RESUMO
The differential diagnosis of well-differentiated tumors of follicular cell origin remains the most problematic task in thyroid pathology. Specific morphologic criteria (capsular and/or vascular invasion, nuclear characteristics) are crucial in the diagnosis of these neoplasms. However, the assessment of malignant features is inconclusive in some cases. Moreover, oncocytic thyroid tumors remain controversial in a respect to their pathobiology, behavior and management. Therefore, the useful diagnostic/prognostic thyroid markers are awaited. The aim of our study was to evaluate the expression of galectin-3 and thyroid peroxidase (TPO) in benign and malignant thyroid tumors of follicular cell origin. A total of 186 archival thyroid samples including 38 non-oncocytic follicular adenomas, 53 oncocytic (Hürthle cell) adenomas, 6 non-oncocytic follicular carcinomas, 23 oncocytic (Hürthle cell) carcinomas, 43 non-oncocytic papillary carcinomas, and 23 oncocytic papillary carcinomas were analyzed for galectin-3 and TPO expression by immunohistochemistry. Both types of papillary carcinomas showed significant upregulation of galectin-3 in comparison with the other tumor types, likewise, significant differences in galectin-3 expression were discovered between non-oncocytic and oncocytic variants of studied tumors excluding follicular carcinoma. Significant lowering of TPO was revealed in oncocytic adenomas and papillary carcinomas. In conclusion, the combined use of galectin-3 and TPO markers could help to improve the differential diagnosis of thyroid tumors. Differences in the galectin-3 and TPO expression between some oncocytic and non-oncocytic tumors support their separation in the latest WHO classification of thyroid tumors.
Assuntos
Autoantígenos/genética , Galectina 3/genética , Iodeto Peroxidase/genética , Proteínas de Ligação ao Ferro/genética , Neoplasias da Glândula Tireoide/diagnóstico , Biomarcadores Tumorais/genética , Proteínas Sanguíneas , Diagnóstico Diferencial , Galectinas , Humanos , Neoplasias da Glândula Tireoide/classificaçãoRESUMO
BACKGROUND: Central to neoplastic transformation and tumor progression is alteration of the signaling pathways that control cell proliferation and apoptosis. The key mechanisms for this neoplastic process are genetic changes (mutations of cancer-related genes) and recently identified epigenetic changes that involve DNA methylation, chromatin remodeling (which has a profound effect on the control of gene expression), and noncoding, regulatory RNA (notably, microRNA - miRNA). MiRNAs control expression of their target gene post-transcriptionally. These molecular factors have potential as diagnostic, prognostic, and predictive molecular markers. Epithelial tumors of the thyroid gland are a histogenetically, morphologically, and pathobiologically heterogeneous group of neoplasms and require new, molecular approaches in clinical practice. AIM: This review aims to present contemporary scientific knowledge of this molecular (genetic and epigenetic) field of sporadic thyroid tumors of follicular cell origin and their potential clinical implications. The fundamental mutations (BRAFV600E, RET/PTC, RAS, and PAX8-PPARG) in selected tumor types are described comprehensively. Special attention is paid to miRNAs, including their biogenesis, function, and expression profiles in the most common thyroid tumors - follicular adenoma, follicular carcinoma, and papillary carcinoma. CONCLUSION: Thyroid cancer medicine has recently entered a new, molecular era. Comprehensive knowledge of all molecular aspects may improve diagnostics and management of thyroid neoplasms through the introduction of novel, progressive treatment strategies for this cancer. Further research on signaling pathway-related targets, standardization of methods, and evaluation of results are required.Key words: thyroid tumors - cancerogenesis - genetics - epigenetics - microRNA The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 19. 10. 2016Accepted: 2. 11. 2016.
Assuntos
Transformação Celular Neoplásica/genética , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Humanos , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: MicroRNAs (miRNAs), which are endogenously expressed regulatory noncoding RNAs, have an altered expression in tumor tissues. MiRNAs regulate cancer-related processes such as cell growth and tissue differentiation, and therefore, might function as oncogenes or tumor-suppressor genes. The aim of our study was to assess the expression of mir-20a, let-7a, miR-15a and miR-16 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) tissue and to investigate the relation between the expression of miRNAs and the clinicopathological features of PCa. PATIENTS AND METHODS: The study group comprised 138 patients: 85 patients with BPH and 53 patients with PCa. The total RNA was isolated from the tissue specimen core and miRNA expressions were quantified using a real-time RT-PCR method (TaqMan MicroRNA Assays). U6snRNA was used for the normalization of the miRNA expression. RESULTS: miR-20a expression was significantly higher in the group of patients with a Gleason score of 7-10 in comparison with the group of patients with a Gleason score of 0-6 (p=0.0082). We found no statistical differences in the miRNA expressions (mir-20a, let-7a, miR-15a and miR-16) in the PCa tissue samples in comparison with the BPH tissue samples. CONCLUSION: Our result shows that the more dedifferentiated PCa cells have a higher expression of miR-20a and this supports the oncogenic role of miR-20a in PCa carcinogenesis. The evaluation of miRNA expression could yield new information about PCa pathogenesis.
Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: To assess the effect of the cleaning of the posterior capsule using pulses of balanced salt solution (BSS) on the corneal endothelial cells. METHODS: This pilot study involves 43 patients with bilateral cataracts having lens removal using torsional phacoemulsification (Ozil, Infiniti, Alcon) and bimanul irrigation/aspiration (I/A). Posterior capsule of the right eye of each patient was cleaned using pulses of BSS (AquaLase, Infiniti, Alcon). Surgery was performed by one of 2 surgeons (NJ, PR), both eyes of each patient was operated on by the same surgeon. Best corrected visual acuity (BCVA), endotelial cell count and pachymetry were evaluated pre- and postoperatively as well as occurence af peri- and postoperative complications. RESULTS: Preoperative mean pachymetry (P) was 566 +/- 45 microm in the right eye (RE) and 562 +/- 42 microm in the left eye (LE), mean endotelial cell count (ECC) 2541 +/- 317 cells/mm2 (RE) and 2567 +/- 311 cells/mm2 (LE). Three months after surgery P was 557 +/- 43 microm (RE) and 558 +/- 45 microm (LE) and ECC 2368 +/- 416 cells/mm2 (RE) and 2396 +/- 417 cells/mm2 (LE). There was no statistical difference in postoperative changes of both corneal parameters between right and left eyes. Best corrected visual acuity improved in all eyes and no peri-or postoperative complications occured. CONCLUSIONS: Cleaning of the posterior capsule using AquaLase is safe for corneal endothelial cells.
Assuntos
Endotélio Corneano/patologia , Facoemulsificação/instrumentação , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Células Endoteliais/citologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Irrigação Terapêutica/instrumentação , Acuidade VisualRESUMO
Several biological principles such as epigenetic changes, RNA interference, epithelial-mesenchymal transition, and cancer stem cell formation have been recently connected to the pathobiology of tumors. All these phenomena have, along with genetic changes, a significant impact on the neoplastic transformation and/or tumor progression. Authors report a review of the above mentioned "nongenetic" processes and their effect on the neoplastic transformation, and the appearance, behavior, prognosis, and therapy of tumors. Future diagnostic and therapeutic perspectives are also discussed.
Assuntos
Neoplasias/fisiopatologia , Animais , Transformação Celular Neoplásica , Epigênese Genética , Células Epiteliais/fisiologia , Humanos , Mesoderma/fisiologia , Neoplasias/genética , Células-Tronco Neoplásicas/fisiologia , Interferência de RNARESUMO
The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumour progression and the metastatic process by facilitating extracellular matrix degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by matrix metalloproteinase inhibitors have rapidly developed. Low molecular weight tissue inhibitors of matrix metalloproteinase (TIMPs) represent a new therapeutic approach for the treatment of individual types of cancer. This paper aims to briefly summarize current knowledge about the role of MMPs in select non- tumorous lesions, tumor invasion and metastasis. The perspectives in therapeutic intervention in cancer are also mentioned. The role of MMPs in diagnosis and prognosis of colorectal and thyroid cancer is discussed in detail.
Assuntos
Metaloproteinases da Matriz/metabolismo , Neoplasias/enzimologia , Humanos , Inibidores de Metaloproteinases de Matriz , Neoplasias/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/enzimologiaRESUMO
BACKGROUND: With the increased effectiveness of anticancer therapy, much more attention is being paid to the monitoring of the side-effects of chemotherapy, which often constitute a limiting factor in anticancer therapy. In this pilot study, the results of our monitoring of changes in cardio-specific markers and thyroid gland parameters in patients with colorectal carcinoma in the course of adjuvant and palliative chemotherapy are presented. PATIENTS AND METHODS: A total of 42 patients with colorectal carcinoma were monitored (median age 52 years, range 34-82 years); in these patients a post-operative adjuvant or palliative chemotherapy was applied (de Gramont's or FOLFIRI regimen). In all of these patients, the cardio-specific markers brain natriuretic peptide (BNP) and troponin I were assessed, as well as markers of thyroid gland function, TSH and FT4. RESULTS: In the course of chemotherapy, more than half of the patients showed laboratory signs of coronary ischemia; in 6 of these (14%) coronary ischemia was manifested with troponin I levels above 0.3 microg/L. Twenty patients (48%) had laboratory signs of heart failure in the course of adjuvant or palliative chemotherapy. A more frequent incidence of elevated cardio-specific enzymes was observed in continual regimens than in bolus application of fluorouracil. Reduced TSH values were observed in the course of chemotherapy in 9 patients (21%), without changes in FT4 values. An increase in TSH values was observed in 4 patients (10%), again without changes in FT4 values. CONCLUSION: The pilot study demonstrated that in patients undergoing treatment for colorectal carcinoma by adjuvant or palliative chemotherapy on the basis of 5-fluorouracil, it is advisable to check for possible cardiotoxicity and simultaneously to monitor thyroid gland functions. This systematic monitoring may improve the quality of life in cancer patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Coração/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/induzido quimicamente , Peptídeo Natriurético Encefálico/efeitos dos fármacos , Cuidados Paliativos , Projetos Piloto , Tireotropina/efeitos dos fármacos , Tiroxina/efeitos dos fármacos , Troponina I/efeitos dos fármacosRESUMO
INTRODUCTION AND AIM OF STUDY: Czech Republic leads the worldwide league in colorectal cancer's occurrence. Colorectal liver metastases are detected in about a half of patients with colorectal cancer. Liver resection of colorectal metastases is currently the only potentially curative treatment with a chance for a long-term survival rate. Until now there has remained a question of whether adjuvant HAIC can improve the treatment results of radical resection. The aim of our study is to verify predictive efficiency of thymidylátsyntasis (TS), dihydropyrimidindehydrogenasis (DPD) and thymidinfosforylasis (TP) in patients undergoing adjuvant hepatic artery infusion chemotherapy (HAIC) following radical liver resection for colorectal metastases. METHODS: From 1990 to 2005 80 patients underwent 84 liver resections for colorectal metastases. R0 resection was achieved in 60 events. Ten patients who underwent R0 resection both for primary cancer and for colorectal liver metastases and who were given portcatheter for HAIC were included in this study. Adjuvant chemotherapy contained 5-fluorourycil (1200 mg/m2) combined with oxyliplatinum and leukovorin. Whole dose was administered via hepatic artery. The samples were procured both from healthy liver tissue and from metastases for imunohistochemical and molecular biological analysis. RESULTS: The recurrence of disease was verified in 2 of 10 included patients (20%). We detected neither occurrence of death nor serious complication in early postoperative course in none of ten patients. Low expression of TS was found in both events and very high expression of DPD in one event was detected. DISCUSSION: High expression of DPD in one of these patients could contribute to lower outcome of adjuvant chemotherapy. Low expression of TS in both patients responds to the written statement regarding contribution of adjuvant chemotherapy only in patients with high TS level. CONCLUSION: The expression of TS and DPD responds to expected outcome of HAIC. Low number of patient does not permit statistic evaluation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Biomarcadores Tumorais/análise , Quimioterapia Adjuvante , Neoplasias Colorretais/cirurgia , Di-Hidrouracila Desidrogenase (NADP)/análise , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Valor Preditivo dos Testes , Timidina Fosforilase/análise , Timidilato Sintase/análise , Resultado do TratamentoRESUMO
The aim of the study was to determine whether VEGF, TPS, TK or Endostatin determination in tissue cytosol may have some additional value in distinguishing among different types of thyroid lesions. These markers were chosen as representatives of the 2 main pathways (angiogenesis and proliferation) involved in thyroid diseases. VEGF is the most potent angiogenic promoter and Endostatin plays an opposing role. Thymidine kinase (TK) is a marker of DNA synthesis and TPS, cytokeratin 18 fragments, is a marker of the rate of proliferation. We determined qualitatively all four markers in tissue extracts: cytosol from 157 tissue specimens (93 goitre, 12 Hashimoto's thyroiditis, 39 adenomas and 13 carcinomas). In 6 cases we were able to compare both normal and pathological tissue samples from a single patient. Statistically significant differences were found in the measured markers, but outliers were present in all groups. This fact does not permit their use in differential diagnosis. The highest levels of all markers were reached in adenomas, being higher than in carcinomas, probably explained by the higher overall metabolic rate in adenomas.
Assuntos
Citosol/metabolismo , Endostatinas/metabolismo , Timidina Quinase/metabolismo , Doenças da Glândula Tireoide/metabolismo , Glândula Tireoide/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , HumanosRESUMO
BACKGROUND: The differential diagnosis of well-differentiated tumors of follicular cell origin remains a most problematic task in thyroid pathology. Therefore, various diagnostic/prognostic thyroid markers are currently being studied. The aim of our study was to evaluate the proliferative MIB-1 and topoisomerase II-alpha markers in both oncocytic and non-oncocytic epithelial thyroid tumors. MATERIALS AND METHODS: Proliferative activity was analyzed by means of immunohistochemistry in 215 thyroid tumors and the evaluated proliferative indices (PI) were correlated with morphological diagnosis. Comparison of both proliferative markers was made. The results were statistically analyzed using Wilcoxon tests (significance level p<0.05) and the Spearman correlation coefficient. RESULTS: Carcinomas generally showed significantly higher PI than adenomas, irrespective of their oncocytic or non-oncocytic features. Moreover, PI in oncocytic adenomas was significantly higher than in non-oncocytic ones. However, PI in both oncocytic and non-oncocytic carcinomas, including papillary microcarcinomas, were similar. The studied proliferative markers correlated with each other. CONCLUSION: PI can help the differential diagnosis of morphologically difficult cases of thyroid tumors. Oncocytic adenomas have higher malignant potential and should be promptly surgically removed. Both MIB-1 and topoisomerase II-alpha are recommended for the evaluation of thyroid tumor cell proliferation.
Assuntos
Antígenos de Neoplasias , DNA Topoisomerases Tipo II , Proteínas de Ligação a DNA , Antígeno Ki-67 , Neoplasias da Glândula Tireoide/diagnóstico , Divisão Celular , Humanos , Imuno-Histoquímica , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
Human thyroid peroxidase (hTPO) is a membrane protein with a key role in the thyroid hormones synthesis. Loss of hTPO was described in malignant tumours of the thyroid gland. hTPO was tested as a marker of malignancy. Immunohistochemical study of hTPO in 321 thyroid lesions (45 malignant tumours, 72 benign tumours, 199 benign non-tumours lesions, and 5 normal thyroid glands) is presented. The sensitivity of hTPO in predicting malignancy in thyroid is 64%, and the specificity is 87%. Thus, hTPO is of limited value in the diagnosis of thyroid malignancy. The authors discuss the role of hTPO as a marker of differentiation.
Assuntos
Biomarcadores Tumorais/análise , Iodeto Peroxidase/análise , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Idoso , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/químicaRESUMO
AIM: To report a series of six cases of thyroid haemangiosarcoma (HAS) from a non-Alpine region. METHODS AND RESULTS: The patients were four females and two males, aged 54-81 years (average 68 years). The tumours presented as large haemorrhagic masses (diameter 40-70 mm, average 56 mm) with extensive necrosis. Histologically, they were composed of polymorphous epithelioid cells with vesicular nuclei and abundant eosinophilic cytoplasm with occasional intracytoplasmic lumina. Mitotic activity was high. Tumor cells expressed vimentin (6/6), CD31 (6/6), FVIII (5/6), CD34 (2/6), and cytokeratins (5/6). One tumour (1/6) over-expressed p53 protein in more than 20% of cells. Ultrastructurally, Weibel-Palade bodies were present (4/6). Clinical follow-up of four patients (range 3-24 months, median 9 months) showed that two of them have died of the disease 0.5 and 3 months after diagnosis, one died of unrelated causes (with 24 months' uneventful follow-up) and one is alive 21 months after operation with no evidence of disease. CONCLUSIONS: Although thyroid HAS is usually regarded as an extremely aggressive neoplasm with a dismal prognosis similar to anaplastic carcinoma, one of our cases suggests that HAS can behave in a less aggressive way. The morphological, immunohistochemical and ultrastructural findings support the hypothesis that thyroid HAS is a distinct entity, unrelated to other thyroid malignancies.
Assuntos
Células Epitelioides/patologia , Hemangiossarcoma/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Células Epitelioides/química , Evolução Fatal , Feminino , Hemangiossarcoma/química , Hemangiossarcoma/cirurgia , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Mitose , Kit de Reagentes para Diagnóstico , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/cirurgia , Corpos de Weibel-Palade/ultraestruturaRESUMO
Differential diagnosis between malignant and benign thyroid tumors derived from follicular cells can pose certain difficulties in routine surgical pathology. The aim of the study was to evaluate dipeptidyl peptidase IV (DPP IV/CD 26) in differential diagnostics of thyroid lesions. DPP IV/CD 26 was evaluated in thyroid glands of 309 patients (261 females and 48 males, age range of patients 15-80 years). DPP IV/CD 26 was assessed in paraffin-embedded thyroid specimens immunohistochemically using commercially available antibody (Serotec) and biotinylated tyramine amplification kit (DAKO). Well-differentiated carcinoma revealed DPP IV/CD 26 positivity in 33 out of 42 cases (79%). Neither medullary nor insular carcinoma was DPPIV/CD 26 positive (only one case of each tested). DPPIV/CD 26 expression in isolated cells was seen in 18/261 (7%) benign disorders. The sensitivity of the method was 68%, the specificity was 94%, and the diagnostic accuracy was 91%, respectively, using 5% threshold of positive follicular cells. DPP IV/CD 26 can be assessed immunohistochemically using biotinylated tyramine amplification kit. DPP IV/CD 26 could be an adjunct in the thyroid gland differential diagnosis. However, DPP IV/CD 26 positivity is limited to the group of well-differentiated carcinomas, particularly papillary carcinoma. Furthermore, it is of limited value for follicular and oncocytic tumors.
Assuntos
Biomarcadores Tumorais , Dipeptidil Peptidase 4 , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia , TiraminaRESUMO
BACKGROUND: In seeking to improve the differential diagnosis between malignant and benign thyroid tumors of follicular cell origin, we assessed the expression of dipeptidyl peptidase IV (DPP IV) and thyroid peroxidase (TPO). DPP IV is a membrane peptidase expressed in many human tissues, excluding the normal thyroid gland. However, aberrant expression has been described in thyroid carcinomas. TPO is an essential enzyme in the biosynthesis of thyroid hormones with various types of expression in pathological thyroid lesions. MATERIALS AND METHODS: A total of 151 thyroid glands were examined: 24 malignant tumors, 29 benign tumors, 98 benign lesions and 5 normal glands. DPP IV expression was analyzed by a histochemical technique in both frozen sections and imprint/aspirate smears. TPO was assessed immunohistochemically in paraffin-embedded specimens. RESULTS: DPP IV sensitivity in frozen section was 56% and its specificity was 99%, in both cases with a 50% threshold. In cytology, the sensitivity was 68% and the specificity was 98% using the 50% threshold. TPO sensitivity and specificity was 64% and 99%, respectively. The sensitivity and specificity of both markers was 92% and 94%, respectively. CONCLUSION: We recommend adding DPP IV and TPO to the list of diagnostic tumor markers for malignant thyroid tumors of follicular cell origin.
Assuntos
Dipeptidil Peptidase 4/análise , Iodeto Peroxidase/análise , Neoplasias da Glândula Tireoide/diagnóstico , Adenoma/diagnóstico , Adenoma/enzimologia , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/enzimologia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
The authors of this study are concerned with the analysis of optimal criteria for the selection of referential groups in the statistical evaluation of tumor markers for early detection of recurrent disease. Although criteria for the selection of optimal referential groups have already been published on a number of occasions (EGTM recommendation), these criteria are not followed in daily routine, which leads to a false interpretation of results and the impossibility of comparing individual studies. The commonest problem is an incorrect determination of cut-off, caused by not following the recommended specificities at 95%, which results in an incorrect assessment of tumor marker sensitivities. Other faulty interpretations happen in consequence of inaccurate and not clearly defined referential groups, which differ from each other by, for example, stage of the disease, length of the follow-up and so on. Comparing tumor marker results still remains a problem, since they are assessed with diagnostic kits from different manufacturers which may misrepresent the final value of the results, and thus imitate remission or progression of the tumor disease. Similarly, mutual comparison of results from prospective and retrospective studies without standardization of clinical conditions leads to an unreliable interpretation. The authors show, through concrete examples, the possibility of a completely different interpretation of the results in identical referential groups in consequence of their inaccurate characteristics.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/diagnóstico , Neoplasias Colorretais/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Morphological diagnostics of thyroid gland tumours faces certain differential diagnostic problems. Extensive histological examination of the entire tumour is required for the final diagnosis of follicular and oncocytic tumours. Thus, assessment of reliable definitive cytological and/or intraoperative histological diagnosis is not possible. No marker of malignancy has been so far generally accepted in the thyroid tumour diagnosis. The aim of the study was to evaluate membrane protease dipeptidyl peptidase IV (DPP IV) in the differential diagnosis of thyroid tumours. METHODS AND RESULTS: DPP IV was assessed cytochemically in 254 smears, histochemically in 314 cryostat sections, and immunohistochemically in 309 paraffin-embedded sections obtained from the group of 336 patients. There were 283 females and 53 males with the mean age of 48 years (range 15-80 years) in this series. Sensitivity of cytochemical detection was 71%, specificity was 96%, and diagnostic accuracy was 93% using the 50% threshold. Histochemically, sensitivity was 71%, specificity was 93%, and diagnostic accuracy was 90% using the 5% threshold. Using the immunohistochemical assessment, sensitivity was 68%, specificity was 94%, and diagnostic accuracy was 91% using the 5% threshold. CONCLUSIONS: According to our results, DPP IV can be used as a marker of malignancy in well-differentiated carcinomas of follicular cell origin, namely in papillary carcinoma. However, it is less reliable in follicular and oncocytic carcinomas.
Assuntos
Biomarcadores Tumorais/análise , Dipeptidil Peptidase 4/análise , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Histocitoquímica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/químicaRESUMO
To evaluate the significance of Epstein-Barr virus (EBV) infection in tumorogenesis, we examined ten archival samples of acinic cell carcinomas of salivary glands with lymphoid-rich stroma, four archival samples of lymphoepithelioma-like carcinomas (LELC) of the urinary bladder, ten samples of oncocytic papillary carcinoma of the thyroid (Warthin-like tumors) and one sample of lymphoepithelioma-like carcinoma of the cervix, together 25 paraffin-embedded tumor tissues. Polymerase chain reaction (PCR) and in situ hybridization (ISH) assays were used. The EBV genome was detected by PCR using primers targeting the IR region. ISH was performed using EBER oligonucleotide probes. Each examination was repeated two times. Positive PCR result was obtained in 12% of samples only. However, this result was not confirmed by the subsequent second PCR examination. ISH revealed negative signals in all samples. Our results demonstrate the importance of the diagnostic strategy based on combination at least two independent methods. PCR due to its sensitivity may produce false positive results depending on the degree of infiltration the tumor sample by EBV carrying lymphocytes.
Assuntos
DNA Viral/análise , Herpesvirus Humano 4/isolamento & purificação , Neoplasias/virologia , Reações Falso-Positivas , Herpesvirus Humano 4/genética , Humanos , Hibridização In Situ , Linfócitos do Interstício Tumoral/virologia , Inclusão em Parafina , Reação em Cadeia da PolimeraseRESUMO
Fine needle aspiration cytology (FNAC) of the thyroid gland is a well-established method. However, it has inherent limitations, especially in the diagnosis of follicular and oncocytic tumours and in distinguishing between nuclear atypia in colloid goitre with regressive changes and cystic papillary carcinoma. The aim of our study was to evaluate dipeptidyl peptidase IV (DPP IV) as a marker of malignancy in FNAC. We tested 254 thyroid specimens (intraoperative imprint smears) for DPP IV. The sensitivity was 71%, the specificity was 96%, and the diagnostic accuracy was 93%, respectively, with a threshold of 50% of positive cells. To the best of our knowledge it is the largest histologically confirmed study reported in the literature. We suggest the assessment of DPP IV as an adjunct diagnostic marker of malignancy in thyroid specimens suspicious of papillary carcinoma. However, the value of the marker in follicular lesions is very limited.
Assuntos
Dipeptidil Peptidase 4/biossíntese , Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Citodiagnóstico/métodos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Glândula Tireoide/citologia , Glândula Tireoide/patologiaRESUMO
Due to the introduction of fine needle aspiration cytology (FNAC) to the routine clinical preoperative examination surgical pathologists are faced with thyroid gland specimens with FNAC-induced secondary changes. These changes can cause diagnostic difficulties and be a source of incorrect diagnosis. Authors present a review of FNAC-induced changes with differential diagnostic criteria helpful in these pitfalls. FNAC-induced changes can be schematically divided into two major groups--recent ones (intranodal bleeding and/or necrosis) and subacute/late ones (proliferation of granulation tissue with predominance of myofibroblasts or endothelial cells, resorptive pseudoxantomathous granulomas, formation of sarcoid-like granulomas, capsular pseudoinvasion and scarring). Pathologists should be informed about the previously performed FNAC and must be aware of these lesions to prevent their misinterpretation.
Assuntos
Biópsia por Agulha/efeitos adversos , Glândula Tireoide/patologia , Diagnóstico Diferencial , HumanosRESUMO
The use of dipeptidyl aminopeptidase IV (DPP IV) staining by azo-coupling in preoperative and intraoperative diagnostics of thyroid lesions is presented. In a series of 200 histologically confirmed cases examined, the sensitivity and the specificity were 71% and 99%, respectively in 124 smears, and 70% and 94%, respectively in 189 frozen sections. DPP IV expression showed high negative predictive value as well. DPP IV is suggested as an additional tool in the preoperative and intraoperative diagnostics of thyroid lesions.