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1.
Histopathology ; 82(4): 508-520, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36221864

RESUMO

Squamous cell carcinoma (SCC) is the most common malignant tumour of the penis. The 2022 WHO classification reinforces the 2016 classification and subclassifies precursor lesions and tumours into human papillomavirus (HPV)-associated and HPV-independent types. HPV-associated penile intraepithelial neoplasia (PeIN) is a precursor lesion of invasive HPV- associated SCC, whereas differentiated PeIN is a precursor lesion of HPV-independent SCC. Block-type positivity of p16 immunohistochemistry is the most practical daily utilised method to separate HPVassociated from HPVindependent penile SCC. If this is not feasible, the term SCC, not otherwise specified (NOS) is appropriate. Certain histologies that were previously classified as "subtypes" are now grouped, and coalesced as "patterns", under the rubric of usual type SCC and verrucous carcinoma (e.g. usual-type SCC includes pseudohyperplastic and acantholytic/pseudoglandular carcinoma, and carcinoma cuniculatum is included as a pattern of verrucous carcinoma). If there is an additional component of the usual type of invasive SCC (formerly termed hybrid histology), the tumour would be a mixed carcinoma (e.g. carcinoma cuniculatum or verrucous carcinoma with usual invasive SCC); in such cases, reporting of the relative percentages in mixed tumours may be useful. The consistent use of uniform nomenclature and reporting of percentages will inform the refinement of future reporting classification schemes and guidelines/recommendations. The classification of scrotal tumours is provided for the first time in the fifth edition of the WHO Blue book, and it follows the schema of penile cancer classification for both precursor lesions and the common SCC of the scrotum. Basal cell carcinoma of the scrotum may have a variable clinical course and finds a separate mention.


Assuntos
Carcinoma de Células Escamosas , Carcinoma Verrucoso , Neoplasias dos Genitais Masculinos , Infecções por Papillomavirus , Neoplasias Penianas , Neoplasias Cutâneas , Masculino , Humanos , Infecções por Papillomavirus/patologia , Escroto/metabolismo , Escroto/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Penianas/patologia , Papillomavirus Humano , Organização Mundial da Saúde , Papillomaviridae
2.
J Appl Microbiol ; 131(5): 2539-2551, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33788359

RESUMO

AIMS: To determine the occurrence, diversity, antibiotic resistance and biofilm formation of Vibrio parahaemolyticus isolated from marine fishes in Bangladesh. METHODS AND RESULTS: A total of 80 marine fishes were obtained from the local markets and examined for the presence of V. parahaemolyticus. All the isolated V. parahaemolyticus were characterized for the presence of virulence markers, thermostable direct hemolysin (TDH) or thermostable direct hemolysin related hemolysin (TRH). Isolates were serotyped and further characterized by enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) typing to analyse the genetic diversity. Moreover, biofilm formation and antibiotic resistance patterns were also determined. About 63·75% (51/80) of the tested marine fishes were contaminated with V. parahaemolyticus. From the contaminated fishes, 71 representatives V. parahaemolyticus were isolated and none of them harboured tdh and trh virulence genes. Nine different O-groups and seven different K-types were found by serological analysis and the dominant serotype was O5:KUT. In ERIC-PCR analysis, eight clusters (A-H) were found and the most common pattern was A (46·5%). All of the isolates were resistant to ampicillin and 78·9% of isolates were resistant to streptomycin. The highest biofilm formation was found at 37°C compared to 25°C and 4°C. CONCLUSION: Diverse V. parahaemolyticus are present in marine fishes in the local market of Bangladesh with antibiotic-resistant properties and biofilm formation capacity. SIGNIFICANCE AND IMPACT OF THE STUDY: The widespread prevalence of diverse V. parahaemolyticus in marine fishes is an issue of serious concern, and it entails careful monitoring to ascertain the safety of seafood consumers.


Assuntos
Vibrioses , Vibrio parahaemolyticus , Animais , Bangladesh , Peixes , Proteínas Hemolisinas/genética , Alimentos Marinhos , Vibrioses/veterinária , Vibrio parahaemolyticus/genética , Virulência/genética
3.
Pol J Pathol ; 67(2): 97-101, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27543862

RESUMO

Renal anastomosing hemangiomas (RAH) has been recently proposed as a new entity. In this article, we summarize the clinicopathologic features of this tumor. RAH usually develops on a background of end-stage renal disease. Macroscopically, tumors are well-defined and their cut surface shows mahogany brown spongy tissue with epicenter in the renal medulla. Tumors are usually small, but larger lesions are reported. On microscopic examination, the tumor consists of sinusoid-like vascular channels lined by cuboidal endothelial cells with occasional hobnail-like appearance of endothelial cells closely mimicking splenic sinusoids. Eosinophilic hyaline globules may be present in the cytoplasm of neoplastic endothelial cells. Extramedullary hematopoiesis containing erythroid precursor and megakaryocytes may be present in the vascular lumens. Immunohistochemically, endothelial cells are positive for CD31 and CD34, but negative for D2-40, GLUT-1 and HHV8. The surrounding stroma around endothelial cells demonstrates positivity for  smooth muscle action. To date, there are no studies on molecular genetic aspects of RAH. This tumor is indolent based on site and size of the lesion, partial or nephrectomy is sufficient as a therapeutic modality.


Assuntos
Hemangioma/patologia , Neoplasias Renais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Pol J Pathol ; 67(1): 3-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27179267

RESUMO

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Succinato Desidrogenase/genética , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Mutação , Succinato Desidrogenase/deficiência
5.
Histopathology ; 52(6): 674-81, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18393979

RESUMO

AIMS: The distinction between central nervous system (CNS) metastases of clear cell renal cell carcinoma (RCC) and CNS haemangioblastoma still poses a challenge to the pathologist. Since both entities occur in von Hippel-Lindau disease, this aggravates the issue. The antibody renal cell carcinoma marker (RCC-ma) has been suggested to identify primary RCCs specifically, but its value for diagnosing metastases of RCC is controversial. The aim was to assess two distinct clones of the RCC-ma for their potential to: (i) identify primary RCCs and (ii) differentiate between CNS metastases of clear cell RCC and CNS haemangioblastomas. METHODS AND RESULTS: Using tissue microarrays, 77% (n = 363; PN-15) and 66% (n = 355; 66.4C2) of clear cell RCCs, and 93% (PN-15) and 74% (66.4C2) of papillary RCCs (n = 46) were immunopositive for RCC-ma, whereas none of the investigated chromophobe RCCs (n = 22) or any of the oncocytomas (n = 15) showed immunoreactivity. Importantly, 50.9% of CNS metastases of clear cell RCCs (n = 55) exhibited RCC-ma expression, whereas all CNS haemangioblastomas (71) were negative. CONCLUSIONS: Both RCC-ma clones, despite some variation in their sensitivity to detect clear cell and papillary RCCs, are of value in differentiating subtypes of primary RCC and are excellent markers for discriminating clear cell lesions in the brain.


Assuntos
Anticorpos Monoclonais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/secundário , Hemangioblastoma/diagnóstico , Neoplasias Renais/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Carcinoma de Células Renais/patologia , Neoplasias do Sistema Nervoso Central/patologia , Hemangioblastoma/patologia , Humanos , Neprilisina/imunologia , Análise Serial de Tecidos
6.
J Pathol ; 211(1): 18-25, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17072825

RESUMO

Urothelial neoplasms in patients 19 years of age or younger are rare, and the data regarding clinical outcome are conflicting. Molecular data are not available. Urothelial tumours from 14 patients aged 4 to 19 years were analysed, including FGFR3 and TP53 mutation screening, comparative genomic hybridization (CGH), UroVysion FISH analysis, polymerase chain reaction for human papillomavirus (HPV), microsatellite analysis using the NIH consensus panel for detection of microsatellite instability (MSI) and six markers for loss of heterozygosity on chromosome arms 9p, 9q, and 17p and immunohistochemistry for TP53, Ki-67, CK20 and the mismatch repair proteins (MRPs) hMSH2, hMLH1, and hMSH6. Based on the 2004 WHO classification, one urothelial papilloma, seven papillary urothelial neoplasms of low malignant potential (PUNLMPs), five low-grade, and one high-grade papillary urothelial carcinoma were included. No multifocal tumours were found and recurrence was seen in only one patient with a urothelial papilloma. All patients were alive with no evidence of disease at a median follow-up of 3.0 years. We found no mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss, or HPV positivity in any of the patients. Three cases showed chromosome alterations in CGH analyses, urothelial dedifferentiation with CK20 overexpression, or aneuploidy, and one TP53 mutation with TP53 overexpression was found. Urothelial neoplasms in people younger than 20 years are predominantly low grade and are associated with a favourable clinical outcome. Genetic alterations frequently seen in older adults are extremely rare in young patients. Urothelial neoplasms in children and young adults appear to be biologically distinct and lack genetic instability in most cases.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 9 , Papiloma/genética , Neoplasias Urológicas/genética , Urotélio , Adolescente , Adulto , Alphapapillomavirus/genética , Criança , Pré-Escolar , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , DNA Viral/análise , Feminino , Perfilação da Expressão Gênica , Genes p53 , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Perda de Heterozigosidade , Masculino , Instabilidade de Microssatélites , Análise de Sequência com Séries de Oligonucleotídeos , Papiloma/patologia , Reação em Cadeia da Polimerase/métodos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Neoplasias Urológicas/patologia
7.
Histol Histopathol ; 21(3): 325-39, 2006 03.
Artigo em Inglês | MEDLINE | ID: mdl-16372253

RESUMO

Kidney neoplasms are classified by light microscopy using the World Health Organization (WHO) system. The WHO system defines histopathologic tumor subtypes with distinct clinical behavior and underlying genetic mutations. In adults, the common malignant subtypes are variants of renal cell carcinoma (RCC). Histopathologic classification is critical for clinical management of RCC, but is becoming more complex with recognition of novel tumor subtypes, development of procedures yielding small diagnostic biopsies, and emergence of molecular therapies directed at tumor gene activity. Therefore, classification systems based on gene expression are likely to become essential for diagnosis, prognosis and treatment of kidney tumors. Recent DNA microarray studies have shown that clinically relevant renal tumor subtypes are characterized by distinct gene expression profiles, which are useful for discovery of novel diagnostic and prognostic biomarkers. In this review, we summarize the WHO classification system for renal tumors, general applications of microarray technology in cancer research, and specific microarray studies that have advanced knowledge of renal tumor diagnosis, prognosis, therapy and pathobiology.


Assuntos
Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/genética , DNA de Neoplasias/análise , Neoplasias Renais/classificação , Neoplasias Renais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Histocitoquímica/métodos , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Organização Mundial da Saúde
8.
J Urol ; 173(5): 1492-5, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15821466

RESUMO

PURPOSE: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. MATERIALS AND METHODS: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. RESULTS: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p = 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p = 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p = 0.001 and 5.49, p = 0.001) and for the CRCC subtype (RR 5.50, p = 0.001 and 5.18, p = 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p = 0.001). All statistical analyses were adjusted for age and sex. CONCLUSIONS: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Urotélio/patologia
9.
Histopathology ; 45(3): 218-25, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15330799

RESUMO

AIM: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. METHODS AND RESULTS: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). CONCLUSIONS: We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Próstata/patologia , Racemases e Epimerases/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Racemases e Epimerases/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Histopathology ; 42(2): 167-72, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12558749

RESUMO

AIMS: There is no well-established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34betaE12 in differentiating high-grade invasive urothelial carcinoma from prostate cancer. METHODS AND RESULTS: Formalin-fixed paraffin-embedded sections from 28 cases of high-grade invasive urothelial carcinoma (20 not otherwise specified (UC-NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34betaE12 after microwave pretreatment or protease 24 predigestion. All cases of UC-NOS expressed HMWCK on 34betaE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34betaE12, 85A12 was insensitive with 15% of UC-NOS cases totally CEA-negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti-CEA and 34betaE12 on microwaved sections, but all the cases were HMWCK-negative using 34betaE12 on sections pretreated by enzyme digestion. CONCLUSIONS: HMWCK antibody clone 34betaE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high-grade invasive urothelial carcinoma.


Assuntos
Adenocarcinoma/metabolismo , Carcinoma de Células de Transição/metabolismo , Queratinas/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adenocarcinoma/química , Adenocarcinoma/patologia , Anticorpos Monoclonais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , Carcinoma de Células de Transição/química , Carcinoma de Células de Transição/secundário , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/métodos , Queratinas/análise , Queratinas/imunologia , Masculino , Neoplasias da Próstata/química , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/patologia
12.
Am J Surg Pathol ; 26(12): 1588-96, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12459625

RESUMO

P504S is a recently described, prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. A recent study has shown that immunohistochemical detection of P504S gene product is a sensitive and specific marker of prostatic carcinoma in formalin-fixed, paraffin-embedded tissues. We performed a detailed analysis of P504S protein expression in a large series of prostate and bladder specimens with special emphasis on staining in specific morphologic patterns of prostatic adenocarcinoma, posthormonal and radiation therapy cases, and invasive urothelial carcinoma. A total of 366 prostate needle core biopsies from 124 patients with prostate cancer, 10 biopsies from 2 patients without prostate cancer, 28 prostatectomy specimens (16 with specific morphologic patterns, 7 posthormonal therapy and 5 postradiation therapy specimens), 5 bladder specimens with invasive urothelial carcinoma, and a single transurethral resection specimen from a patient with hormonally treated prostate cancer and invasive urothelial carcinoma were stained with P504S monoclonal antibody at a 1:250 dilution using standard heat-induced epitope retrieval and avidin-biotin technique. Extent (0, no staining; 1+, 1-10% staining; 2+, 11-50% staining; 3+, > or =51% staining) and location (luminal, subluminal, and diffuse cytoplasmic) of immunoreactivity in carcinoma and benign tissues were recorded. A total of 153 of 186 biopsies (82%) with prostatic adenocarcinoma stained for P504S. Pseudohyperplastic, atrophic, ductal, and mucinous prostatic carcinomas stained similarly, as did cases treated with hormone or radiotherapy. In 81 of 377 (21%) foci of benign prostatic tissue there was staining that was almost always focal, faint, and noncircumferential. Seminal vesicles did not stain for P504S. Five of six (83%) specimens with invasive urothelial carcinoma had 2+ staining and one case had focal staining. We conclude that immunohistochemistry for P504S has potential utility in the diagnosis of prostate cancer, including those treated by hormones and radiation. Circumferential luminal to subluminal and diffuse cytoplasmic staining is the most specific staining pattern for prostatic carcinoma and is almost never associated with benign prostatic tissue. However, a negative P504S immunostain does not automatically rule out prostate cancer, as 18% of cases were negative. Additionally, occasional benign glands, high-grade prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, and urothelial carcinoma may express P504S. Therefore, we think that P504S is best used only in conjunction with strict light microscopic correlation and preferably with high molecular weight cytokeratin immunostaining.


Assuntos
Biomarcadores Tumorais/análise , Biópsia por Agulha , Carcinoma/enzimologia , Neoplasias da Próstata/enzimologia , Racemases e Epimerases/análise , Anticorpos Monoclonais , Biomarcadores Tumorais/imunologia , Biópsia por Agulha/instrumentação , Carcinoma/cirurgia , Carcinoma de Células de Transição/enzimologia , Corantes , Cistectomia , Amarelo de Eosina-(YS) , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Hematoxilina , Humanos , Imuno-Histoquímica , Masculino , Estudos Prospectivos , Próstata/enzimologia , Prostatectomia , Neoplasias da Próstata/cirurgia , Racemases e Epimerases/genética , Racemases e Epimerases/imunologia , Coloração e Rotulagem
13.
Gene ; 279(1): 17-31, 2001 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-11722842

RESUMO

Ectopical expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the development and malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. We cloned and characterized the human MUC18 (huMUC18) cDNA gene from three human prostate cancer cell lines and three human melanoma cell lines. The cDNA sequences from the six human cancer cell lines were identical except differences in one to five nucleotides. The deduced amino acid sequences of the longest ORF were 646 amino acids that were identical in these cDNAs except for one to three amino acid residues. The amino acid sequences of all our huMUC18 cDNA genes are similar to that cloned by other group (GenBank access #M28882) except differences in the same seven amino acids. We conclude that huMUC18 cDNA gene reported here represents the gene product from a major allele. The MUC18 mRNA and protein was expressed in three metastatic prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one non-metastatic prostate cancer cell line (LNCaP.FGC). The expression of huMUC18 in these four cell lines is positively related to their extent of in vitro motility and invasiveness and in vivo metastasis in nude mice. HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from cultured primary normal prostatic epithelial cells and the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas, and in cells of a perineural invasion, a lymph node, and a lung metastases compared to that in normal or benign hyperplastic epithelium (BPH). We therefore conclude that MUC18 expression is increased during prostate cancer initiation (high grade PIN) and progression to carcinoma, and in metastatic cell lines and metastatic carcinoma. Increased expression of MUC18 is implicated to play an important role in developing and malignant progression of human prostate cancer. Furthermore, the lacking of predominant cytoplasmic membrane expression of MUC18 appeared to correlate with malignant progression of prostate cancer.


Assuntos
Antígenos CD , Antígenos de Superfície/genética , DNA Complementar/genética , Glicoproteínas de Membrana , Moléculas de Adesão de Célula Nervosa , Neoplasias da Próstata/genética , Sequência de Aminoácidos , Antígenos de Superfície/metabolismo , Sequência de Bases , Antígeno CD146 , Membrana Celular/metabolismo , Movimento Celular , Citoplasma/metabolismo , DNA Complementar/química , DNA Complementar/isolamento & purificação , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Melanoma/genética , Melanoma/patologia , Dados de Sequência Molecular , Invasividade Neoplásica , Próstata/química , Próstata/citologia , Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Células Tumorais Cultivadas
14.
Am J Surg Pathol ; 25(12): 1515-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11717541

RESUMO

Signet-ring cell carcinoma (SRCC) of lung is a rare variant of pulmonary adenocarcinoma. In view of this rarity, the question of whether an SRCC is primary pulmonary or metastatic arises frequently because the majority of SRCCs seen in lung are metastatic tumors having arisen in stomach, colon, or breast. On routine histologic examination it is difficult to distinguish between pulmonary SRCC from SRCC metastasizing from other organs. Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is almost exclusively expressed in thyroid and pulmonary epithelial cells. TTF-1 expression has been demonstrated in various neoplasms of lung; however, the expression of TTF-1 in SRCCs has not been investigated so far. In the present study, using an immunoperoxidase staining procedure on paraffin sections, we investigated the expression of TTF-1, cytokeratin 7, cytokeratin 20, and villin (a specific marker expressed in tumors of the digestive tract, renal proximal tubules, and hepatic bile ducts) in 32 SRCCs from various organs (17 lung, 5 breast, 5 stomach, and 5 colon). Fourteen (82.4%) of 17 pulmonary SRCCs exhibited TTF-1 positivity, whereas none of the SRCCs of other organs were positive for TTF-1. A cytokeratin profile (CK7+/CK20-) was identified in 94.1% of pulmonary SRCC, and although it differed from the profile exhibited in colonic SRCCs (CK7-/CK20+), a similar profile was seen in breast SRCCs and some SRCCs arising in the stomach. Villin was identified in 29.4% of pulmonary SRCCs and 20% (one case) arising in the breast. Although the pattern of villin immunostaining exhibited by nondigestive tract SRCCs (cytoplasmic) differed from those of digestive tract SRCCs (membranous), distinguishing between the two groups based on their pattern of immunostaining alone would be difficult. The results of this study indicate that TTF-1 is expressed in a high percentage of pulmonary SRCCs and is very specific and that TTF-1 would be extremely valuable in distinguishing pulmonary SRCCs from those arising in other organs.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Neoplasias Pulmonares/diagnóstico , Biomarcadores Tumorais/análise , Carcinoma de Células em Anel de Sinete/química , Carcinoma de Células em Anel de Sinete/secundário , Proteínas de Transporte/análise , Diagnóstico Diferencial , Humanos , Técnicas Imunoenzimáticas , Proteínas de Filamentos Intermediários/análise , Queratina-20 , Queratina-7 , Queratinas/análise , Neoplasias Pulmonares/química , Proteínas dos Microfilamentos/análise , Metástase Neoplásica/diagnóstico , Proteínas Nucleares/análise , Sensibilidade e Especificidade , Fator Nuclear 1 de Tireoide , Fatores de Transcrição/análise
15.
Prostate ; 48(4): 305-15, 2001 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-11536311

RESUMO

BACKGROUND: Over expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. METHODS: RT-PCR and Western blot analyses were used to analyze the expression of MUC18 mRNA and protein in four human prostate cancer cell lines, cultured primary normal prostate epithelial cells, normal prostate and malignant prostate tissues. Immunohistochemistry was used to determine the expression of MUC18 antigen in prostatic tissues at different stages of malignancy. RESULTS: Human MUC18 mRNA and protein was expressed in three different prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one prostate cancer cell line (LNCaP.FGC). HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from either cultured primary normal prostatic epithelial cells or the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas and in cells of a lymph node metastasis compared to that in normal or benign hyperplastic epithelium (BPH). CONCLUSIONS: We therefore conclude that MUC18 is expressed at higher levels in pre-malignant and malignant prostatic epithelium, including metastasis. We suggest that over-expression of MUC18 may be a new marker of human prostate cancer and also implicates its possible role in development and progression of prostate cancer.


Assuntos
Antígenos CD , Antígenos de Superfície/biossíntese , Moléculas de Adesão Celular/biossíntese , Glicoproteínas de Membrana , Moléculas de Adesão de Célula Nervosa , Neoplasias da Próstata/metabolismo , Antígenos de Superfície/genética , Northern Blotting , Western Blotting , Antígeno CD146 , Moléculas de Adesão Celular/genética , DNA Complementar/genética , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Lesões Pré-Cancerosas/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
16.
Am J Pathol ; 159(2): 483-91, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11485907

RESUMO

Angiomyolipomas are benign tumors of the kidney derived from putative perivascular epithelioid cells, that may undergo differentiation into cells with features of melanocytes, smooth muscle, and fat. To gain further insight into angiomyolipomas, we have generated the first human angiomyolipoma cell line by sequential introduction of SV40 large T antigen and human telomerase into human angiomyolipoma cells. These cells show phenotypic characteristics of angiomyolipomas, namely differentiation markers of smooth muscle (smooth muscle actin), adipose tissue (peroxisome proliferator-activator receptor gamma, PPARgamma), and melanocytes (microophthalmia, MITF), thus demonstrating that a single cell type can exhibit all of these phenotypes. These cells should serve as a valuable tool to elucidate signal transduction pathways underlying renal angiomyolipomas.


Assuntos
Angiomiolipoma/patologia , Neoplasias Renais/patologia , Telomerase/metabolismo , Actinas/análise , Tecido Adiposo/citologia , Tecido Adiposo/patologia , Angiomiolipoma/genética , Angiomiolipoma/ultraestrutura , Antígenos Transformantes de Poliomavirus/genética , Técnicas de Cultura de Células/métodos , Humanos , Imuno-Histoquímica , Neoplasias Renais/genética , Neoplasias Renais/ultraestrutura , Melanócitos/citologia , Melanócitos/patologia , Proteínas Quinases Ativadas por Mitógeno/análise , Músculo Liso/citologia , Músculo Liso/patologia , Fenótipo , Fosforilação , Proteínas/análise , Proteínas/genética , Receptores Citoplasmáticos e Nucleares/análise , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Repressoras/análise , Proteínas Repressoras/genética , Vírus 40 dos Símios/genética , Telomerase/análise , Fatores de Transcrição/análise , Fatores de Transcrição/metabolismo , Transfecção , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor
17.
Am J Surg Pathol ; 25(8): 1074-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11474293

RESUMO

Distinction of urothelial carcinoma in situ (CIS) from reactive atypia on the basis of morphology alone may be difficult in some cases. Because this distinction is therapeutically and prognostically critical, we attempted to determine if an immunohistochemical panel would help in this differential diagnosis. The immunoprofile of 21 cases of CIS and 25 non-neoplastic urothelia (15 urothelial biopsies with reactive atypia from patients without a history of bladder cancer and 10 normal ureter sections from nephrectomies performed for renal cell carcinoma) was determined using antibodies against cytokeratin 20 (CK20), p53, and CD44 (standard isoform). In the normal urothelium CK20 showed patchy cytoplasmic immunoreactivity in only the superficial umbrella cell layer and CD44 stained only the basal cells. Nuclear immunoreactivity to p53 varied from negative to weak and patchy. Reactive urothelium also showed CK20 immunoreactivity in only the umbrella cell layer in all 15 cases, and p53 nuclear staining was predominantly negative with occasional weak positivity in the basal and parabasal intermediate cells. CD44 was overexpressed in the entire reactive urothelium in 9 cases (60%) or focally positive in intermediate cells in 6 cases (40%). In contrast, CIS showed intense CK20 and p53 positivity (81% and 57%, respectively) in the majority (>50%) of malignant cells. CD44 staining revealed residual basal cells with membranous reactivity in 44% of the cases of CIS; however, the neoplastic cells were immunonegative in all cases. At least one positive immunomarker (CK20 or p53) was abnormally expressed in all cases of CIS. Abnormal expression of CK20 (increased), p53 (increased), and CD44 (decreased) in urothelial CIS, and increased expression of CD44 in reactive atypia allows more confident distinction of urothelial CIS from non-neoplastic urothelial atypias. From a differential diagnosis perspective, use of a panel of all three antibodies with morphologic correlation would be essential.


Assuntos
Carcinoma in Situ/patologia , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Biomarcadores Tumorais/análise , Carcinoma in Situ/química , Carcinoma de Células de Transição/química , Diagnóstico Diferencial , Humanos , Receptores de Hialuronatos/análise , Técnicas Imunoenzimáticas , Proteínas de Filamentos Intermediários/análise , Queratina-20 , Proteína Supressora de Tumor p53/análise , Neoplasias da Bexiga Urinária/química , Urotélio/anatomia & histologia , Urotélio/química
18.
APMIS ; 109(4): 295-8, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11469501

RESUMO

Paneth cell-like metaplasia has been reported in the epithelium of the epididymis and prostatic adenocarcinomas. We studied the expression of group II phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2 gave negative results in all six cases but positive reaction for lysozyme. The results show that the cells of the Paneth cell-like metaplasia are not true Paneth cells.


Assuntos
Epididimo/enzimologia , Celulas de Paneth/enzimologia , Fosfolipases A/metabolismo , Biomarcadores , Grânulos Citoplasmáticos/enzimologia , Grânulos Citoplasmáticos/patologia , Epididimo/patologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Metaplasia , Muramidase/metabolismo , Celulas de Paneth/patologia , Fosfolipases A/classificação , Fosfolipases A/genética , Fosfolipases A2 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
19.
Am J Pathol ; 158(5): 1639-51, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11337362

RESUMO

The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.


Assuntos
Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica , Neoplasias Renais/genética , Adulto , Idoso , Antígenos de Diferenciação/análise , Antígenos de Diferenciação de Linfócitos B/análise , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Feminino , Galectina 3 , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/análise , Humanos , Imuno-Histoquímica , Rim/química , Rim/patologia , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Parvalbuminas/análise , Vimentina/análise
20.
Arch Pathol Lab Med ; 125(6): 751-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11371226

RESUMO

BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.


Assuntos
Angiomiolipoma/imunologia , Angiomiolipoma/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Actinas/metabolismo , Adipócitos/patologia , Adulto , Idoso , Angiomiolipoma/metabolismo , Antígenos CD/metabolismo , Antígenos de Neoplasias , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Humanos , Imunofenotipagem , Neoplasias Renais/metabolismo , Masculino , Antígenos Específicos de Melanoma , Melanossomas/patologia , Proteínas dos Microfilamentos , Microscopia Eletrônica , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/metabolismo , Músculo Liso/patologia , Proteínas de Neoplasias/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Tetraspanina 30 , Calponinas
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