HER2 hyper-expression in urothelial carcinoma of the bladder in a 30 cases study

Objectif. L’objectif de notre étude est d’évaluer l’expression du HER 2 dans le carcinome urothélial de la vessie sur 30 cas sélectionnés parmi une série de 361 cas colligée au service d’anatomie pathologie du CHU de Batna et de comparer nos résultats aux données de la littérature. Matériels et méthodes. Dans notre étude, nous avons évalué la surexpression de l’HER2 par technique immunohistochimique sur 30 cas, en utilisant les mêmes critères d’interprétation que pour le cancer du sein. Les résultats ont été évalués en utilisant le score d’interprétation de l’American Society of Clinical Oncology (l’ASCO), basé sur le pourcentage de cellules marquées, et l'intensité du marquage dans la perspective d'un traitement par le Trastuzumab (Herceptine). Dans notre étude, seul le score 3 + est considéré comme positif. Résultats et discussion. Nous avons constaté qu’aucun cas de tumeurs à faible potentiel de malignité (TFPM) n’a exprimé le HER2, et que 40 % des carcinomes de haut grade (HG) ont exprimé un marquage intense. Une surexpression de HER2 a été retrouvée dans 23,33% de nos échantillons tumoraux. Ce taux est proche de ceux décrits dans la littérature, allant de 23% à 80% avec d’importants écarts qui pourraient être expliqué par plusieurs hypothèses. Les résultats discordants rapportés dans la littérature nécessitent la standardisation des méthodes des laboratoires. Les différentes études démontrent que les décisions et l’algorithme actuellement utilisés dans les cancers du sein sont également adaptables dans les cancers de la vessie. Conclusion. Malgré la taille réduite de notre échantillon, l’expression de l’HER2 est présente surtout dans les carcinomes de haut grade ce qui concorde avec les données de la littérature des grandes séries. Ces résultats peuvent avoir des implications cliniques sur la prise en charge des tumeurs HER2-positifs localement avancées et/ou métastatiques. Ces patients sont donc des candidats potentiels pour la thérapie ciblée anti HER 2 (Herceptine).

Gynecologic organ involvement and incidental gynecologic organ neoplasms in female patients with urothelial carcinoma of the bladder undergoing anterior pelvic exenteration in Rajavithi Hospital

Objective: To evaluate the pathological data of the bladder and gynecologic organs obtained from anterior pelvic exenteration and review the incidence of gynecologic organ involvement and primary gynecologic tumor. Materials and Methods: The clinicopathological data of 70 patients who were diagnosed with bladder transitional cell carcinoma and underwent anterior pelvic exenteration in Rajavithi Hospital between January 2008 and October 2020 were analyzed to examine and determine any correlations. Results: Thirteen (18.5%) patients had gynecologic organ involvement. This consisted of 4 cases (5.7%) involving the uterus, 7 (10%) involving the vagina, 2 (2.8%) involving the ovaries, and 10 (14.2%) involving the cervix. Female patients with gynecologic organ invasion were more likely to have a high pathological T stage (p < 0.001), and have pre-operative hydronephrosis (p = 0.002). From multivariate logistic regression, pre-operative hydronephrosis was associated with increased risk of gynecologic organ invasion (odds ratio 9.57; 95% confidence interval, 1.86 - 49.18; p = 0.007). There were 23 (32%) female patients incidentally diagnosed with benign gynecologic tumors, specifically 16 (22%) cases of myoma uteri, 7 (10%) of adenomyosis and 4 (2.8%) with ovarian cysts. No patient was diagnosed as having primary gynecologic malignancy. Conclusions: The incidence of gynecologic organ involvement in female patients who had undergone anterior pelvic exenteration for urothelial carcinoma of the bladder was 18.5%. Pre-operative hydronephrosis was a risk factor associated with increased risk of gynecologic organ involvement. Information from this study may allow better identification of candidates for gynecologic organ sparing surgery.

Microsatellite Instability Analysis (MSA) for Bladder Cancer: Past History and Future Directions

Microsatellite instability (MSI), the spontaneous loss or gain of nucleotides from repetitive DNA tracts, is a diagnostic phenotype for gastrointestinal, endometrial, colorectal, and bladder cancers; yet a landscape of instability events across a wider variety of cancer types is beginning to be discovered. The epigenetic inactivation of the MLH1 gene is often associated with sporadic MSI cancers. Recent next-generation sequencing (NGS)-based analyses have comprehensively characterized MSI-positive (MSI+) cancers, and several approaches to the detection of the MSI phenotype of tumors using NGS have been developed. Bladder cancer (here we refer to transitional carcinoma of the bladder) is a major cause of morbidity and mortality in the Western world. Cystoscopy, a gold standard for the detection of bladder cancer, is invasive and sometimes carries unwanted complications, while its cost is relatively high. Urine cytology is of limited value due to its low sensitivity, particularly to low-grade tumors. Therefore, over the last two decades, several new “molecular assays” for the diagnosis of urothelial cancer have been developed. Here, we provide an update on the development of a microsatellite instability assay (MSA) and the development of MSA associated with bladder cancers, focusing on findings obtained from urine analysis from bladder cancer patients as compared with individuals without bladder cancer. In our review, based on over 18 publications with approximately 900 sample cohorts, we provide the sensitivity (87% to 90%) and specificity (94% to 98%) of MSA. We also provide a comparative analysis between MSA and other assays, as well as discussing the details of four different FDA-approved assays. We conclude that MSA is a potentially powerful test for bladder cancer detection and may improve the quality of life of bladder cancer patients.

Prognostic Value of Vascular-Expressed PSMA and CD248 in Urothelial Carcinoma of the Bladder

BackgroundUrothelial carcinoma of the bladder (UCB) is a common cancer of the urinary system. Despite substantial improvements in available treatment options, the survival outcome of patients with advanced UCB is unsatisfactory. Therefore, it is necessary to identify new prognostic biomarkers for monitoring and therapy guidance of UCB. In recent years, prostate-specific membrane antigen (PSMA) and CD248 have been identified promising candidate bio7markers.MethodsIn this study, we first examined PSMA and CD248 expression in tissues from 124 patients with UCB using immunohistochemical and immunofluorescent staining. We then analyzed the association between the expression of the two biomarkers and other clinicopathological features and prognosis. Finally, we performed bioinformatic analysis of CD248 and FOLH 1 (PSMA) using the TCGA-BLCA dataset to explore the underlying mechanism of PSMA and CD248 in the progression of UCB.ResultsAmong the 124 cases, PSMA and CD248 were confirmed to be expressed in tumor-associated vessels. Vascular PSMA and CD248 expression levels were associated significantly with several deteriorated clinicopathological features. Furthermore, using univariate and multivariate Cox analyses, high vascular PSMA and CD248 expression levels were observed to be associated significantly with poor prognosis in patients with UCB. As risk factors, both PSMA and CD248 expression showed good performance to predict prognosis. Furthermore, combining these vascular molecules with other clinical risk factors generated a risk score that could promote predictive performance. Bioinformatic analysis showed that both PSMA and CD248 might contribute to angiogenesis and promote further progression of UCB.ConclusionBoth PSMA and CD248 are specifically expressed in the tumor-associated vasculature of UCB. These two molecules might be used as novel prognostic biomarkers and vascular therapeutic targets for UCB.