Biomedical subjects

Enrique Lerma

Publications and source records attributed to Enrique Lerma.

14 recordsLinked to original sources

PubMed2006

Expression profiles associated with aggressive behavior in Merkel cell carcinoma.

Primary neuroendocrine carcinoma of the skin, or Merkel cell carcinoma, is the most aggressive cutaneous neoplasm. In spite of its similarities to small cell carcinomas from other locations, Merkel cell carcinoma shows many peculiarities probably related to its epidermal origin and the etiologic role of UV radiation. We have immunohistochemically investigated 43 markers on a tissue microarray in which 31 surgically resected Merkel cell carcinomas were represented. Of these, 15 patients remained free of disease after removal, whereas 16 developed metastases. Immunoreactivity was scored according to staining intensity and the percentage of positive cells. We found statistically significant correlations between metastatic tumor spread and overexpression of matrix metalloproteinase (MMP) 7, MMP10/2, tissue inhibitor of metalloproteinase 3, vascular endothelial growth factor (VEGF), P38, stromal NF-kappaB, and synaptophysin. Also detected were statistically significant correlations between the expression levels of MMP7 and VEGF, MMP7 and P21, MMP7 and P38, MMP10/2 and VEGF, P38 and synaptophysin, P38 and P53, and P21 and stromal NF-kappaB. These findings may be helpful in predicting the clinical course of Merkel cell carcinoma and are potentially useful for the development of targeted therapies.

Biomarkers, Tumor↗

PubMed2006

PTEN promoter methylation in sporadic thyroid carcinomas.

The tumor-suppressor gene PTEN/MMAC1, on chromosome 10q23.3, has been implicated in an important number of human tumors, such as thyroid carcinomas. PTEN somatic mutations occur in sporadic tumors of the endometrium, brain, prostate, or melanomas, while germline mutations predispose to development of the multiple hamartoma syndromes (i.e., Cowden's disease and Bannayan-Zonana syndrome). Activation of the two alleles of PTEN is required for its tumor-suppression role. Because the frequency of PTEN suppression in thyroid tumors exceeds that of PTEN mutations or deletions, it is very likely that epigenetic mechanisms, such as promoter hypermethylation, may account for its inactivation in a subset of tumors. The main aim of this study was to assess the frequency of promoter hypermethylation of PTEN in thyroid tumors. We studied frozen tissue samples from 46 papillary carcinomas, 7 follicular carcinomas, 6 follicular adenomas as well as 39 normal thyroid tissue samples. Methylation-specific polymerase-chain reaction (PCR) with three different sets of primers was used. Two of the primer sets were designed to avoid any interference with PTEN pseudogene promoter. PTEN promoter hypermethylation was detected in 21 of 46 (45.7%) papillary carcinomas, 6 of 7 follicular carcinomas, and 5 of 6 follicular adenomas. It was negative in all normal tissues. Negative immunohistochemical staining for PTEN was significantly associated with the presence of promoter hypermethylation (p < 0.001). These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis.

Adenoma↗

PubMed2005

Telomerase activity in "suspicious" thyroid cytology.

BACKGROUND: Telomerase activity (TA) has been detected in most malignant neoplasms, including thyroid carcinomas. The authors studied the utility of TA detection as an ancillary tool to thyroid fine-needle aspiration (FNA) for patients with nonconclusive cytologic diagnoses. METHODS: Material obtained by FNA from palpable thyroid nodules in 167 consecutive patients was processed for conventional cytologic studies and simultaneously for TA study. Another 8 patients were excluded from TA because of the presence of lymphocytes. All patients with negative results cases were followed for > 1 year, and those who had tumors that were suspicious or positive by FNA or TA underwent resection for pathologic study of nodules. TA was analyzed by telomere repeat amplification protocol-polymerase chain reaction analysis. RESULTS: After excluding 20 patients because of insufficient material for cytologic study, 120 patients had negative results for malignant cells in cytology material, and the remaining 27 patients had results that were either suspicious (n = 21 patients) or positive (n = 6 patients). Histopathologic confirmation was obtained in 23 patients, including 18 with suspicious cytology (1 with scanty material) and 5 with positive FNA. The histopathologic diagnoses were nodular hyperplasia in 5 patients, follicular adenoma in 3 patients, papillary carcinoma in 11 patients, follicular carcinoma in 1 patient, medullary carcinoma in 2 patients, and lymphoma in 1 patient. TA was detected in 6 of 18 histologically confirmed thyroid neoplasms (1 of 3 follicular adenomas, 3 of 11 papillary carcinomas, 0 of 1 follicular carcinoma, 1 of 2 medullary carcinomas, and 1 of 1 lymphoma), including 1 neoplasm with scanty atypical cells. CONCLUSIONS: The detection of TA helped to confirm neoplasia in 6 of 23 suspicious thyroid nodules. Although it was less sensitive than FNA, TA specificity was 100% for neoplasia and 87.5% for malignancy. The sensitivity of thyroid FNA increased with the use of TA detection when cytology was nonconclusive for malignancy.

Adenocarcinoma, Follicular↗

PubMed2005

Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.

PURPOSE: Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. MATERIALS AND METHODS: We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. RESULTS: We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.

Acid Anhydride Hydrolases↗

PubMed2005

Lupus panniculitis involving the breast.

Lupus panniculitis is an unusual immunological disease that characteristically affects the subcutaneous fat and occurs in 2% of patients with systemic lupus erythematosus. We report a case of lupus panniculitis involving the breast, which represents a very uncommon location. Mammographically, it presented as a suspicious irregular mass involving the subcutaneous fat pad with skin thickening. High echogenicity constituted the most relevant sonographic finding. To the best of our knowledge, the magnetic resonance (MR) features have not been previously described. High signal intensity was found on both T1- and T2-weighted precontrast MR images. A dynamic contrast-enhanced study revealed a suspicious focal mass with irregular margins and rim enhancement, with a type 3 time-signal intensity curve. Differential diagnosis with carcinoma and fat necrosis and the value of core biopsy are discussed.

Adrenal Cortex Hormones↗

PubMed2005

[BRCA1 and BRCA2 mutations in patients with familial breast cancer].

BACKGROUND AND OBJECTIVE: Familial breast (BC) and ovarian cancer (OC) has been associated with germ-line mutations in the cancer susceptibility genes BRCA1 and BRCA2. The mutational spectra vary depending on the study populations and the criteria applied for patient selection. The present study reports the mutations found in 48 families of the Valencian Community studied in the University Hospital La Fe of Valencia (Spain). PATIENTS AND METHOD: We analysed the BRCA1 and BRCA2 genes of 48 families (55 patients) with a family history of BC an/or OC. The method consists of DNA extraction, followed by a polymerase chain reaction, mutational analysis by heteroduplex formation in conformation-sensitive-gel electrophoresis and sequencing of the heteroduplex detected. RESULTS: We report eight different deleterious mutations, four in BRCA1 and four in BRCA2 and four unclassified variants (UV). We also identified the presence of the BRCA1 3889_3890delG mutation for the first time in the Spanish population. In BRCA2, we report two mutations not described in the breast cancer information care, the 5025delT which is completely new and the 9206_9219del14, which has already been described in Spanish population. We also describe for the first time the presence of UV 8038C>T in this gene. CONCLUSIONS: The mutational spectra and the presence of new mutations in the limited number of patients give support to the relevance of the study population in the mutational spectra.

Adult↗

PubMed2005

Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers.

Familial breast cancers that are associated with BRCA1 or BRCA2 germline mutations differ in both their morphological and immunohistochemical characteristics. To further characterize the molecular difference between genotypes, the authors evaluated the expression of 37 immunohistochemical markers in a tissue microarray (TMA) containing cores from 20 BRCA1, 14 BRCA2, and 59 sporadic age-matched breast carcinomas. Markers analyzed included, amog others, common markers in breast cancer, such as hormone receptors, p53 and HER2, along with 15 molecules involved in cell cycle regulation, such as cyclins, cyclin dependent kinases (CDK) and CDK inhibitors (CDKI), apoptosis markers, such as BCL2 and active caspase 3, and two basal/myoepithelial markers (CK 5/6 and P-cadherin). In addition, we analyzed the amplification of CCND1, CCNE, HER2 and MYC by FISH. Unsupervised cluster data analysis of both hereditary and sporadic cases using the complete set of immunohistochemical markers demonstrated that most BRCA1-associated carcinomas grouped in a branch of ER-, HER2-negative tumors that expressed basal cell markers and/or p53 and had higher expression of activated caspase 3. The cell cycle proteins associated with these tumors were E2F6, cyclins A, B1 and E, SKP2 and Topo IIalpha. In contrast, most BRCA2-associated carcinomas grouped in a branch composed by ER/PR/BCL2-positive tumors with a higher expression of the cell cycle proteins cyclin D1, cyclin D3, p27, p16, p21, CDK4, CDK2 and CDK1. In conclusion, our study in hereditary breast cancer tumors analyzing 37 immunohistochemical markers, define the molecular differences between BRCA1 and BRCA2 tumors with respect to hormonal receptors, cell cycle, apoptosis and basal cell markers.

Adult↗

PubMed2003

Immunohistochemical characteristics defined by tissue microarray of hereditary breast cancer not attributable to BRCA1 or BRCA2 mutations: differences from breast carcinomas arising in BRCA1 and BRCA2 mutation carriers.

PURPOSE: Most familial breast cancers are not associated with BRCA1 or BRCA2 germ-line mutations. Therefore, it is of major importance to define the morphological, immunohistochemical, and molecular features of this group of tumors to improve genetic testing and also gain further insight into the biological characteristics of tumors. EXPERIMENTAL DESIGN: We evaluated the morphological characteristics of 37 tumors arising in women without BRCA1 or BRCA2 mutations, 20 tumors from BRCA1 mutation carriers, and 18 from BRCA2 mutation carriers, all of which were from index patients from breast cancer families. In addition, a tissue microarray was constructed with all tumoral samples to evaluate the immunohistochemical expression of a wide panel of antibodies (11 antibodies) and the amplification of HER-2 and c-MYC genes by fluorescence in situ hybridization. An age-matched group with 50 sporadic breast cancers as controls for non-BRCA1/2 was also included. RESULTS: Non-BRCA1/2 infiltrating ductal carcinomas (IDCs) showed specific differences from BRCA1 tumors. They were of lower grade (1 and 2); more frequently estrogen receptor, progesterone receptor, BCL2 positive, and p53 negative; had a low proliferation rate (Ki-67 immunostaining < 5%); and did not express P-cadherin. With respect to BRCA2 IDCs and control group, non-BRCA1/2 tumors were of lower grade and had a lower proliferation rate. No cases of HER-2 amplification and/or overexpression were observed except in the control group ( approximately 20%). In contrast, c-MYC amplification was present in 18.2, 62.5, and 12.5% of BRCA1, BRCA2, and non-BRCA1/2 IDCs, respectively, and 31% in the control group. CONCLUSIONS: This study thus reveals distinct morphological and immunohistochemical features in non-BRCA1/2 and BRCA1 tumors, whereas BRCA2 tumors present characteristics intermediate between the two phenotypes. In addition, the study also demonstrates the usefulness of tissue microarray technology in the evaluation of the immunophenotypic features of hereditary breast cancer.

Adult↗

PubMed2003

Diagnosis and grading of chondrosarcomas on FNA biopsy material.

A consecutive series of 47 chondrosarcomas was reviewed to identify the most useful criteria for cytological diagnosis, and grading in comparison to histology grade. This series includes 39 evaluable cases, including 2 patients with Ollier's disease and 2 with extraskeletal chondrosarcomas. Eight cases were excluded because of lack of histologic confirmation (3). nondiagnostic cytology (4). and one inconclusive histologic diagnosis. The cytologic diagnosis of these tumors was based on the identification of chondrocytes and a chondromyxoid stroma. The chondrocytes often showed double nuclei (34/39) and macronucleoli (20/39). Nuclear atypia in terms of distinct variation in size was less common (16/39). Cytoplasmic granules and vacuoles were often seen (34/39 and 29/39, respectively). In smears, chondroid fragments and a chondromyxoid background were seen in a majority of cases (36/39 and 30/39, respectively). By grade, concordance with histology was present in 4/7 grade I tumors, 26/29 grades II-III, and 5/5 grade IV, respectively.

Adolescent↗

PubMed2002

Histologic findings after amniotic membrane graft in the human cornea.

OBJECTIVE: To describe the histopathologic findings in the human cornea several months after a stromal amniotic membrane graft. To show the clinicopathologic correlation after the graft in two cases with different follow-up times. DESIGN: Two interventional case reports with clinicopathologic correlation. PARTICIPANTS: Two patients with neurotrophic corneal ulcer unresponsive to medical treatment (one with stromal vascularization and the other without stromal vascularization). INTERVENTION: Amniotic membrane graft was performed in both patients to treat the neurotrophic ulcer. Three and 7 months after amniotic membrane grafting, a penetrating keratoplasty was needed, and the removed corneas were analyzed. MAIN OUTCOME MEASURES: Clinical and histopathologic examinations, including routine histopathologic and immunohistochemical studies. RESULTS: Complete epithelialization was observed on histologic examination over the basement membrane of the amniotic membrane graft. The amniotic membrane was slowly reabsorbed in the cornea without stromal vascularization with no inflammatory reaction produced. In the cornea that had stromal vascularization the amniotic membrane was rapidly reabsorbed because of the presence of abundant inflammatory cells. Once reabsorbed, the amniotic membrane was replaced by new fibrotic stroma, that was different from that found in the rest of the cornea but that helped to maintain corneal thickness. CONCLUSIONS: The amniotic membrane graft allows for correct epithelialization in cases of neurotrophic corneal ulcer. Once the amniotic membrane is reabsorbed, it is replaced by a new fibrotic stroma, which can reduce corneal transparency. In corneas that have no stromal vascularization, the graft may remain in the stroma for many months, compromising corneal transparency during this period.

Aged↗

PubMed2002

Alterations of the p16/Rb/cyclin-D1 pathway in vulvar carcinoma, vulvar intraepithelial neoplasia, and lichen sclerosus.

Three different alterations in the p16/pRb/cyclin-D1 pathway (p16(INK4a)-promoter hypermethylation and expression of pRb and cyclin-D1) were investigated in a series of 38 cases of vulvar carcinoma (VC), 13 cases of vulvar intraepithelial neoplasia (VIN), and 21 cases of lichen sclerosus (LS). Paraffin blocks from 72 patients were selected for investigation of DNA methylation patterns in the CpG island of p16(INK4a) by methylation-specific polymerase chain reaction. Immunohistochemical studies for pRb and cyclin-D1 were performed using the standard avidin-biotin-peroxidase complex method. Epigenetic silencing of p16(INK4a) was detected in 68% of VC, 69.2% of VIN, and 42.8% of LS cases. Lack of pRb protein was found in 21% of VC, 0% of VIN, and 0% of LS cases. Overexpression of cyclin-D1 was found in 21% of VC, 30.8% of VIN, and 0% of LS cases. We conclude (1) that p16(INK4a) epigenetic inactivation most likely represents an early event, insufficient for malignant transformation, that may occur in clinically benign lesions such as LS; (2) that lack of pRb was only detected in fewer than one quarter of the carcinomas and could be considered a late secondary event; and (3) that cyclin-D1, which was overexpressed in VC and VIN, could contribute to the malignant transformation in association with p16 hypermethylation.

Adult↗

PubMed2002

Rapid quantitative detection of TEL-AML1 fusion transcripts in pediatric acute lymphoblastic leukemia by real-time reverse transcription polymerase chain reaction using fluorescently labeled probes.

BACKGROUND AND OBJECTIVES: We report a new real-time reverse transcription polymerase chain reaction (RT-PCR) method for quantification of TEL-AML1 transcripts. The method is based on hybridization probe (HybProbe) chemistry applied in LightCycler equipment. The study group comprised 44 successive cases of pediatric acute lymphoblastic leukemia (P-ALL). DESIGN AND METHODS: The quantitative estimation of TEL-AML1 transcripts was performed in 10 P-ALL TEL-AML1-positive patients. The PCR was performed in capillary tubes in 10 microL final volumes using two sets of primers: M1, which detects the long (L-form) and short (S-form) transcripts, and M2, specific for the L-form. The fluorescently labeled HybProbes (TEL 3FL and TEL 5LC) hybridize to the TEL region. TEL-AML1 expression was normalized relative to the levels of AML1 transcripts. Standard curves were prepared using serial dilutions of plasmids with TEL-AML1 or AML1 inserts. RESULTS: The sensitivity attained allowed the detection of TEL-AML1 transcripts at a 10-4 dilution of a cDNA sample from a patient at diagnosis. The within-assay coefficient of variation (CV) for TEL-AML1 was 7.0% and the between-assay CV was 13%. Levels of TEL-AML1 transcript and the TEL-AML1/AML1 ratio decreased by more than four log units (p <0.001) during or after the course of initial treatment. Most of the patients who achieved complete remission after 5-6 months of initial treatment were TEL-AML1 negative, although some positive samples with negligible amounts of TEL-AML1 transcripts were still detected. INTERPRETATION AND CONCLUSIONS: This method has the sensitivity and reliability required to monitor the presence of minimal residual disease, and could be a powerful tool in monitoring the efficacy of the response to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Telomerase activity in thyroid fine needle aspirates.

OBJECTIVE: To study the utility of telomerase activity (TA) detection in thyroid fine needle aspirates (FNAs). STUDY DESIGN: One hundred two thyroid nodules were studied: 70 in FNA samples and 32 in frozen tumors. From among FNA samples, there were 57 nodules of the goiter, 1 adenoma, 7 papillary carcinomas, 1 medullary carcinoma and 1 lymphoma. Three cases of thyroiditis were excluded. The 32 frozen tissue tumors consisted of 5 follicular adenomas, 4 follicular carcinomas and 23 papillary carcinomas. TA was analyzed by Telomerase PCR ELISA (Roche Diagnostics, Indianapolis, Indiana, U.S.A.). RESULTS: TA was negative in the 57 nonneoplastic nodules and 6 follicular adenomas and positive in 3 of 4 follicular carcinomas and 10 of 30 papillary carcinomas. TA sensitivity was 41.4% and specificity 100%. Sensitivity for malignancy was higher (85.7%) in FNAs than in TA. CONCLUSION: TA seems highly specific for neoplasms of the thyroid. Further studies are needed to confirm whether TA detection could contribute to identifying neoplasms when FNAs are inconclusive for malignancy and in cases of scanty material.

Biomarkers, Tumor↗

PubMedDate not supplied

Comparative findings of lymphocytic thyroiditis and thyroid lymphoma.

OBJECTIVE: To compare the cytologic features of histologically proven lymphocytic (Hashimoto's) thyroiditis (Hashimoto's thyroitidis) and primary thyroid lymphomas (TL). STUDY DESIGN: Clinical histories, smears (stained with Diff-Quik, Papanicolaou stain or hematoxylin and eosin [HE]) and surgical specimens (HE slides) were reviewed in 25 cases of lymphocytic thyroiditis and 12 of thyroid lymphomas. RESULTS: Surgical specimens of thyroiditis were obtained for other medical reasons: goiter and compressive symptomatology in 21 cases and neoplasms in 4 (2 papillary carcinomas, 1 follicular carcinoma and 1 oncocytic adenoma). Seven cases were primary lymphomas, and 5 were secondary. Histologically there were 6 large B-cell lymphomas, 2 mantle cell lymphomas, 1 Burkitt lymphoma, 2 mucosal-associated lymphoid tissue lymphomas in blastic transformation and 1 of unknown type. Sensitivity for the diagnosis was 67.5% for HT and 92.3% for lymphoma. CONCLUSION: A heterogeneous population of small and large lymphocytes was the most frequent pattern in both diseases. The presence of a monotonous population of large lymphocytes or, more rarely, of small cells indicates a probable TL. Plasma cells favor HT. Other techniques are mandatory for the differentiation of cases with inconclusive diagnoses.

Adult↗