RESUMO
The study aimed to evaluate grade migration and prognosis depending on pathologic features in patients with prostate cancer treated with radical external beam radiotherapy. The study included 139 patients with an initial Gleason score of 7 (3+4 or 4+3) i.e., Grade Group 2-3 (GG2-GG3) treated between 2008 and 2013. The clinical outcome was assessed with respect to biochemical control (BC) and biochemical disease-free survival (bDFS). After re-evaluation, the majority of patients (96 patients - 69%) were up-graded from GG2-3. Finally, there were 4 patients (3%) with grade GG1, 12 patients (9%) - GG2, 27 patients (19%) - GG3, 51 patients (37%) - GG4 and 45 patients (32%) - GG5. In 42 patients (30%) a cribriform pattern was observed. Among the analyzed factors only the GGs were important for BC (p = 0.011) and the cribriform pattern was of borderline significance (p = 0.06). The 5-year biochemical control was 100% in GG1-3 and 84% in GG4-5. The 5-year biochemical control was 81% and 93%, if cribriform or no cribriform pattern was detected, respectively. In conclusion, re-evaluation and verification of pathology specimens in accordance with contemporary rules upgraded the Gleason score in the majority of patients. The aggressive behavior of prostate cancer starts to occur from GG 4. Cribriform pattern almost tripled the biochemical failure rate.
Assuntos
Prostatectomia , Neoplasias da Próstata , Intervalo Livre de Doença , Humanos , Masculino , Gradação de Tumores , Prognóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapiaRESUMO
BACKGROUND: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. METHODS: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. RESULTS: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. CONCLUSIONS: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.
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The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.
Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Adulto , Humanos , Polônia , Qualidade de Vida , Sociedades Científicas , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodosRESUMO
Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.
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Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Polônia/epidemiologia , Vigilância em Saúde Pública , Sistema de Registros , Fatores Sexuais , Neoplasias Cutâneas/etiologia , Adulto JovemRESUMO
Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer that shares the characteristic features of both basal and squamous cell carcinomas (BCC, SCC). Our research enables better characterization of BSC in comparison to high-risk subtypes of BCC and SCC. Paper includes a retrospective analysis of BSC cases regarding sex, age, number of tumors and anatomical distribution in comparison to BCC and SCC evaluating the differences and defining the implications. Histologically confirmed carcinomas recorded between 1999 and 2019 were studied. 181 diagnosed BSC cases were identified, making this study the largest cohorts of BSC patients reported worldwide. Most cases were reported on head and neck. Analysis of facial anatomic distribution shows that most commonly affected sites were the nose (43%) and the cheek (25%). The age at excision of metatypical BCC was higher than those of low-risk BCC (P < 0.05), however similar to high-risk BCC (P = 0.20). We revisited that the concept of BSC is the most similar to high-risk subtypes of BCC. Patients with diagnosed BSC have higher risk of second nonmelanoma skin cancer. Therefore, the frequency of follow-up examination should be adjusted to the individual risk of another skin cancer.
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Carcinoma Basocelular/epidemiologia , Carcinoma Basoescamoso/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Cutâneas/epidemiologia , Idoso , Carcinoma Basocelular/patologia , Carcinoma Basoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Risco , Neoplasias Cutâneas/patologiaRESUMO
Oxidative stress (OS) is recognized as disturbance of cellular equilibrium between reactive oxygen species (ROS) formation and their elimination by antioxidant defense systems. One example of ROS-mediated damage is generation of potentially mutagenic DNA precursor, 8-oxodGTP. In human cells genomic 8-oxodGTP incorporation is prevented by the MutT homologue 1 (MTH1 or hMTH1 for human MTH1) protein. It is well established that malignant cells, including thyroid cancer cells, require hMTH1 for maintaining proliferation and cancerous transformation phenotype. Above observations led to the development of hMTH1 inhibitors as novel anticancer therapeutics. In the current study we present extensive analysis of oxidative stress responses determining sensitivity to hMTH1 deficiency in cultured thyroid cells. We observe here that hMTH1 depletion results in downregulation of several glutathione-dependent OS defense system factors, including GPX1 and GCLM, making some of the tested thyroid cell lines highly dependent on glutathione levels. This is evidenced by the increased ROS burden and enhanced proliferation defect after combination of hMTH1 siRNA and glutathione synthesis inhibition. Moreover, due to the lack of data on hMTH1 expression in human thyroid tumor specimens we decided to perform detailed analysis of hMTH1 expression in thyroid tumor and peri-tumoral tissues from human patients. Our results allow us to propose here that anticancer activity of hMTH1 suppression may be boosted by combination with agents modulating glutathione pool, but further studies are necessary to precisely identify backgrounds susceptible to such combination treatment.
Assuntos
Dano ao DNA , Enzimas Reparadoras do DNA/metabolismo , Regulação da Expressão Gênica , Glutationa Peroxidase/metabolismo , Estresse Oxidativo/genética , Monoéster Fosfórico Hidrolases/metabolismo , Glândula Tireoide/metabolismo , Linhagem Celular Tumoral , Enzimas Reparadoras do DNA/genética , Glutationa Peroxidase/genética , Humanos , Monoéster Fosfórico Hidrolases/genética , RNA Mensageiro/genética , Glândula Tireoide/citologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Glutationa Peroxidase GPX1RESUMO
Lymph nodes (LNs) play a very important role in the spread of cancer cells. Moreover, it was noticed that the morphology and chemical composition of the LNs change in the course of cancer development. Therefore, finding and monitoring similarities between these characteristics of the LNs and tumor tissues are essential to improve diagnostics and therapy of this dreadful disease. In the present study, we used Raman and Fourier transform infrared (FTIR) spectroscopies to compare the chemical composition of the breast cancer tissues and LNs collected from women without (I group-4 patients) and with (II group-4 patients) recurrence. It was shown that the similarity of the chemical composition of the breast tissues and LNs is typical for the II group of the patients. The average Raman spectrum of the breast cancer tissues from the I group was not characterized by vibrations in the 800-1000 cm-1 region originating from collagen and carbohydrates, which are typical for tumor-affected breast tissues. At the same time, this spectrum contains peaks at 1029 cm-1, corresponding to PO2- from DNA, RNA and phospholipids, and 1520 cm-1, which have been observed in normal breast tissues before. It was shown that Raman bands of the average LN spectrum of the II group associated with proteins and carbohydrates are more intensive than those of the breast tissues spectrum. The intensity of the Raman spectra collected from the samples of the II group is almost three times higher compared to the I group. The vibrations of carbohydrates and amide III are much more intensive in the II group's case. The Raman spectra of the breast cancer tissues and LNs of the II group's samples do not contain bands (e.g., 1520 cm-1) found in the Raman spectra of the normal breast tissues elsewhere. FTIR spectra of the LNs of the I group's women showed a lower level of vibrations corresponding to functional group building nucleic acid, collagen, carbohydrates, and proteins in comparison with the breast cancer tissues. Pearson's correlation test showed positive and more significant interplay between the nature of the breast tissues and LN spectra obtained for the II group of patients than that in the I group's spectra. Moreover, principal component analysis (PCA) showed that it is possible to distinguish Raman and FTIR spectra of the breast cancer tissues and LNs collected from women without recurrence of the disease.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Mama/química , Linfonodos/química , Idoso , Idoso de 80 Anos ou mais , Mama/citologia , Carboidratos/análise , DNA/análise , Feminino , Humanos , Linfonodos/citologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/química , Fosfolipídeos/análise , Análise de Componente Principal , Proteínas/análise , RNA/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodosRESUMO
Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A-U133, set B-HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.
Assuntos
Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Criança , Pré-Escolar , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , TranscriptomaRESUMO
Human papilloma virus (HPV) is highly frequent among patients with anal squamous cell carcinoma, but the viral load (VL) differs between patients. This study aimed to compare the rate of HPV positivity, HPV16VL, p16INK4A and p53 expression between treatment naive and recurrent anal cancer patients. HPV was genotyped via AmpliSens® HPV HCR-genotype-titre-FRT kit. HPV16 VL was determined via quantitative polymerase chain reaction-based in-house test. p16INK4A and p53 expression was tested via immunohistochemistry. The cohort comprised 13 treatment-naive and 17 recurrent anal SCC patients. High-risk HPV was detected in 87% of cases, and HPV16 (73%) was the predominant genotype. The rate of HPV positivity was higher among women and nonsmokers, and majority of HPV-positive cases were also p16INK4A-positive. All p53-negative tumors were HPV16-positive. The most predominant p53 staining pattern in the HPV-positive group was scattered type, whereas it was diffuse type in the HPV-negative group. The HPV16 VL was higher in the treatment-naive group. Further, in the treatment-naive group, cases with scattered staining pattern of p53 had higher HPV16 VL than cases with diffuse staining pattern. The opposite result was noted in the recurrent cancer group. Moreover, p16-positive cases with scattered p53 staining pattern in the treatment naive group had higher HPV16 VL than their counterparts in the recurrent cancer group. In conclusion, the HPV VL, as is the association between VL and p16INK4A /p53, is in an inversed trend in treatment naive and recurrent cancer patients, highlighting the importance of HPV VL measurement in anal SCC.
Assuntos
Neoplasias do Ânus/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Recidiva Local de Neoplasia/epidemiologia , Infecções por Papillomavirus/diagnóstico , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/virologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Polônia/epidemiologia , Prognóstico , Estudos RetrospectivosRESUMO
Currently, breast cancer chemotherapy response can be predicted based on various parameters, with common reporting of tumour grade and Ki67 proliferation index. We analysed their association with pathological complete response (pCR) in a multivariate approach. The study was carried out in a group of 353 patients, treated by preoperative chemotherapy and prospectively observed. In selected patients, parallel to routing core needle biopsy assessment, gene expression profile of tumour was analysed by oligonucleotide microarrays. Tumour parameters associated with pCR in univariate analysis were: tumour grade, nuclear grade, mitotic index, Ki67, oestrogen and progesterone receptor (all p < 0.0001), and triple-negative status (p = 0.0032). The highest increase of pCR chance was observed in patients with high-grade tumours and with Ki67 ≥ 20%. In multivariate analysis, only tumour grade and oestrogen receptor status were predictive for pCR independently of other variables, with high grade increasing the odds of pCR 2.42 fold, and high ER decreasing the chance of pCR 0.41 fold. Tumour grading reflects important biological features of breast cancer and is not inferior to proliferation markers, including Ki67. It should be taken into account in decision-making for preoperative chemotherapy in parallel to breast cancer biologic subtypes, because grade 3 tumours exhibit a higher proportion of pCR.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Gradação de Tumores , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/cirurgia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Resultado do TratamentoRESUMO
Thyroid follicular nodules are quite common in the population, however only a small proportion is malignant. Thyroid cancer differs from adenoma by features of cellular atypia, angioinvasiveness and possibility of metastasis via blood vessels mainly in the lungs and bones. Pathomorphological examination of the postoperative material plays a significant role in the diagnosis of cystic thyroid lesions. De facto, there is no possibility to determine with certainty whether the lesion is benign or malignant before surgery, therefore new methods are being sought to meet clinical needs. The study aimed to investigate if Fourier-transform infrared spectroscopy (FTIR) spectroscopy and Raman spectroscopy combined with multidimensional analysis can be a useful tool in distinguishing between thyroid adenomas and carcinomas. The obtained results indicate quantitative and qualitative alterations within proteins and fats derived from patients' tissues samples. Raman spectroscopy additionally shows significant changes in the amount of tissue collagen due to the pathogenic process. In the spectra of the second FTIR derivative, shifts of vibrations corresponding to the ß-sheet and α-helix structure are observed towards the lower rates of wave numbers in the case of neoplastic tissues. Using the leave-one-out cross-validation, sensitivity and specificity calculated with Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA) clearly shows the possibility to distinguish between pathologically changed and normal thyroid tissue as well as differentiate follicular thyroid adenoma (FTA) from widely invasive follicular thyroid carcinoma (WI-FTC) tissues.
Assuntos
Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patologia , Adenoma/diagnóstico , Adenoma/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Discriminante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodosRESUMO
Thyroid cancer holds the first place of the malignant tumors of the endocrine system. One of the less common thyroid cancers is follicular thyroid carcinoma (FTC), which is very difficult to diagnose because it gives the same image as adenoma, which is benign. Certainty of the diagnosis is gained only when FTC gives metastases. Therefore, it was decided to compare normal and neoplastic (FTC) thyroid tissues with Fourier Transform Infrared (FTIR) spectroscopy. The obtained FTIR spectra and Principal Component Analysis (PCA) allowed us to conclude that there are differences in the FTIR spectrum between normal tissues and those affected by cancer. In addition, the results indicate that there is a decrease in the number of functional groups that build cellular and tissue structures in tumoral tissues. The shifts of wave numbers corresponding to the protein and lipid function group vibrations, as well as the calculated second derivative of the FTIR spectra showed the structural changes in neoplastic tissues. Moreover, the deconvolution of the amide I massif indicates that in cancerous tissues the prevailing secondary structure is ß-sheet structure, while in normal tissues it is α-helix. The obtained results allow us to conclude that infrared spectroscopy, in addition to providing information on the composition of tested samples, can be an excellent diagnostic tool contributing to understanding the FTC substrate.
Assuntos
Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Glândula Tireoide/química , Neoplasias da Glândula Tireoide/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Técnicas Histológicas , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologiaRESUMO
Recent studies involving melanoma cell lines suggest that enhanced expression of epigenetic regulator RNF2 supports proliferation and promotes metastasis. However, it is not clear to what extent those data apply to disease progression and prognosis for melanoma patients. Therefore the aim of the present study was to assess the prognostic power of RNF2 intratumoral expression by melanoma cells. RNF2 was detected immunohistochemically in standard formalin-fixed paraffin-embedded samples of 9 benign nevi, 60 melanomas and 24 nodal metastases. The lowest percentage of RNF2-positive melanocytes found in nevi was comparable to expression levels in normal skin. The RNF2 expression found in melanomas was significantly higher and it was even more enhanced in metastases. The increased occurrence of RNF2 expressing cells was positively correlated with longer patients' overall survival. Moreover, a negative correlation was found between intratumoral RNF2 expression and number of generated metastatic lesions. Our data indicate that development of melanoma is associated with significant changes in RNF2 intratumoral expression and imply that at least for some patients the enhancement of the expression levels of RNF2 in both primary and metastatic lesions may be considered a favorable prognostic factor in melanoma.
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Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines "Diagnostics and Treatment of Thyroid Carcinoma" have been formulated at the "Thyroid Cancer and Other Malignancies of Endocrine Glands" conference held in Wisla in November 2015 [1].
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Sociedades Médicas , Neoplasias da Glândula Tireoide/diagnóstico , Endocrinologia , Feminino , Humanos , Masculino , Oncologia , Patologia , Polônia , Neoplasias da Glândula Tireoide/terapiaRESUMO
Proteomics profiling of tissue specimens representative for major types of thyroid cancers: papillary (classical and follicular variant), follicular, anaplastic and medullary, as well as benign follicular adenoma, was performed using shotgun LC-MS/MS approaches. A combination of Orbitrap and MALDI-TOF approach allowed to identify protein products of 3700 unique genes and revealed large differences between medullary, anaplastic and epithelium-derived differentiated cancers (papillary and follicular). Proteins characteristic for medullary and anaplastic cancers included factors associated with neuroendocrine functions and factors typically associated with advanced malignancies, respectively. Proteomes of different types of epithelium-derived differentiated cancers and follicular adenoma were compared using multi-enzyme LC-MS/MS approach, which revealed products of 4800 unique genes. A comparable overall similarity of follicular cancers to both variants of papillary cancers was found. Moreover, follicular adenoma showed higher overall similarity to follicular cancer than to either variant of papillary cancer. Proteins discriminating differentiated thyroid neoplasms included factors associated with lipid and hormone metabolism, regulation of gene expression and maintenance of DNA structure. Importantly, proteome data matched several features of transcriptome and metabolome profiles of thyroid cancers contributing to systems biology of this malignancy.
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Proteoma/metabolismo , Proteômica/métodos , Neoplasias da Glândula Tireoide/metabolismo , Adenoma/metabolismo , Análise por Conglomerados , Humanos , Proteínas de Neoplasias/metabolismo , Análise de Componente PrincipalRESUMO
BACKGROUND: Histone demethylase JARID1B plays several context dependent roles in epigenetic regulation of cellular differentiation in normal development and is highly expressed in multiple human cancers. The protein is a strong transcriptional repressor capable of downregulating numerous genes. There are three splicing isoforms of JARID1B, however the links between the protein structure and function are not clear. The expression pattern of JARID1B in human melanoma seems to be different from observed in other cancers. Moreover, up to now no data on the impact of JARID1B expression in cutaneous melanoma on the patients' prognosis have been reported. METHODS: We investigated immunohistochemically the association of intratumoral expression of total JARID1B protein and its RBP2-H1 isoform in primary and metastatic melanomas with prognosis for the patients. RESULTS: Expression of both total JARID1B protein and its RBP2-H1 variant was found in all the melanomas investigated. Our results indicate, however, that only high (above 90% of the cells) intratumoral expression of RBP2-H1 can be considered prognostic factor associated with worse overall survival of the patients. CONCLUSIONS: Such results if considered together with data demonstrating a switch to enhanced expression of RBP2-H1 at early stages of malignant transformation of melanocytes are in agreement with hypothetical crucial role of JARID1B in the course of melanoma development and progression and suggest that altered splicing of JARID1B may be important factor increasing melanoma aggressiveness.
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Processamento Alternativo/genética , Biomarcadores Tumorais/genética , Histona Desmetilases com o Domínio Jumonji/genética , Melanoma/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Neoplasias Cutâneas/genética , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Histona Desmetilases com o Domínio Jumonji/metabolismo , Estimativa de Kaplan-Meier , Metástase Linfática , Melanoma/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Proteínas Nucleares/metabolismo , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Zelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.
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Gerenciamento Clínico , Neoplasias Gastrointestinais/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Sociedades Médicas , Endocrinologia , Feminino , Neoplasias Gastrointestinais/terapia , Humanos , Masculino , Oncologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/terapia , PolôniaRESUMO
The role of different types of human papillomavirus (HPV) in the development of oral and oropharyngeal papillomas remains unclear. High-risk HPV (HR-HPV) was shown to be involved in the pathogenesis of significant proportion of squamous cell carcinomas of the oropharynx. In this study, we hypothesized that in some oropharyngeal papillomas, low-risk HPV (LR-HPV) and HR-HPV infection could co-exist, similar to what is observed in genital warts, and thus contribute to the elevated risk of malignancy. To test this hypothesis, we used real-time PCR to assess the presence of HPV DNA of 16 types (2 LR-HPV and 14 HR-HPV), in 75 formalin-fixed and paraffin-embedded histopathological samples of oral and oropharyngeal papillomas and in 57 squamous cell carcinomas from the same regions. We investigated the biological activity of HPV by demonstrating accumulation of P16(INK4A) protein in the viral-infected tissue samples. The presence of the LR-HPV genome from the HPV6 or HPV11 types was confirmed in 42 (56%) papillomas and in no carcinomas. HPV6/HPV11 co-infection was detected in 17 (22.7%) of the papillomas. HR-HPV DNA presence and HR-HPV activity hallmarks were not observed in any of the investigated papillomas. Thus, a causative role for HR-HPV or its contribution to LR/HR-HPV co-infection in the pathogenesis of oral or oropharyngeal papillomas is unlikely. Additionally, HR-HPV and LR-HPV infections seem to be mutually exclusive in papillomas and squamous cell carcinomas of the oral cavity and oropharynx.
Assuntos
Neoplasias Orofaríngeas/virologia , Papiloma/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/metabolismo , Coinfecção , DNA Viral/análise , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Boca/patologia , Boca/virologia , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/epidemiologia , Papiloma/diagnóstico , Papiloma/epidemiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Faringe/patologia , Faringe/virologia , Polônia/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Adulto JovemRESUMO
Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (CPQ, PLVAP, TFF3, ACVRL1, ZFYVE21, FAM189A2, and CLEC3B). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (CPQ, PLVAP, TFF3, ACVRL1). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.