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Fernando López-Ríos

Publications and source records attributed to Fernando López-Ríos.

10 recordsLinked to original sources
PubMed2006

Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction.

Most gene expression profiling studies of mesothelioma have been based on relatively small sample numbers, limiting their statistical power. We did Affymetrix U133A microarray analysis on 99 pleural mesotheliomas, in which multivariate analysis showed advanced-stage, sarcomatous histology and P16/CDKN2A homozygous deletion to be significant independent adverse prognostic factors. Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry. Examination of the gene expression correlates of survival showed that more aggressive mesotheliomas expressed higher levels of Aurora kinases A and B and functionally related genes involved in mitosis and cell cycle control. Independent confirmation of the negative effect of Aurora kinase B was obtained by immunohistochemistry in a separate patient cohort. A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors. We then used our data to develop microarray-based predictors of 1 year survival; these achieved a maximal accuracy of 68% in cross-validation. However, this was inferior to prognostic prediction based on standard clinicopathologic variables and P16/CDNK2A status (accuracy, 73%), and adding the microarray model to the latter did not improve overall accuracy. Finally, we evaluated three recently published microarray-based outcome prediction models, but their accuracies ranged from 63% to 67%, consistently lower than reported. Gene expression profiling of mesotheliomas is an important discovery tool, but its power in clinical prognostication has been overestimated.

Adult↗
PubMed2005

Pulmonary vascular remodeling in pulmonary hypertension due to chronic heart failure.

UNLABELLED: Pulmonary hypertension (PHT) associated with chronic heart failure (CHF) is a risk factor of right ventricular failure after heart transplantation (HT). Our aim was to study pulmonary vascular changes in patients with CHF and to assess any correlation with haemodynamic data. METHODS: We studied 17 HT recipients with preoperative CHF who died shortly after HT. Preoperative haemodynamic information was obtained immediately before HT. Vascular lesions in muscular arteries were assessed by linear morphometry. Haemodynamic data were correlated with the morphologic changes. RESULTS: Mean transpulmonary gradient (TPG) was 8.9+/-4.5 mm Hg and pulmonary vascular resistance (PVR) was 2.25+/-1.34 Wu. According to the threshold for at-risk PHT (TPG>12 mm Hg or PVR>2.5 Wu), six patients had at-risk PHT. Medial thickness was 23.82+/-7.23% in patients with at-risk PHT and 17.16+/-3.24% in patients without at-risk PHT (p=0.018). CONCLUSIONS: Medial hypertrophy of muscular pulmonary arteries is more common and severe than expected in patients with CHF, even in patients without at-risk PHT. This structural change could explain why PHT, even in range of values not excluding HT, is a risk factor for right ventricular failure after HT and influences post-HT haemodynamic behaviour.

Adult↗
PubMed2002

Fine-needle aspiration biopsy of the retroperitoneum: a series of 111 cases not including specific organs.

We report on our experience in fine-needle aspiration (FNA) biopsy of the retroperitoneum: 111 FNA biopsies performed on 99 patients. Cytologic diagnoses were divided into four groups: nondiagnostic (unsatisfactory samples because of a low cellularity and/or improperly prepared smears) aspirates (20%), benign (16%), suspicious for malignancy (13%), and malignant (50%). There were no known false-positive samples. We had two false-negative diagnoses due to sampling errors. Among diagnostic smears, the procedure showed a sensitivity of 97% and a specificity of 100%. The predictive value of a positive result was 100% and the predictive value of a negative result was 90%. The overall accuracy was 98%. Metastatic carcinomas accounted for the largest number of lesions in the group of malignant tumors. A primary tumor site was known for the majority of the cases before the aspiration was performed. In the remaining cases we were unable to suggest an origin. It is therefore important to emphasize the role of ancillary studies in patients that are at the first assessment of the disease or when a second intercurrent malignancy is suspected. In our limited experience, a suggestion of the correct subtype of retroperitoneal sarcoma was not possible. As in the rest of cytopathology, a multidisciplinary approach is mandatory in this setting to improve patient management.

Adult↗
PubMed2002

Keratinocyte dysplasia: an usual finding after transplantation or chemotherapy.

BACKGROUND: Keratinocyte dysplasia is a histologic abnormality that has rarely been described in the first weeks after chemotherapy or transplantation. The purpose of this study was to determine the prevalence of early keratinocyte dysplasia after chemotherapy or transplant and to analyze the relationship between dysplasia and chemotherapeutic agents, transplantation or development of acute graft vs. host disease (GvHD). METHODS: A computer search for transplant patients was performed in the Departments of Hematology, Oncology and Surgery. Only patients with a skin biopsy taken within the first days of transplantation or chemotherapeutic treatment were included in the analysis. RESULTS: Forty-four patients were included, of these 19 were women and 25 were men. Thirty-four (77.3%) of 44 biopsies showed keratinocyte dysplasia. This dysplasia was severe in 18 cases (40.9%). Cyclophosphamide was more likely to be associated with severe keratinocyte maturation disturbances (OR = 5.51) (p < 0.01) whereas cytarabine was associated with a lower risk (OR = 0.19) (p < 0.05). CONCLUSIONS: Severe keratinocyte dysplasia is a usual histologic finding in patients who have received chemotherapy and/or transplantation (40.9%). Cyclophosphamide is the main chemotherapeutic agent significantly associated with a higher risk of severe dysplasia (OR = 5.51). Causes other than GvHD or preconditioning treatment may be involved in the keratinocyte dysplasia, as it can be also found in transplanted patients who have not received chemotherapy and/or have not developed GvHD.

Adolescent↗
PubMed2002

Trichoblastoma arising within an apocrine poroma.

A poroma is a benign neoplasm composed of poroid and cuticular cells and is thought to derive from the eccrine duct. Several recent reports have described cases with sebaceous, follicular, and apocrine differentiation, suggesting a possible apocrine origin, however. Trichoblastoma is a rare benign tumor composed of germinative cells related to the folliculosebaceous-apocrine unit. We report a unique case of a trichoblastoma arising within a poroma with apocrine and sebaceous differentiation. To our knowledge, this exceptional association has not been described previously and may support the theory of the apocrine origin of poromas.

Acrospiroma↗
PubMed2002

Human papillomavirus-negative spindle cell carcinoma of the vulva associated with lichen sclerosus: case report and literature review.

Although spindle cell carcinoma (SC) is a common neoplasm in the oral cavity, upper respiratory tract, and other head and neck areas, its occurrence in the vulva is rare. We report a case of this rare condition with immunohistochemical, ultrastructural, and human papillomavirus (HPV) testing. The neoplastic cells were positive for vimentin, keratins (AE1-AE3, keratin 902, and keratin 903), and epithelial membrane antigen. Ultrastructurally, they showed primitive junctions and tonofilaments. HPV testing by polymerase chain reaction was negative. In addition, we review the clinicopathologic findings of the four well-documented cases of vulvar SC that have been reported previously in the English language literature.

Aged↗
PubMed2002

Plexiform fibrohistiocytic tumor without multinucleated giant cells: a case report.

Plexiform fibrohistiocytic tumor (PFT) is a rare but distinctive soft tissue tumor of children and young adults characterized by a mixture of histiocyte-, myofibroblast-, and osteoclast-like giant cells arranged in a plexiform pattern. We report the clinicopathologic and immunohistochemical features of an apparently unique case of PFT without multinucleated giant cells presenting in a 3-year-old child. Light microscopy revealed a subcutaneous tumor composed of a plexiform proliferation of histiocyte- and myofibroblast-like cells. Multinucleated osteoclast-like giant cells, the third classic cellular component of this mesenchymal neoplasm, were not observed. The differential diagnosis is also discussed. Emphasis is placed on the importance of the recognition of PFT, because it may exhibit an aggressive behavior.

Biomarkers, Tumor↗
PubMed2002

Mitotically active juvenile xanthogranuloma.

Juvenile xanthogranuloma is a histiocytic inflammatory disorder capable of presenting different histologic patterns. The classic form consists of sheets of foamy histiocytes and numerous multinucleated Touton-type giant cells containing no to very few mitotic figures. Nonlipidized juvenile xanthogranuloma consists of a diffuse monomorphic histiocytic infiltrate and usually shows a slightly higher mitotic index. Histologic hematoxylin-eosin staining techniques were used after excision of a pink ulcerated nodule in a 2-year-old girl. Histopathologic examination showed a nonencapsulated cellular proliferation mainly occupying dermis, but extending into the subcutaneous tissue as well. Most of the cells were epithelioid histiocytes, but foamy and Touton giant cells were also evident. The most striking feature was the presence of a high number of mitotic figures, as many as 23 per 10 high-power fields. We present an unusual case of classic juvenile xanthogranuloma with areas similar to those found in the nonlipidized type and with a high mitotic index.

Child, Preschool↗
PubMedDate not supplied

Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids.

BACKGROUND: PCR-based evidence of infection by simian virus 40 (SV40) has been reported in varying proportions of pleural mesotheliomas and other tumours, but data are conflicting and reproducibility limited. During a study of SV40 in relation to homozygous deletion of CDKN2A in mesotheliomas, we became concerned by inconsistent results and therefore used several independent techniques to investigate SV40 in these tumours. METHODS: High-quality DNA and RNA were extracted from 71 frozen mesothelioma samples. DNA PCR was done with four sets of primers for the SV40 T-antigen gene. RNA transcripts were examined by RT-PCR. FINDINGS: The first two primer sets for DNA PCR gave positive results in proportions similar to those reported in positive studies (56-62%) but there were unusual reproducibility difficulties. These primers were in a region of the T-antigen gene (nucleotides 4100-4713) that is present in many common laboratory plasmids. In assays with PCR primers not included within that region, only four cases (6%) showed products but these were too faint to suggest clonal infection. Further PCR assays confirmed that the SV40 sequences in the tumour samples had a deletion found only in plasmids, not in native functional SV40. Review of previous studies showed a similar pattern of discrepancies between SV40 T-antigen DNA PCR results obtained with primers within and beyond the region 4100-4713. All 71 mesotheliomas were negative for T-antigen transcripts by RT-PCR, and lacked T-antigen-positive tumour cells by immunohistochemistry. INTERPRETATION: Our data based on three independent experimental approaches do not support a significant role for SV40 in human mesotheliomas. The risk of false-positive results due to contamination by common laboratory plasmids containing SV40 sequences has been underestimated. Studies of SV40 based on PCR methods require careful primer design to reduce this risk. RELEVANCE TO PRACTICE: This paper presents several lines of evidence against the proposed link between SV40 infection and human mesotheliomas. Studies reporting a high prevalence of SV40 DNA in human tumours have been based on molecular assays prone to false-positive results. Because SV40 appears unlikely to have a major role, if any, in human mesotheliomas, clinicians should continue to consider asbestos exposure as the most likely and most thoroughly established aetiological factor in individuals with this cancer.

Adult↗