. (1986) Immunohistochemical Analyses of Estrogen Receptor in Endometrial Adenocarcinoma Using a Monoclonal Antibody. Cancer Research, 46, 5419-5542.
[15]
Fedchenko, N. and Reifenrath, J. (2014) Different Approaches for Interpretation and Reporting of Immunohistochemistry Analysis Results in the Bone Tissue—A Review. Diagnostic Pathology, 9, Article 221.
[16]
Kim, H., Kim, M., Kwak, C., Kim, H.H. and Ku, J.H. (2014) Prognostic Significance of Lymphovascular Invasion in Radical Cystectomy on Patients with Bladder Cancer: A Systematic Review and Meta-Analysis. PLOS ONE, 9, e89259. https://doi.org/10.1371/journal.pone.0089259
[17]
Sylvester, R.J., van der Meijden, A.P.M., Oosterlinck, W., Witjes, J.A., Bouffioux, C., Denis, L., et al. (2006) Predicting Recurrence and Progression in Individual Patients with Stage Ta T1 Bladder Cancer Using EORTC Risk Tables: A Combined Analysis of 2596 Patients from Seven EORTC Trials. European Urology, 49, 466-477. https://doi.org/10.1016/j.eururo.2005.12.031
[18]
de Candia, P., Prattichizzo, F., Garavelli, S., Alviggi, C., La Cava, A. and Matarese, G. (2021) The Pleiotropic Roles of Leptin in Metabolism, Immunity, and Cancer. Journal of Experimental Medicine, 218, e20191593. https://doi.org/10.1084/jem.20191593
[19]
Jiménez-Cortegana, C., López-Saavedra, A., Sánchez-Jiménez, F., Pérez-Pérez, A., Casti？eiras, J., Virizuela-Echaburu, J.A., et al. (2021) Leptin, Both Bad and Good Actor in Cancer. Biomolecules, 11, Article 913. https://doi.org/10.3390/biom11060913
