Publications by authors named "Stephania Martins Bezerra"

13 Publications

  • Page 1 of 1

Single Adrenal Metastasis From Prostate Cancer Detected by 68Ga-PSMA PET/CT and Confirmed by Biopsy: A Case Report.

Clin Nucl Med 2021 Jul 26. Epub 2021 Jul 26.

From the Departments of Nuclear Medicine Clinical Oncology Pathologic Anatomy, A.C.Camargo Cancer Center, São Paulo, Brazil.

Abstract: This image demonstrates an unusual presentation of an adrenal metastasis from prostate cancer detected by 68Ga-prostate-specific membrane antigen PET/CT and confirmed by biopsy. A 68-year-old man with prostate cancer persisted with elevated levels of prostate-specific antigen after radical prostatectomy. Imaging identified a single abnormal uptake in the left adrenal gland. A biopsy was performed showing a metastatic prostatic adenocarcinoma. The patient received systemic treatment, and his prostate-specific antigen level decreased significantly. Our objective is to illustrate an unusual and single site of prostate cancer metastasis, in which precise histological diagnosis was essential for correct clinical management of the patient.
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http://dx.doi.org/10.1097/RLU.0000000000003829DOI Listing
July 2021

Prognostic Impact of Loss of SETD2 in Clear Cell Renal Cell Carcinoma.

Clin Genitourin Cancer 2021 08 17;19(4):339-345. Epub 2021 Mar 17.

Division of Urology, A.C. Camargo Cancer Center, São Paulo, Brazil; National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil.

Purpose: To evaluate the prognostic impact of immunohistochemical expression of SETD2 in patients with clear cell renal cell carcinoma (ccRCC).

Patients And Methods: A total of 662 patients with primary or metastatic ccRCC were evaluated. Two genitourinary pathologist reviewed all of the cases for uniform reclassification and determined the selection of the most representative tumor areas for construction of the tissue microarray (TMA).

Results: SETD2 nuclear staining showed that 101 areas (15.3%) had negative expression, and 561 areas (84,7%) had positive expression of SETD2. The protein expression of SETD2 was associated with clinical stage (P < .001), pathological stage (P < .001), tumor size (P < .001), perinephric fat invasion (P < .001), Eastern Cooperative Oncology Group status (P = .004), surgery type (P < .001), International Society of Urologic Pathologists grade (P < .001), and tumor necrosis (P < .001). SETD2 influenced disease-specific survival (DSS) and overall survival (OS). DSS rates in patients with positive and negative expression of SETD2 were 90.2% and 58.4%, respectively (P < .001). OS rates in patients with positive and negative expression of SETD2 were 87% and 55.4%, respectively (P < .001). In a multivariate Cox analysis, low SETD2 expression was an independent predictor of DSS (hazard ratio [HR], 1.690; 95% confidence interval [CI], 1.0582.700; P = .031) and OS (HR, 1.641; 95% CI, 1.039-2.593; P = .037).

Conclusion: Our study showed that the negative expression of SETD2 was associated with a worse prognosis, and it was an independent predictor of survival in patients with ccRCC. We believe that the protein expression of SETD2 is an important biomarker in the management of patients with ccRCC.
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http://dx.doi.org/10.1016/j.clgc.2021.03.003DOI Listing
August 2021

Annexin A1 promotes the nuclear localization of the epidermal growth factor receptor in castration-resistant prostate cancer.

Int J Biochem Cell Biol 2020 10 25;127:105838. Epub 2020 Aug 25.

Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas, MG, 387400-128, Brazil; Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, MG, 38400-902, Brazil. Electronic address:

Epidermal growth factor receptor is a cancer driver whose nuclear localization has been associated with the progression of prostate cancer to the castration-resistant phenotype. Previous reports indicated a functional interaction between this receptor and the protein Annexin A1, which has also been associated with aggressive tumors. The molecular pathogenesis of castration-resistant prostate cancer remains largely unresolved, and herein we have demonstrated the correlation between the expression levels and localization of the epidermal growth factor receptor and Annexin A1 in prostate cancer samples and cell lines. Interestingly, a higher expression of both proteins was detected in castration-resistant prostate cancer cell lines and the strongest correlation was seen at the nuclear level. We verified that Annexin A1 interacts with the epidermal growth factor receptor, and by using prostate cancer cell lines knocked down for Annexin A1, we succeeded in demonstrating that Annexin A1 promotes the nuclear localization of epidermal growth factor receptor. Finally, we showed that Annexin A1 activates an autocrine signaling in castration-resistant prostate cells through the formyl peptide receptor 1. The inhibition of such signaling by Cyclosporin H inhibits the nuclear localization of epidermal growth factor receptor and its downstream signaling. The present work sheds light on the functional interaction between nuclear epidermal growth factor receptor and nuclear Annexin A1 in castration-resistant prostate cancer. Therefore, strategies to inhibit the nuclear localization of epidermal growth factor receptor through the suppression of the Annexin A1 autocrine loop could represent an important intervention strategy for castration-resistant prostate cancer.
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http://dx.doi.org/10.1016/j.biocel.2020.105838DOI Listing
October 2020

Immunohistochemical negative expression of ezrin predicts poor prognosis in clear cell renal cell carcinoma.

Urol Oncol 2020 03 22;38(3):75.e1-75.e7. Epub 2019 Oct 22.

Urology Division, A.C. Camargo Cancer Center, São Paulo, Brazil; Researches of INCiTO-INOTE Institute, Brazil.

Purpose: To analyze the immunohistochemical expression of ezrin and moesin in clear cell renal cell carcinoma (ccRCC). These proteins, as part of the ezrin-radixin-moesin complex link the cell membrane to the actin cytoskeleton, affecting such processes as cell adhesion, cell survival, cell motility, and signal transduction. Our aim was to examine the impact of their expression on clinical outcomes and survival rates.

Patients And Methods: Five hundred seventy-five consecutive patients who had been treated surgically for ccRCC in a single center between 1985 and 2016 were selected. A single pathologist reviewed all cases to perform a uniform reclassification and determined the most representative tumor areas for construction of a tissue microarray.

Results: Of all ccRCC specimens, 106 (18.3%) were negative for ezrin, and 469 (81.7%) had positive ezrin expression; 16 (2.8%) were negative and 559 (97.2%) were positive for moesin, respectively. Ezrin expression was associated with pT stage (P < 0.001), clinical stage (P = 0.012), synchronic metastasis (P < 0.001), incidental tumors (P = 0.007), and International Society of Urological Pathology histological grade (P = 0.025). There was a correlation between moesin expression and clinical stage (P = 0.027), pT stage (P = 0.025), and pN stage (P = 0.007). Ezrin expression significantly influenced tumor-related deaths. By multivariate analysis, negative ezrin expression was an independent risk factor for disease-specific survival (HR 1.89; 95% CI 1.11-3.20).

Conclusions: Negativity for ezrin in ccRCC patients significantly impacts survival rates. We encourage further prospective studies to analyze ezrin analysis to evaluate its significance in the prognosis of ccRCC.
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http://dx.doi.org/10.1016/j.urolonc.2019.09.011DOI Listing
March 2020

Immunohistochemical expression of renin is a prognostic factor for recurrence in nonmetastatic renal cell carcinoma.

Urol Oncol 2019 12 28;37(12):947-954. Epub 2019 Aug 28.

Department of Pelvic Surgery, Division of Urology, AC Camargo Cancer Center, São Paulo, São Paulo, Brazil; National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, AC Camargo Cancer Center, São Paulo, São Paulo, Brazil.

Purpose: To analyze the intratumoral immunohistochemical expression of renin and its value as a prognostic factor for recurrence in nonmetastatic clear cell renal cell carcinoma (ccRCC).

Methods: A total of 498 patients with nonmetastatic ccRCC from the Latin American Renal Cancer Group database who underwent partial or radical nephrectomy between 1990 and 2016 were selected. All cases were revised, and 2 distinct samples were obtained for tissue microarray construction. Ten years of follow-up was assessed, and disease-free survival rates (DFS) were analyzed. Renin expression was classified qualitatively as negative or positive. For the quantitative analysis, a cutoff was estimated using the maximum of the standardized log-rank statistic.

Results: Nuclear renin was qualitatively positive in 360 cases (72%) and negative in 138 (28%), whereas quantitatively, an equal number of cases had ≤35% or >35% renin-positive nuclei. The absence of renin expression was associated with high-grade tumors (by ISUP and Fuhrman classification, both P < 0.001), greater microscopic venous invasion (P = 0.046), and renal vein invasion (P = 0.026). In the multivariate analyses, qualitatively negative renin expression was an unfavorable prognostic factor for DFS (RR = 2.923, P < 0.001). With regard to quantitative renin expression, a cutoff of ≤35 was associated with worse DFS (RR = 4.085, P < 0.001).

Conclusions: The intratumoral immunohistochemical expression of renin in patients with ccRCC provides valuable prognostic data regarding the likelihood of recurrence.
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http://dx.doi.org/10.1016/j.urolonc.2019.07.012DOI Listing
December 2019

Incidence and distribution of UroSEEK gene panel in a multi-institutional cohort of bladder urothelial carcinoma.

Mod Pathol 2019 10 25;32(10):1544-1550. Epub 2019 Apr 25.

Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA.

Noninvasive approaches for early detection of bladder cancer are actively being investigated. We recently developed a urine- based molecular assay for the detection and surveillance of bladder neoplasms (UroSEEK). UroSEEK is designed to detect alterations in 11 genes that include most common genetic alterations in bladder cancer. In this study, we analyzed 527 cases, including 373 noninvasive and 154 invasive urothelial carcinomas of bladder from transurethral resections or cystectomies performed at four institutions (1991-2016). Two different mutational analysis assays of a representative tumor area were performed: first, a singleplex PCR assay for evaluation of the TERT promoter region (TERTSeqS) and second, a multiplex PCR assay using primers designed to amplify regions of interest of 10 (FGFR3, PIK3CA, TP53, HRAS, KRAS, ERBB2, CDKN2A, MET, MLL, and VHL) genes (UroSeqS). Overall, 92% of all bladder tumors were positive for at least one genetic alteration in the UroSEEK panel. We found TERT promoter mutations in 77% of low-grade noninvasive papillary carcinomas, with a relatively lower incidence of 65% in high-grade noninvasive papillary carcinomas and carcinomas in situ; p = 0.017. Seventy-two percent of pT1 and 63% of muscle-invasive bladder tumors harbored TERT promoter mutations with g.1295228C>T alteration being the most common in all groups. FGFR3 and PIK3CA mutations were more frequent in low-grade noninvasive papillary carcinomas compared with high-grade noninvasive papillary carcinomas and carcinomas in situ (p < 0.0001), while the opposite was true for TP53 (p < 0.0001). Significantly higher rates of TP53 and CDKN2A mutation rates (p = 0.005 and 0.035, respectively) were encountered in muscle-invasive bladder tumors compared with those of pT1 stage. The overwhelming majority of all investigated tumors showed at least one mutation among UroSEEK assay genes, confirming the comprehensive coverage of the panel and supporting its potential utility as a noninvasive urine-based assay.
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http://dx.doi.org/10.1038/s41379-019-0276-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872189PMC
October 2019

Expanding morphological and clinical aspects of hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a case report in a patient with unusual morphology and clinical presentation.

Virchows Arch 2018 Dec 31;473(6):775-779. Epub 2018 Aug 31.

Department of Pathology, AC Camargo Cancer Center, Rua Professor Antônio Prudente 211, São Paulo, 01509-900, Brazil.

Renal cell carcinoma (RCC) accounts for 2-3% of all malignant disease in adults. Hereditary RCC represents 5 to 8% of kidney tumors. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) represents an autosomal dominant syndrome that results from a germline mutation in fumarate hydratase gene (FH). HLRCC patients typically present with skin or uterine leiomyomas and renal neoplasms. HLRCC was recently recognized as a distinct renal tumor subtype by the WHO 2016 classification. Many morphological patterns such as papillary, solid, tubular, and cystic had been described as part of morphological aspects of HLRCC. In this study, we describe a case of a patient that had a history of persistence of ductus arteriosus (PDA) and cryptorchidism. In addition, the renal tumor showed a very unusual hystiocytoid morphological aspect. We confirmed the presence of a FH germline mutation both in the patient and his mother.
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http://dx.doi.org/10.1007/s00428-018-2420-3DOI Listing
December 2018

Breast implant-associated anaplastic large cell lymphoma in a Li-FRAUMENI patient: a case report.

Diagn Pathol 2018 Jan 25;13(1):10. Epub 2018 Jan 25.

Department of Anatomic Pathology, A.C. Camargo Cancer Center, 211 Professor Antônio Prudente Street, Sao Paulo, Zip code 01509-900, Brazil.

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare malignancy, recently recognized as a provisional entity by the World Health Organization. Although increasing data have been published on this entity in recent years, a great number of patients and health professionals remain unaware of this diagnosis.

Case Presentation: We herein report the case of a 56-year-old female with Li-FRAUMENI syndrome who presented with late right-sided recurrent breast swelling after prophylactic adenomastectomy with implant reconstruction. Imaging scans revealed an heterogeneous mass adjacent to the implant fibrous capsule. A biopsy of the lesion rendered the diagnosis of a BIA-ALCL.

Conclusions: This case presents similarities with previous reports, but also some particularities, which should be stressed in order to make the diagnosis the earliest possible. The most distinct feature is that this is the second report of BIA-ALCL arising in the setting of Li-FRAUMENI syndrome.
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http://dx.doi.org/10.1186/s13000-018-0688-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784673PMC
January 2018

Intramammary sentinel lymph node with capsular extravasation in breast cancer.

Ann Surg Treat Res 2017 May 27;92(5):376-379. Epub 2017 Apr 27.

Department of Breast Surgery, AC Camargo Cancer Center, São Paulo, Brazil.

Sentinel lymph node biopsy has been developed as the standard of treatment in breast cancer. Status of axillary sentinel lymph node is known to be a significant prognostic factor. Nevertheless, involvement of an intramammary lymph node with metastasis in breast cancer is a rare radiological and clinical presentation, and with extracapsular extravasation even more uncommon. Historically, reported series of patients with intramammary lymph node diagnosed by final histological examination are small in number and clinical significance of metastasis is still unclear. Here, we report a case of conservative breast cancer surgery with 3 intramammary sentinel lymph nodes containing metastasis and extracapsular extravasation. After multidisciplinary consensus, the patient was surgically reapproached with mastectomy. Even though the 3 intramammary sentinel lymph nodes were positive for metastases, pathology examination did not reveal any signs of malignancy in the mastectomy specimen.
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http://dx.doi.org/10.4174/astr.2017.92.5.376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416920PMC
May 2017

Trilateral retinoblastoma with unilateral eye involvement.

Rev Assoc Med Bras (1992) 2015 Aug;61(4):308-10

Department of Pathology, Hospital A.C.Camargo, São Paulo, SP, BR.

Retinoblastomas (RB) are the main forms of intraocular tumor in childhood, with a worldwide incidence of 1 case per 15,000 to 20,000 live births. Trilateral RB (RBT) is a rare combination of unilateral or bilateral RB with a midline intracranial neoplasm of neuroblastic origin, usually found in the pineal region or the suprasellar region, presenting variable incidence of 0.5% up to 6% among patients with RB. The article reports a case of unilateral RBT in a patient treated at Hospital A.C.Camargo.
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http://dx.doi.org/10.1590/1806-9282.61.04.308DOI Listing
August 2015

Radical prostatectomy and positive surgical margins: relationship with prostate cancer outcome.

Int Braz J Urol 2014 May-Jun;40(3):306-15

2 Division of Urology, Fundação Antonio Prudente A. C. Camargo Cancer Center, São Paulo - SP, Brazil.

Introduction: Positive surgical margins (PSMs) are an adverse factor that may predict a worse outcome in patients submitted to radical prostatectomy (RP). However, not all of these cases will evolve to biochemical (BCR) or clinical (CR) recurrence, therefore relationship between PSMs and these recurrent events has to be correlated with other clinical and pathologic findings to indicate complementary treatment for selected patients.

Materials And Methods: Of 1250 patients submitted to open retropubic radical prostatectomy (RRP), between March 1991 and June 2008, the outcome of 161 patients with PSMs and of 67 without PSMs as a control group, comprising a total of 228 cases were retrospectively reviewed. A minimum follow-up time of 2 years after surgery was considered. BCR was determined when PSA ≥ 0.2 ng/mL. CR was determined whenever there was clinical evidence of tumor. Chi-square test was used to correlate clinical and pathologic variables with PSMs. Time interval to biochemical recurrence was analyzed by the Kaplan-Meier product limit analysis using the log-rank test for comparison between groups. Univariate and multivariate Cox stepwise logistic regression models were used to identify significant predictors of risk of shorter intervals to BCR.

Results: Prostate circumference margin was the most common site with 78 cases (48.44%). Regarding the outcome of 228 cases from both groups, BCR occurred in 68 patients (29.82%), and CR in 10 (4.38%). Univariate analysis showed statistically significant associations (p < 0.001) between presence of PSMs with BCR, but not with CR (p = 0.05). At follow-up of the 161 patients with PSMs, only 61(37.8%) presented BCR, while 100 (62.8%) did not. BCR correlated with pathologic stage; Gleason score; preoperative PSA; tumor volume in the specimen; capsular and perineural invasion; presence and number of PSMs. CR correlated only with angiolymphatic invasion and Gleason score. Considering univariate analysis of clinical and pathologic factors predicting progression-free survival at 5 years, prostate weight; preoperative PSA; Gleason score; pathologic stage; tumor volume; PSMs; capsular and perineural invasion were correlated with BCR. At multivariate analysis, only Gleason score and percentage of tumor volume correlated as significant independent predictors of BCR.

Conclusion: At univariate analysis, presence, number and location of PSMs have consistent correlation with BCR after RRP, but at follow-up BCR occurred only in 37.8% of patients with PSMs. However at multivariate analysis, the significant risk factors for BCR were percentage of tumor volume (p = 0.022) and Gleason score (p < 0.005) in the surgical specimen. Angiolymphatic invasion and Gleason score were significantly correlated with CR.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2014.03.03DOI Listing
February 2015

GATA3 expression in small cell carcinoma of bladder and prostate and its potential role in determining primary tumor origin.

Hum Pathol 2014 Aug 24;45(8):1682-7. Epub 2014 Apr 24.

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231; Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231; Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231. Electronic address:

GATA3 is a sensitive marker for urothelial carcinoma. We here evaluate, for the first time, GATA3 expression in small cell carcinoma of bladder and prostate and assess its utility in the differential diagnosis with small cell carcinoma of lung primary. Archival tissues from 60 small cell carcinomas (12 bladder, 15 lung, and 33 prostate primary cases) were used to build 2 tissue microarrays. We also assessed whole slide sections from 10 additional primary small cell carcinomas of bladder. GATA3 nuclear expression was evaluated using standard immunohistochemistry. Intensity (weak, moderate, and strong) and extent of expression were assessed in each tissue microarray spot. Extent positivity was categorized as focal (1%-25%), multifocal (>25%), and diffuse (>75%). Nuclear GATA3 expression was encountered in 7 bladder (7/22, 32%) and 2 lung (2/15, 13%) small cell carcinomas. All 33 primary prostate small cell carcinomas were negative. Among bladder tumors, strong and diffuse (>75%) GATA3 labeling was seen in 3 cases (3/22, 14%); focal positivity was observed in the 4 remaining cases (4/22, 18%). Both positive lung cases had only focal positivity. Our study is the first to reveal GATA3 expression in the small subset of lung small cell carcinoma that should be taken into consideration in assigning site of origin in advanced small cell carcinoma cases. Our novel finding of GATA3 positivity in one-third of bladder small cell carcinoma is of potential value in differentiating small cell carcinomas of prostate origin from those of bladder origin.
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http://dx.doi.org/10.1016/j.humpath.2014.04.011DOI Listing
August 2014

Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder.

Hum Pathol 2013 Apr 17;44(4):612-22. Epub 2012 Oct 17.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Plasmacytoid urothelial carcinoma is a rare but aggressive variant of bladder cancer with no clear therapeutic guidelines. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been linked to oncogenesis in conventional bladder cancer. Several antineoplastic agents targeting mTOR pathway are currently available. This study assesses mTOR pathway status as well as c-myc and p27 expression. We retrieved 19 archival cases of plasmacytoid urothelial carcinoma from two institutions. Whole tissue sections were evaluated for immunoexpression of phosphatase and tensin homolog (PTEN), phosphorylated mTOR, phosphorylated protein kinase B (AKT), phosphorylated S6, c-myc, and p27. We evaluated intensity (0 to 3+) and extent (0%-100%) of expression for all markers. An H score was calculated as the sum of products of intensity and extent for each marker and used during analysis. In addition, PTEN loss was defined as absence of expression in >10% of tumor cells. We encountered PTEN loss in 28%. Higher H score for nuclear phosphorylated AKT and a lower H score for phosphorylated S6 was encountered in muscle invasive tumors compared to non-muscle invasive tumors (P = .007 and P = .009, respectively). Although a trend for negative prognostic impact on overall survival for higher phosphorylated mTOR expression was noted (P = .051), markers expression levels failed to predict survival in our cohort. We found dysregulation of mTOR pathway members in urinary bladder plasmacytoid urothelial carcinoma, suggesting that the use of mTOR pathway inhibitors might be beneficial for patients with this aggressive tumor.
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http://dx.doi.org/10.1016/j.humpath.2012.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742093PMC
April 2013
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