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Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts, fibromas, fibroadenomas, lipomas and hamartomas. Adenoma was the tentative diagnosis is this case history, but the histology showed a benign leiomyoma.
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Leiomioma , Neoplasias de la Vulva , Humanos , Femenino , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/diagnóstico , Leiomioma/patología , Leiomioma/diagnóstico por imagen , Leiomioma/diagnóstico , Adulto , Persona de Mediana Edad , Diagnóstico DiferencialRESUMEN
Melanized focal changes (MFCs) in the fillet of farmed Atlantic salmon is a major quality concern. The changes are thought to initially appear as acute red focal changes (RFCs) that progress into chronic MFCs. Recent findings have indicated that hypoxia may be important in their development, possibly leading to necrosis affecting not only myocytes but also adipocytes. Thus, the aim of this study was to investigate possible hypoxic conditions in RFCs and the subsequent inflammatory responses and lesions in the adipose tissue in RFCs and MFCs. A collection of RFCs, MFCs and control muscle samples from several groups of farmed salmon was studied. Using immunohistochemistry, we found induction of the hypoxia-inducible factor 1 pathway in RFCs. Histological investigations of RFCs and MFCs revealed different stages of fat necrosis, including necrotic adipocytes, a myospherulosis-like reaction and the formation of pseudocystic spaces. Accumulations of foamy macrophages were detected in MFCs, indicating degradation and phagocytosis of lipids. Using in situ hybridization, we showed the presence of tyrosinase- and tyrosinase-related protein-1-expressing amelanotic cells in RFCs, which in turn became melanized in MFCs. In conclusion, we propose a sequence of events leading to the formation of MFCs, highlighting the pivotal role of adiposity, hypoxia and fat necrosis.
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BACKGROUND: Endoscopic screening with polypectomy reduces the incidence of colorectal cancer (CRC). Incomplete polyp removal may attenuate the effect of screening. This randomized trial compared cold snare polypectomy (CSP) with hot snare polypectomy (HSP) in terms of complete polyp resection. METHODS: We included patients ≥â40 years of age at eight hospitals in four countries who had at least one non-pedunculated polyp of 4-9âmm detected at colonoscopy. Patients were randomized 1:1 to CSP or HSP. Biopsies from the resection margins were obtained systematically after polypectomy in both groups. We hypothesized that CSP would be non-inferior to HSP, with a non-inferiority margin of 5â%. Logistic regression models were fitted to identify the factors explaining incomplete resection. RESULTS: 425 patients, with 601 polyps, randomized to either CSP or HSP were included in the analysis. Of 318 polyps removed by CSP and 283 polyps removed by HSP, 34 (10.7â%) and 21 (7.4â%) were incompletely resected, respectively, with an adjusted risk difference of 3.2â% (95â%CI -1.4â% to 7.8â%). There was no difference between the groups in terms of post-polypectomy bleeding, perforation, or abdominal pain. Independent risk factors for incomplete removal were serrated histology (odds ratio [OR] 3.96; 95â%CI 1.63 to 9.66) and hyperplastic histology (OR 2.52; 95â%CI 1.30 to 4.86) in adjusted analyses. CONCLUSION: In this randomized trial, non-inferiority for CSP could not be demonstrated. Polyps with serrated histology are more prone to incomplete resection compared with adenomas. CSP can be used safely for small polyps in routine colonoscopy practice.
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Adenoma , Pólipos del Colon , Adenoma/patología , Adenoma/cirugía , Biopsia , Pólipos del Colon/patología , Pólipos del Colon/cirugía , Colonoscopía/efectos adversos , Humanos , MicrocirugiaRESUMEN
BACKGROUND: Endoscopic screening with polypectomy has been shown to reduce colorectal cancer incidence in randomized trials. Incomplete polyp removal and subsequent development of post-colonoscopy cancers may attenuate the effect of screening. This study aimed to quantify the extent of incomplete polyp removal. METHODS: We included patients aged 50-75 years with nonpedunculated polypsâ≥â5âmm removed during colonoscopy at four hospitals in Norway. To evaluate completeness of polyp removal, biopsies from the resection margins were obtained after polypectomy. Logistic regression models were fitted to identify factors explaining incomplete resection. RESULTS: 246 patients with 339 polyps underwent polypectomy between January 2015 and June 2017.âA total of 12 polyps were excluded due to biopsy electrocautery damage, and 327 polyps in 246 patients (mean age 67 years [range 42-83]; 52â% male) were included in the analysis. Overall, 54 polyps (15.9â%) in 54 patients were incompletely resected. Histological diagnosis of the polyp (sessile serrated lesions vs. adenoma, odds ratio [OR] 10.9, 95â% confidence interval [CI] 3.9-30.1) and polyp location (proximal vs. distal colon, OR 2.8, 95â%CI 1.0-7.7) were independent risk factors for incomplete removal of polyps 5-19âmm. Board-certified endoscopists were not associated with lower rates of incomplete resection compared with trainees (14.0â% vs. 14.2â%), OR 1.0 (95â%CI 0.5-2.1). CONCLUSION: Incomplete polyp resection was frequent after polypectomy in routine clinical practice. Serrated histology and proximal location were independent risk factors for incomplete resection. The performance of board-certified gastroenterologists was not superior to that of trainees.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pólipos del Colon/cirugía , Colonoscopía , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Estudios ProspectivosRESUMEN
INTRODUCTION: Because individuals with serrated polyps and adenomas are at increased risk of developing new polyps and colorectal cancer (CRC), surveillance after resection is justified. After adenoma resection, most international guidelines are consistent, but recommendations for surveillance after serrated polyp resection vary. The United States Multi-Society Taskforce on CRC (US-MSTF) base surveillance intervals on serrated polyp subtype (traditional serrated adenoma, sessile serrated polyp, hyperplastic polyps), while the European Society of Gastrointestinal Endoscopy (ESGE) guidelines do not take serrated polyp subtype into account. We evaluated the implications of this difference in a primary colonoscopy screening cohort. METHODS: We included participants from a large colonoscopy screening trial. In a post-hoc simulation, assuming full protocol adherence, we determined the surveillance interval for each subject based on their polyp burden, using the most recent US-MSTF and ESGE guidelines. RESULTS: We included 5323 participants, of whom 1228 had one or more serrated polyps. In 5201 of all participants (98â%; Cohen's kappa 0.90) and in 1106 of those with serrated polyps (90â%; Cohen's kappa 0.80), both guidelines recommended identical surveillance intervals. Recommendations for a 3-year surveillance interval were identical between the two guidelines. All 122 subjects with discordant recommendations would receive a follow-up colonoscopy after 10 years using ESGE guidance and after 5 years using US-MSTF guidance. CONCLUSION: Despite the different criteria used to determine surveillance after serrated polyp resection, most individuals are recommended identical colonoscopy surveillance intervals whether following the ESGE or US-MSTF guidelines. This suggests that surveillance recommendations do not need to consider the serrated polyp subtype.
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Adenoma/diagnóstico por imagen , Pólipos del Colon/diagnóstico por imagen , Colonoscopía , Neoplasias Colorrectales/diagnóstico por imagen , Vigilancia de la Población , Guías de Práctica Clínica como Asunto , Adenoma/epidemiología , Adenoma/patología , Pólipos del Colon/epidemiología , Pólipos del Colon/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
AIMS: In the near future, an immunoscore based on the quantification of lymphocytic populations can be expected as a fundamental supplement of colorectal cancer (CRC) classification. This study explored whether latent viral infection has an influence on prognostically relevant host immunity in CRC. METHODS AND RESULTS: CD8+ lymphocytic infiltration in three tumour compartments of 121 CRC was compared with clinical data and occurrence of latent infection with herpes simplex virus (HSV1, HSV2), cytomegalovirus (CMV), human papillomavirus (HPV16 and HPV18) in the tumour tissue, which was determined by polymerase chain reaction (PCR). Intraepithelial CD8+ lymphocytic infiltration (IECD8+ ) showed a trend towards correlation with clinical stage (P = 0.073), significant differences between CRC with and without metastases (P = 0.001) and a significant correlation with overall survival (OS, P = 0.001). Each of these three clinical parameters showed a significant link to IECD8+ in the virus DNA-negative (P-values: 0.001-0.036), but no significant differences in the virus DNA-positive subgroup, which is consistent with a moderating effect of virus DNA on these associations. A significant correlation of CD8+ infiltration in the invasive margin (IMCD8+ ) with OS (P = 0.016) was also moderated by virus DNA. CONCLUSION: Our data suggest a possible influence of latent viral infection on the association between clinical outcome and CD8+ lymphocytic infiltration in CRC tissue. After confirmation of these results by large cohort studies, a potential interaction between microbial pathogens and host immunity in CRC and its impact on prognostic immunoscores and/or new therapeutic strategies should be investigated further.
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Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/virología , Linfocitos Infiltrantes de Tumor/inmunología , Infecciones Tumorales por Virus/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD8-positivos/inmunología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/inmunología , Femenino , Herpes Simple/complicaciones , Herpes Simple/inmunología , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/inmunología , Infecciones Tumorales por Virus/inmunología , Latencia del Virus/inmunologíaRESUMEN
This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) ( p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) ( p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases ( p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , ADN Mitocondrial/genética , Inestabilidad de Microsatélites , Adulto , Anciano , Anciano de 80 o más Años , Fosfatidilinositol 3-Quinasa Clase I , Femenino , GTP Fosfohidrolasas/genética , Humanos , Metástasis Linfática/genética , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Tasa de Mutación , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
AIMS: Failure and side effects of combined cytotoxic therapy are challenges in the treatment of metastatic colorectal cancer (CRC). DPYD gene variations can potentially predict toxicity to 5-fluorouracil (FU)-based therapy and KRAS-, NRAS-, BRAF-, PIK3CA-wild type status is a known prerequisite for epidermal growth factor receptor (EGFR) inhibitor therapy. This study was performed to search for a possible link between these therapeutic markers. METHODS: The DPYD gene variations c.496A>G, c.1679T>G, c.2846A>T and KRAS/NRAS/BRAF/PIK3CA mutational status were determined in non-neoplastic, primary CRC and metastatic CRC tissue from 115 patients. RESULTS: The polymorphism c.496A>G was the DPYD gene variant with the highest detection rate (12.9%), occurred predominantly in females (86.7%, p=0.0044) and was exclusively seen in KRAS wild type primary CRC (15/65 (23.1%) vs 0/51 (0%) in KRAS-mutated primary CRC, respectively, p=0.0001). CONCLUSIONS: This genetic profile could define a patient group requiring alternative combined therapeutic approaches. Global testing of large patient cohorts is necessary to prove this concept.
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Neoplasias Colorrectales/genética , Dihidrouracilo Deshidrogenasa (NADP)/genética , Mutación , Polimorfismo Genético , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/metabolismo , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Farmacogenética , Fenotipo , Medicina de Precisión , Valor Predictivo de las Pruebas , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Neuroendocrine differentiation in sporadic colorectal cancer has been recognized since decades, but its clinical impact is still controversially discussed. Detailed parameter analyses hint at the possibility that probably not neuroendocrine differentiation itself, but its association with poor grade of tumor differentiation, lymph node metastases, distant metastases and other unfavorable features contribute to worse clinical outcome. However, other studies deny a relationship between neuroendocrine differentiation and prognosis of colorectal cancer. This review elucidates, whether new insights into the origin of neuroendocrine differentiation in the intestinal epithelium, its regulation by mTOR pathway components and its possible link to the intestinal stem cell compartment could determine a role of neuroendocrine cells as prognostic marker and putative therapeutic target in sporadic colorectal cancer.
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Diferenciación Celular , Neoplasias Colorrectales/patología , Células Enteroendocrinas/patología , Mucosa Intestinal/patología , Células Madre Neoplásicas/patología , Tumores Neuroendocrinos/patología , Animales , Biomarcadores/metabolismo , Linaje de la Célula , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/terapia , Células Enteroendocrinas/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Células Madre Neoplásicas/metabolismo , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/terapia , Fenotipo , Pronóstico , Transducción de SeñalRESUMEN
BACKGROUND AND STUDY AIMS: Compared with air insufflation, water exchange and carbon dioxide (CO2) insufflation have been shown to reduce colonoscopy discomfort; however, head-to-head studies of the two methods are lacking. We aimed to compare water exchange and CO2 insufflation directly with regard to pain during primary unsedated colonoscopy. METHODS: Patients willing to undergo unsedated colonoscopy at three centers in Norway and Poland were randomized 1:1 to water exchange or CO2 insufflation during colonoscope insertion. Patients were blinded to group allocation. The primary end point was the proportion of patients reporting moderate or severe procedural pain on a 4-point verbal rating scale (VRS-4) at discharge. Secondary outcomes included the proportion of patients reporting no pain on the VRS-4. RESULTS: A total of 473 patients were randomized. A discharge pain questionnaire was completed by 226 of 234 patients (97â%) in the water exchange group versus 226 of 239 patients (95â%) in the CO2 group (Pâ=â0.37). Moderate or severe pain was reported by 47 of 226 patients (21â%) in the water exchange group versus 60 of 226 patients (27â%) in the CO2 group (Pâ=â0.15). No pain was reported by 100 of 226 patients (44â%) and 69 of 226 patients (31â%) in the water exchange and CO2 groups, respectively (Pâ=â0.003). On-demand sedation was used in 15 patients (6â%) in each group (Pâ=â0.95). CONCLUSIONS: There was no significant reduction in moderate or severe pain in a comparison of water exchange with CO2 insufflation. The secondary outcome of no pain was significantly more frequent in the water exchange group.âClinical trials registry number: NCT01633333.
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Dolor Abdominal/etiología , Dióxido de Carbono , Colonoscopía/métodos , Insuflación/métodos , Agua , Dolor Abdominal/prevención & control , Ciego , Pólipos del Colon/diagnóstico , Colonoscopía/efectos adversos , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Intubación Gastrointestinal , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
Neuroendocrine differentiation of tumor tissue has been recognized as an important prerequisite for new targeted therapies. To evaluate the suitability of colorectal cancer (CRC) tissue for these treatment approaches and to find a possible link to pretherapeutic conditions of other targeted strategies, we compared neuroendocrine differentiation and KRAS/NRAS/BRAF/PIK3CA/TP53 mutational status in primary and metastatic CRC. Immunohistochemical expression analysis of neuroendocrine markers chromogranin A and synaptophysin was performed on archival CRC tissue, comprising 116 primary tumors, 258 lymph node metastases and 72 distant metastases from 115 patients. All CRC samples but 30 distant metastases were subjected to mutation analysis of KRAS, NRAS, BRAF, PIK3CA, and TP53. Neuroendocrine marker expression was found significantly less frequently in lymph node metastases compared to primary tumors and distant metastases (20%, 31%, 28%, respectively, P = 0.044). KRAS mutation rates increased significantly from primary tumors to lymph node metastases and distant metastases within the neuroendocrine negative CRC group (44%, 53%, 64%, respectively, P = 0.042). Neuroendocrine differentiation was significantly less concordant than KRAS/NRAS/BRAF/PIK3CA/TP53 mutational status in primary tumor/lymph node metastases pairs (65% versus 88%-99%; P < 0.0001) and primary tumor/distant metastases pairs (64% versus 83%-100%; P = 0.027 and P < 0.0001, respectively). According to these data, therapeutic targeting of neuroendocrine tumor cells can be considered only for a subset of CRC patients and biopsies from the metastatic site should be used to guide therapy. A possible importance of lacking neuroendocrine differentiation for progression of KRAS mutant CRC should be further investigated.
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Biomarcadores de Tumor/genética , Diferenciación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , GTP Fosfohidrolasas/genética , Proteínas de la Membrana/genética , Mutación , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/secundario , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas/genética , Proteína p53 Supresora de Tumor/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Fosfatidilinositol 3-Quinasa Clase I , Neoplasias Colorrectales/enzimología , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/enzimología , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)RESUMEN
Morphological and clinical heterogeneity of advanced colorectal cancer is probably caused by genetic variability in putative cancer stem cell genes, including Lgr5. Here, we investigated 23 variants of the Lgr5 gene in normal tissue, primary tumors, lymph node metastases and distant metastases of stage III and stage IV colorectal cancer patients. These data were compared to results of immunohistochemical Lgr5 expression analysis and to prognostic clinical parameters. No differences were found comparing germline and somatic Lgr5 genotype in primary tumors, but additional Lgr5 gene alterations could be demonstrated in lymph node and distant metastases. Significant negative correlation was seen between Lgr5 allelic variation and Lgr5 protein expression (p=0.0394), which mainly can be attributed to the negative influence of non-coding Lgr5 gene variations on Lgr5 protein expression (p=0.0166). Lgr5 gene variants could be found more frequently in primary tumors of stage III patients with increased time to recurrence, in distant metastases of patients with better survival and in lymph node metastases of patients with poorer survival compared to patients with Lgr5 wild type in primary and metastatic tissues, respectively. However, the analytic power of these prognostic data was low due to small sample size in the investigated groups. In conclusion, our data indicate that Lgr5 allelic variation affect Lgr5 protein expression in colorectal carcinomas. The somatic Lgr5 genotype seems to be relatively stable in primary tumors, but becomes vulnerable during the metastatic process of colorectal cancer. This instability has possibly prognostic importance, which has to be further evaluated by large cohort studies.
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The recently advanced cancer stem cell model postulates that progression and metastasis of cancer are mainly driven by tumor cells with stem cell properties. Intestinal cancer stem cells are difficult to study due to the lack of reliable markers, but expression of the Wnt target gene Lgr5 is promising to define at least stem cell like cells in intestinal and colorectal cancer. The aim of this study was to find a possible link of stem cell like cancer cells to the metastatic process of colorectal cancer. To this end, we evaluated immunohistochemical Lgr5 expression in 31 distant metastases and in primary tumor compartments with relevance for metastasizing, comprising 89 colorectal carcinomas. Lgr5 expression was seen in 51.6% of distant metastases. 12.9%, 14.8% and 26.7% of primary tumors with histologically confirmed tumor buds, angioinvasion and perineural infiltrates, respectively, showed evidence of Lgr5 expression in these tumor compartments. However, distant metastases, which were derived from carcinomas with such Lgr5 positive tumor compartments, showed 6- to 11.5-fold higher median value of Lgr5 expression compared to those metastases derived from tumors without Lgr5 expressing cells in these compartments. These differences between the metastases were statistically significant, if being related to tumor buds (all tumors; p = 0.047) and to vascular infiltrates (stage IV tumors; p = 0.007). In conclusion, our results point to rare evidence of Lgr5 positive stem cell like cells in the metastatic cascade of colorectal cancer, but these few cells might be biologically powerful in the metastatic process of cancer subsets. Clonal analysis is necessary to proof this hypothesis.
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Biomarcadores de Tumor/análisis , Carcinoma/química , Neoplasias Colorrectales/química , Células Madre Neoplásicas/química , Receptores Acoplados a Proteínas G/análisis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/secundario , Carcinoma/terapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , PronósticoRESUMEN
Alterations in the p16/cyclinD1/Rb and ARF/Mdm2/p53 pathways are frequent events in the pathogenesis of squamous cell carcinomas. Different mechanisms of p16 regulation have been described for penile carcinomas so far. Therefore, expression of p16 and p53 was immunohistochemically detected with monoclonal antibodies in 52 primary invasive penile squamous cell carcinomas. The carcinomas were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for mutations in the p16(INK4A) and the p53 gene. In addition, we examined the promoter status of p16(INK4A) by methylation-specific PCR. The presence of human papilloma virus (HPV) 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Data were compared to clinical data. Concerning p16, 26 (50%) tumors showed positive immunohistochemistry, 32 (62%) tumors showed allelic loss and 22 tumors (42%) showed promoter hypermethylation. All tumors with negative p16 immunohistochemistry showed LOH near the p16(INK4A) locus and/or hypermethylation of the p16(INK4A) promoter. HPV 16 DNA was detected in 17 tumors, ten of them with positive p16 immunostaining. The remaining seven tumors with negative p16 staining showed allelic loss and/or promoter hypermethylation. Evidence of lymph node metastasis was significantly associated with negative p16 immunohistochemistry as well as with combined LOH and promoter hypermethylation (p = 0.003 and p = 0.018, respectively). Allelic loss around p53 was found in 22 tumors (42%), and seven mutations of the p53 gene could be demonstrated in our tumors. No correlations could be found between any p53 alteration and clinical parameters.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Genes p16 , Neoplasias del Pene/genética , Neoplasias del Pene/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/virología , Metilación de ADN , ADN Viral/análisis , Genes p53/genética , Humanos , Inmunohistoquímica , Pérdida de Heterocigocidad , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Neoplasias del Pene/virología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Gastrointestinal stromal tumors sometimes occur together with gastric carcinoma, but true collision tumors featuring these 2 components are very rare. The authors describe here 2 collision tumors containing a gastrointestinal stromal tumor with intermingling elements of gastric adenocarcinoma. The gastrointestinal stromal tumors were 5.5 to 6 cm spindle cell tumors, and one patient had an additional prepyloric stromal tumor (2.5 cm). All gastrointestinal stromal tumors had low mitotic counts less than 5/50 high-power fields and were positive for KIT, DOG1, and CD34. Different KIT exon 11 mutations (single nucleotide substitution, complex insertion-duplication) in all tumors indicated that the 2 gastrointestinal stromal tumors in one patient were independent primary tumors. The adenocarcinoma components displayed gland-forming intestinal type to signet ring cell morphology with focally accompanying dysplastic epithelium, immunohistochemical positivity for CDX2, and varying keratin 7/20 expression. We hypothesize that development of gastric adenocarcinoma within a gastrointestinal stromal tumor may be based on displaced gastric epithelium in a long-standing stromal tumor with events of intermittent ulceration and epithelial regeneration.
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Adenocarcinoma , Tumores del Estroma Gastrointestinal , Neoplasias Primarias Múltiples , Neoplasias Gástricas , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Anoctamina-1 , Antígenos CD34/metabolismo , Canales de Cloruro , Resultado Fatal , Femenino , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/patología , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Mutación , Proteínas de Neoplasias/metabolismo , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Primarias Múltiples/patología , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
Penile cancer, observed only rarely in the western world, represents a carcinoma that may be cured by resection of primary lesion and in case of lymph node metastasis by early lymph node dissection. This early inguinal lymphadenectomy bares a significant better survival even in cases of nonpalpable lymph nodes, but carries also a high risk of overtreatment, especially in lower tumor stages. Due to the low incidence, only few data are available on the molecular genetic background of this tumor, especially concerning tumor progression and metastasis. Therefore, we studied 62 microsatellite markers in 28 penile carcinomas searching for markers predicting progression or outcome. LOH in more than 25% of primary tumors was found on six different chromosomes, including 2q, 6p, 8q, 9p, 12q and 17p13. Statistically significant correlations could be established in D6S260 to clinical outcome and in markers from chromosomes 6, 9 and 12 to tumor stage and metastasis. These regions are worthy for further analysis concerning tumor suppressor genes and metastasis suppressor genes.
Asunto(s)
Carcinoma de Células Escamosas/genética , Inestabilidad de Microsatélites , Repeticiones de Microsatélite/genética , Neoplasias del Pene/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , ADN de Neoplasias/análisis , Marcadores Genéticos , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Neoplasias del Pene/mortalidad , Neoplasias del Pene/patología , Neoplasias del Pene/cirugía , Pronóstico , Tasa de SupervivenciaRESUMEN
Deletions on the long arm of chromosome 15 suggesting the presence of potential tumor suppressor genes have been found in several tumors including carcinomas of the colorectum, urinary bladder, breast, lung, and head and neck. Here, we analyzed allelic imbalance on chromosome 15q in head and neck carcinomas and corresponding lymph node metastases to define common regions of aberrations with potential involvement in development and progression of these tumors. We studied a panel of 40 polymorphic microsatellite markers, spanning 15q13-15q26, in 63 head and neck carcinomas and 38 lymph node metastases. Loss of heterozygosity (LOH) could be demonstrated in 34 primary tumors (54%) and 35 metastases (92%). Aberration mapping defined three minimum regions of aberrations: a region between the markers D15S106 and D15S1029 in 15q21.3 (estimated as 3.9 Mb; region 1) was affected in the majority of tumors, whereas two other regions between D15S144 and D15S1040 in 15q13.3-14 (estimated as 2.4 Mb; region 2) and between D15S130 and D15S985 in 15q26.2-26.3 (estimated as 4.7 Mb; region 3) were less often involved. Allelic loss in region 1 correlated with T stages (P=0.0029) and metastatic potential (P=0.0018). LOH in regions 2 and 3 occurred predominantly in metastases (P=0.0129 and P=0.0013, respectively). No correlation with grading, localization, or clinical outcome could be established for any of the affected regions. Our data hint at aberrations in 15q21.3 as a possible important characteristic for head and neck squamous cell carcinomas with risk of progression.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundario , Cromosomas Humanos Par 15/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Pérdida de Heterocigocidad , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
A comparative proteomic analysis of neoplastic versus non-neoplastic seminoma identified glutathione S-transferase M3 as a differentially expressed protein. This expression difference could also be observed at the mRNA level, implying neoplasm-associated alterations in transcriptional or post-transcriptional mechanisms.
Asunto(s)
Células Germinativas/enzimología , Glutatión Transferasa/metabolismo , Seminoma/enzimología , Neoplasias Testiculares/enzimología , Biomarcadores/análisis , Biomarcadores/metabolismo , Electroforesis en Gel Bidimensional , Regulación Neoplásica de la Expresión Génica , Células Germinativas/citología , Glutatión Transferasa/análisis , Glutatión Transferasa/genética , Humanos , Masculino , Espectrometría de Masas , Proteómica , ARN Mensajero/metabolismo , Transcripción GenéticaRESUMEN
Pleomorphic adenoma (PA), being the most common benign tumor of the salivary glands, is composed of epithelial and mesenchymal compartments. In this study, we analyzed 19 microsatellite markers from chromosomal arms 6q, 8q, 9p, 12q, and 17p in 31 PAs and 3 carcinoma ex pleomorphic adenomas (CXPAs) as well as 11 other non-PA-related carcinomas of the salivary gland for comparison. In our analysis, we differentiated between epithelial and mesenchymal tissues. Loss of heterozygosity (LOH) in PAs was most often found in 8q (32%) and 12q (29%). Two of the three CXPAs displayed allelic loss at all chromosomal arms investigated, whereas the results of the non-PA-related carcinomas were rather heterogeneous. LOH could not only be detected in the epithelial, but also in the mesenchymal, compartments of a subset of PAs, especially at chromosomal arm 8q. Concerning the CXPAs, we were able to demonstrate allelic losses not only in the malignant epithelial compartment, but also in the residual adenoma parts. Our data give further evidence that alterations in 8q may be an early event in PA tumorigenesis, whereas LOH in 12q may characterize cells with the potential to transform in CXPAs.
Asunto(s)
Adenoma Pleomórfico/genética , Adenoma Pleomórfico/patología , Pérdida de Heterocigocidad , Repeticiones de Microsatélite , Neoplasias de las Glándulas Salivales/genética , Adenoma Pleomórfico/metabolismo , Adolescente , Adulto , Anciano , Alelos , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 8 , ADN/metabolismo , Epitelio/patología , Femenino , Humanos , Masculino , Mesodermo/patología , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patologíaRESUMEN
Archival pathology specimens are nowadays a frequently used source in forensic identification or paternity testing, if no other material is available. A greater part of this archived material, however, consists of solid tumors known for aberrations in coding and non-coding regions of the genome. Therefore, alterations of short tandem repeats (STRs) used in forensic casework are also possible. In our study of 118 solid tumors, 46 lymph node metastases, and 16 distant metastases with the AmpFlSTR trade mark Profiler Plus PCR amplification kit comprising nine STR loci, we detected four kinds of changes between normal and tumor tissue: partial loss of one allele (pLOH), complete loss of one allele (LOH), occurrence of an additional allele and occurrence of a new allele instead of that found in normal tissue. Twenty-two percent of the tumor lesions displayed pLOH, but only in 14% one allele was completely lost. New alleles could be demonstrated in 18% of tumors, and in 8% the new allele in the tumor tissue replaced the one found in normal tissue. The changes were distributed over all nine STRs, but the STRs mostly affected were FGA, D3S1558, D18S51 and D21S11. The occurrence of new alleles in the tetra-nucleotide repeats correlated mainly with microsatellite instability in di-nucleotide and mono-nucleotide repeats. The occurrence of new alleles was most frequent in primary tumors of colon carcinomas and HNSCC metastases. In melanomas, only loss of alleles could be found. Our results demonstrate that the use of tumor tissue in forensic identification and paternity testing is questionable, especially if only tumors with known microsatellite instability are available.