Cyclin D1 expression in penile cancer.

The main goal of the present study was to analyze the expression profile of cyclin D1 in patients with PC, and to determine possible correlations with clinical and histopathological features. A survey was conducted with 100 patients diagnosed with PC, who were treated at two reference hospitals in São Luís, Maranhão, Brazil, between 2013 and 2017. A review of clinical, epidemiological, and histopathological data was performed, Human Papillomavírus (HPV) DNA was detected using polymerase chain reaction (PCR) and cyclin D1 expression analysis was performed using immunohistochemical techniques. The data revealed that the absence of cyclin D1 expression was significantly associated with HPV-positive histological subtypes (p = 0.001), while its expression was associated with high-grade tumors (p = 0.014), histological subtype (p = 0.001), presence of sarcomatoid transformation (p = 0.04), and perineural invasion (p = 0.023). Patients with cyclin D1 expression exhibited lower disease-free survival compared to the cyclin D1-negative group, although the difference was not statistically significant. The results suggest that cyclin D1 may be a potential biomarker for PC, especially for poorer prognosis.

What is the Role of SNORA42 in Carcinogenesis? A Systematic Review.

OBJECTIVE: Perform a systematic literature review on SNORA42 in carcinogenesis in order to elucidate its importance, its potential use as a biomarker and as a therapeutic target. METHODS: Using PubMed, SciELO and Science Direct databases as search means, articles that are in line with the scope of the study, written in English, that were published between 2012 and 2022, were selected using the following keywords: "small nucleolar RNA 42", "snoRNA 42" and "SNORA42", as well as searches for the synonyms of this snoRNA (SNORA80E, box H/ACA 42 and ACA42). RESULT: From a total of 131 studies, seven were selected, in which it was possible to identify that SNORA42 interferes in several biological processes, such as proliferation, migration, invasion, metastasis, apoptosis, and signaling pathways. Among the signaling pathways, the p53 and NF-KappaB pathways stand out. Moreover, it is a potential biomarker for diagnosis, prognosis, and treatment of cancer. CONCLUSION: The summary of the main information about SNORA42 in the process of carcinogenesis and cancer progression shows that the use of this snoRNA is ideal for future applications in the field of oncology, in which it can be used as a biomarker and therapeutic target. Thus, it is of fundamental importance to carry out new studies to consolidate the applicability of this molecule.

Aspects of the epidemiological dynamics of acquired syphilis and gestational syphilis between 2010 and 2021 in a state of the northeast region of Brazil / Aspectos da dinâmica epidemiológica da sífilis adquirida e da sífilis gestacional entre 2010 e 2021 em um estado da região nordeste do Brasil / Aspectos de la dinámica epidemiológica de la sífilis adquirida y la sífilis gestacional entre 2010 y 2021 en un estado de la región noreste de Brasil

To characterize the epidemiological dynamics of acquired syphilis and gestational syphilis in the state of Maranhão, between 2010 and 2021. Methods: Confirmed cases of acquired syphilis between 2010 and 2021 and of gestational syphilis between 2010 and 2020, in the state of Maranhão, available by the Sistema de Informação de Agravos de Notificação (SINAN) were analyzed. Results: The year 2018 had the highest number of reports of acquired syphilis (1.787 cases; p < 0.0001). The municipality of Duque Bacelar (East Mesoregion) had the highest incidence rate (285.5 per 100,000 inhabitants), for acquired syphilis, in the triennium 2016 to 2018. Regarding gestational syphilis, the year 2018 also stood out (1,892 cases; p < 0.0001) as the one with the highest number of records. The municipality of Buriticupu (West Mesoregion) had the highest detection rate of gestational syphilis (42.4 per 1,000 live births) in the biennium 2019 and 2020. Conclusions: The data presented showed municipalities with higher rates of acquired syphilis and gestational syphilis, concentrating located respectively in the East and West Mesoregions of the state of Maranhão. The findings obtained in the present study gather useful information for monitoring areas with a high incidence of the disease, thus contributing to the discussion and implementation of effective strategies to reduce cases.

Caracterizar a dinâmica epidemiológica da sífilis adquirida e da sífilis gestacional no Maranhão, entre 2010 e 2021. Métodos: Foram analisados os casos confirmados de sífilis adquirida entre 2010 e 2021 e de sífilis gestacional entre 2010 e 2020, no Maranhão, disponíveis pelo Sistema de Informação de Agravos de Notificação (SINAN). Resultados: O ano de 2018 teve o maior número de notificações de sífilis adquirida (1.787 casos; p < 0,0001). O município de Duque Bacelar (Mesoregião Oriental) teve a maior taxa de incidência (285,5 por 100.000 habitantes), para a sífilis adquirida, no triênio 2016 a 2018. Em relação à sífilis gestacional, o ano de 2018 também se destacou (1.892 casos; p < 0,0001) como o com o maior número de registros. O município de Buriticupu (Mesoregião Ocidental) teve a maior taxa de detecção de sífilis gestacional (42,4 por mil nascidos vivos) no biênio 2019 e 2020. Conclusões: Os dados apresentados mostraram municípios com maiores taxas de sífilis adquirida e sífilis gestacional, concentrando-se localizados respectivamente nas Mesoregiões Leste e Oeste do Estado do Maranhão. Os achados obtidos no presente estudo reúnem informações úteis para o monitoramento de áreas com alta incidência da doença, contribuindo assim para a discussão e implementação de estratégias eficazes para a redução de casos.

Caracterizar la dinámica epidemiológica de la sífilis adquirida y la sífilis gestacional en el estado de Maranhão, entre 2010 y 2021. Métodos: Se analizaron casos confirmados de sífilis adquirida entre 2010 y 2021 y de sífilis gestacional entre 2010 y 2020, en el estado de Maranhão, disponibles por el Sistema de Informação de Agravos de Notificação (SINAN). Resultados: El año 2018 tuvo el mayor número de reportes de sífilis adquirida (1,787 casos; p < 0,0001). El municipio de Duque Bacelar (Mesorregión Este) tuvo la mayor tasa de incidencia (285,5 por 100.000 habitantes), por sífilis adquirida, en el trienio 2016 al 2018. En cuanto a la sífilis gestacional, también se destacó el año 2018 (1.892 casos; p < 0,0001) como el de mayor número de registros. El municipio de Buriticupu (Mesorregión Oeste) tuvo la tasa más alta de detección de sífilis gestacional (42,4 por 1.000 nacidos vivos) en el bienio 2019 y 2020. Conclusiones: Los datos presentados mostraron municipios con mayores tasas de sífilis adquirida y gestacional, concentrándose respectivamente en las Mesorregiones Este y Oeste del estado de Maranhão. Los hallazgos obtenidos en el presente estudio reúnen información útil para el seguimiento de áreas con alta incidencia de la enfermedad, contribuyendo así a la discusión e implementación de estrategias efectivas para disminuir los casos.

A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease.

BACKGROUND: Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão. METHODS: A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67. RESULTS: Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank). CONCLUSIONS: Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.

Non-Coding RNA in Penile Cancer.

Penile cancer (PC) still presents a health threat for developing countries, in particular Brazil. Despite this, little progress has been made on the study of markers, including molecular ones, that can aid in the correct management of the patient, especially concerning lymphadenectomy. As in other neoplasms, non-coding RNAs (ncRNAs) have been investigated for penile cancer, with emphasis on microRNAs, piRNAs (PIWI-interacting small RNAs), and long non-coding RNAs (LncRNAs). In this context, this review aims to assemble the available knowledge on non-coding RNA linked in PC, contributing to our understanding of the penile carcinogenesis process and addressing their clinical relevance. ncRNAs are part of the novel generation of biomarkers, with high potential for diagnosis and prognosis, orientating the type of treatment. Furthermore, its versatility regarding the use of paraffin samples makes it possible to carry out retrospective studies.

Downregulation of miR-145 is associated with perineural invasion in penile carcinoma.

BACKGROUND: Human papillomavirus (HPV) infection is a risk factor for penile cancer (PC). The miR-145 expression has been correlated to this virus genomic amplification. In this context, this work aims to determine the expression level of miR-145 in penile tumors infected by high-risk HPV and correlate it with the clinicopathological characteristics of the tumor and protein expression of p53. METHODS: Formalin-fixed paraffin-embedded from 52 patients with PC, at diagnosis and prior to any cancer treatment, were obtained. HPV identification was performed by nested type PCR, and miR-145 expression was obtained by qRT-PCR. Immunohistochemical analysis of p53 and Ki-67 was performed. RESULTS: Tumoral miR-145 expression was significantly lower compared to adjacent tissue. Additionally, there was a significant reduction of miR-145 expression in invasion perineural, histological associated HPV, and absence of p53 expression in positive HPV cases. HPV infection was detected in 86.5%, the most frequent HPV16. Reduced disease-free survival was observed in patients with low expression of miR-145. CONCLUSIONS: Our data suggest that the underexpression of miR-145 may be triggered by HPV action, decreasing protein expression of p53, and being correlated with perineural invasion. Therefore, the deregulation of miR-145 provides clues as to the potential role in penile carcinogenesis and is also a potential candidate for validation in noninvasive samples.

MIR-107, MIR-223-3P and MIR-21-5P Reveals Potential Biomarkers in Penile Cancer.

BACKGROUND: Inguinal lymph node involvement is the main prognostic factor in patients with penile cancer. However, there is a lack of marker/s for lymph node metastasis. microRNAs have been investigated as potential markers for prognosis of various types of cancer. Taking this into consideration, our main goal was to determine the association of miR-223-3p, miR-107, and miR-21-5p expression with clinicopathological characteristics, as well as presence of lymph node metastasis in patients with penile cancer. METHODS: Formalin-fixed paraffin-embedded penile squamous cell carcinoma specimens from 50 patients, at diagnosis and prior to any cancer treatment, were obtained. Tissue samples comprising at least 70% malignant cells and adjacent non-tumor tissues were evaluated by using qRT-PCR for expression level of miR-223-3p, miR-107 and miR-21-5p. Additionally, molecular identification of HPV was performed by PCR, and the expression levels of PTEN were analyzed by immunohistochemistry. RESULTS: Penile squamous cell carcinoma primary tumors presented higher expression of miR-223-3p, miR-107, and miR-21-5p when compared to non-tumor adjacent tissues. Upregulation of miR-223-3p was associated lymph node metastasis. Higher expression of miR-107 was associated with worsening of prognosis (as observed by histological grade II and III, tumors bigger than 2.0 cm, stage III and IV, and lower disease-free survival). In addition, higher expression of miR-107 and miR-21-5p was correlated to the absence of PTEN protein expression. CONCLUSIONS: Our data demonstrate that higher expression of miR-223-3p, miR-107, and miR-21-5p is correlated with poor prognosis in penile cancer. The upregulation of these microRNAs potentially affect critical cancer pathways and may be important for the prognosis and response to therapy in penile cancer.

Evaluation of diagnosed cases of eye rhinosporidiosis in a public hospital of Maranhão, Northeast Brazil.

BACKGROUND: Oculosporidiosis (ocular rhinosporidiosis) accounts for 15% of cases of rhinosporidiosis, which is a chronic granulomatous disease and is endemic in India and Sri Lanka. In Brazil, the climatic and hydrographic similarities to these endemic areas and the presence of riverside populations contributes to an increase in the incidence of rhinosporidiosis particularly in the State of Maranhão. This study, therefore, aimed to identify the number of diagnosed cases of oculosporidiosis and describe its the clinical epidemiology, laboratory, histopathology, and therapeutic characteristics. METHODS: The study is descriptive, observational, and cross-sectional, and reports the prevalence and clinical epidemiological characteristics of oculosporidiosis in the State of Maranhão, Brazil. A retrospective analysis of the paper and electronic records for a period from 1999 to 2017 was conducted in the University Hospital of Federal University of Maranhão (HU-UFMA), located in the northeastern region of Brazil. RESULTS: Thirty patients were diagnosed with rhinosporidiosis, eight of them had oculosporidiosis and seven of these met the criteria to be included in the study. Of the cases (23.3% of all 30), five were men (71.4%) and two women (28.5%), with an average age of 16.4 ± 15.6 years. In terms of race, four patients (57.1%) declared themselves white and three (42.9%) as brown. The north of the state, the mesoregion, had the most diagnosed cases accounting for 57.1% of the total. Left eye was the most affected site, reported in six patients (85.7%), while the conjunctiva was affected in all patients. Rhinosporidiosis and papilloma were the predominant diagnostic hypotheses (28.5 and 28.5%, respectively), followed by chronic scleritis, granuloma, and chalazion (14.25, 14.25, and 14.25%, respectively). All these cases were treated with lesion excision, and only two patients (28.5%) progressed with recurrence. CONCLUSION: It was verified that there was a male predominance, with only one eye reported as an infected site, with no bilateral involvement. The younger age group (between 1 and 2 years of age) was more affected by oculosporidiosis, and histopathological examination was necessary for a conclusive diagnosis.

P16INK4a expression in patients with penile cancer.

BACKGROUND: Infection with human papillomavirus (HPV) is reported to be present in 30-50% of penile cancer cases. The immunohistochemical test for p16INK4a is used as an indicator of the presence of HPV and as a prognostic marker for squamous cell carcinomas in various sites. However, the role of this marker in penile carcinoma has not yet been completely elucidated. The aim of this study was to analyze whether the expression of p16INK4a is associated with the presence of HPV, histological parameters, and survival in penile cancer. METHODS: A study was conducted from 2014 to 2016 that included 55 patients with penile carcinoma. HPV DNA was detected through PCR using fresh tumor tissue, and immunohistochemistry was performed for analysis of p16INK4a protein using paraffin-embedded tissue. Evaluation of histological parameters was performed following complete embedding of the tumor tissue in paraffin. RESULTS: HPV DNA (low-risk and high-risk genotypes) was found in 49 (89.1%) cases, and 46/49 (93.9%) showed high-oncogenic risk HPV (HR-HPV). Of the 22 cases positive for p16INK4a, HR-HPV DNA was present in 21 (95.5%) (p = 0.032). Regarding histological parameters, p16INK4a and HR-HPV were significantly associated only with tumor subtype (p = 0.036 and p = 0.032, respectively); all carcinomas with basaloid characteristics were positive for p16INK4a. Although HPV+ patients had a higher disease-free survival (p <0.001), p16INK4a expression was not associated with patient survival. CONCLUSIONS: Our study, using fresh tissue samples, showed the highest incidence of HPV compared to that observed in the literature. Expression of the p16INK4a protein was significantly associated with the presence of HR-HPV and this expression may serve as a marker for the presence of the virus. The p16INK4a protein was not associated with the histological prognostic parameters, with the exception of tumor subtype, nor with patient survival. In the results, we showed that the objective of the present study was reached.

Penile cancer in Maranhão, Northeast Brazil: the highest incidence globally?

BACKGROUND: The objectives of this study were to determine the minimum incidence of penile cancer in the poorest Brazilian state, and to describe the epidemiologic and clinical characteristics of patients diagnosed with the disease. METHODS: A retrospective study of 392 patients diagnosed with penile cancer in the three most important referral center in the state was conducted during 2004-2014. RESULTS: The age-standardized incidence was 6.15 per 100,000 and the crude annual incidence was 1.18 per 100,000. More than half (61.1%) of the tumors were histological grades 2 and 3, and 66.4% of tumors were classified as at least stage T2. The average age of patients was 58.6 ± 15.7 years (range, 18 to 103 years), with 20.8% of patients ≤40 years of age at diagnosis. The vast majority underwent penectomy (93%). Only 41.8% underwent lymphadenectomy, 58 patients (14.8%) received chemotherapy, and 54 patients (13.8%) received radiotherapy. Stage 3/4 and vascular invasion were statically significant at disease-free survival analysis. CONCLUSION: The state of Maranhão has the highest incidence of penile cancer in Brazil and globally. Tumors are locally advanced and at the time of diagnosis, and there is a high frequency among young individuals. Patients have a low socioeconomic status, making it difficult to complete treatment and receive appropriate follow-up.

Rhinosporidiosis: the largest case series in Brazil.

INTRODUCTION: Rhinosporidiosis is a chronic infection of the mucous membrane and is caused by Rhinosporidium seeberi, an aquatic mesomycetozoan. The mode of infection is probably transepithelial penetration. The large number of rivers and lakes and the strong presence of riparian populations in the State of Maranhão are strong predisposing factors for rhinosporidiosis. METHODS: A 5-year retrospective study was conducted in a tertiary medical center situated in Maranhão, Northeast Brazil. Twenty-five Maranhense patients diagnosed with rhinosporidiosis were analyzed. RESULTS: Most of the patients were children, adolescents and young adults (age range: 7-24 years, mean age: 14 years). The majority of the participants were male (84%), brown (76%), and students (92%). All lesions involved the entire nasal cavity and presented with a vascular polypoid mass. All patients were treated by surgical excision of the lesions. CONCLUSIONS: Rhinosporidiosis affects younger age groups, especially students from the countryside and the outskirts of urban areas. This study will aid and guide physicians in diagnosing and treating this infection in endemic areas.

Rhinosporidiosis: the largest case series in Brazil

Abstract: INTRODUCTION: Rhinosporidiosis is a chronic infection of the mucous membrane and is caused by Rhinosporidium seeberi, an aquatic mesomycetozoan. The mode of infection is probably transepithelial penetration. The large number of rivers and lakes and the strong presence of riparian populations in the State of Maranhão are strong predisposing factors for rhinosporidiosis. METHODS: A 5-year retrospective study was conducted in a tertiary medical center situated in Maranhão, Northeast Brazil. Twenty-five Maranhense patients diagnosed with rhinosporidiosis were analyzed. RESULTS: Most of the patients were children, adolescents and young adults (age range: 7-24 years, mean age: 14 years). The majority of the participants were male (84%), brown (76%), and students (92%). All lesions involved the entire nasal cavity and presented with a vascular polypoid mass. All patients were treated by surgical excision of the lesions. CONCLUSIONS: Rhinosporidiosis affects younger age groups, especially students from the countryside and the outskirts of urban areas. This study will aid and guide physicians in diagnosing and treating this infection in endemic areas.