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Planta, Spain

Verdu M.,Histopat Laboratoris | Trias I.,Histopat Laboratoris | Roman R.,BIOPAT | Rodon N.,BIOPAT | And 2 more authors.
Revista Espanola de Patologia

Recently, the study of the EGFR mutations in lung cancer has become mandatory due to their usefulness in target therapy. Lately, the use of specific antibodies to study the most prevalent of these mutations has been introduced. The newly published discovery of the existence of a cross-reaction between the HER2 protein and the EGFR L858R-specific antibody in breast cancer led us to corroborate this cross-reactivity in other tumors; specifically, we have chosen gastric carcinomas where HER2 is routinely evaluated as a molecular therapy driver.Our series consists of 15 primary gastric carcinomas, 7 HER2 cases positive for overexpression/amplification and 8 negative cases for both techniques. EGFR L858R mutation was studied with immunohistochemistry and complemented with real time PCR when positive. Immunohistochemistry assay with EGFR L858R was positive in 5 of the HER2 positive carcinomas (71%), none of which was confirmed by PCR, and negative in all HER2 negative carcinomas. Conclusions: The EGFR L858R antibody gives false positive results in most gastric carcinomas with HER2 overexpression/amplification, confirming the results described previously in breast cancer. It is also important to bear in mind that HER2 has also been described in other carcinomas, including lung cancer. © 2014 SEAP y SEC. Source

Garcia-Pelaez B.,BIOPAT | Verdu M.,BIOPAT | Verdu M.,Histopat Laboratoris | Roman R.,BIOPAT | And 5 more authors.
Revista Espanola de Patologia

Sentinel lymph node assessment is an essential part of the staging procedure in breast cancer. Increasingly, One-Step Nucleic Acid Amplification (OSNA), an intraoperative molecular assay that measures the amount of cytokeratin 19 (CK19) mRNA present in the whole of the sentinel lymph node, is being used in the detection of sentinel lymph node metastasis, due to its superior sensitivity and equal specificity compared with conventional histological examination. CK19 positive immunostaining in a previous biopsy is recommended to avoid false negative results with OSNA analysis.The aim of our study was to assess the degree of CK19 positivity in series of breast carcinomas with particular emphasis on special histological subtypes. The total of 337 breast carcinomas studied were distributed in three series as follows: a retrospective unselected series studied on tissue microarray, a series of whole sections enriched for special histological subtypes and triple negative carcinomas, and a prospective series of biopsies studied in whole sections, prior to a routine OSNA assay.The results of our three series revealed that the great majority of breast carcinomas exhibits a diffuse CK19 positivity. Therefore it would be highly unlikely, especially in frequent variants, to have a false negative OSNA result due to lack of CK19 expression in the primary tumour. Heterogeneous expression was only observed in patients with infrequent variants (apocrine, adenoid cystic and medullary carcinomas) and/or TN profile. © 2014 SEAP y SEC. Source

High microsatellite instability (MSI-H) allows the identification of a subset of colorectal carcinomas associated with good prognosis and a higher incidence of Lynch syndrome. The aim of this work was to assess the interobserver variability and optimize our MSI-H prediction model previously published based on phenotypic features. The validation series collected from five different hospitals included 265 primary colorectal carcinomas from the same number of patients. The eight clinicopathological parameters that integrate our original model were evaluated in the corresponding centers. Homogeneity assessment revealed significant differences between hospitals in the estimation of the growth pattern, presence of Crohn-like reaction, percentage of cribriform structures, and Ki-67 positivity. Despite this observation, our model was globally able to predict MSI-H with a negative predictive value of 97.0%. The optimization studies were carried out with 615 cases and resulted in a new prediction model RERtest8, which includes the presence of tumor infiltrating lymphocytes at the expense of the percentage of cribriform structures. This refined model achieves a negative predictive value of 97.9% that is maintained even when the immunohistochemical parameters are left out, RERtest6. The high negative predictive value achieved by our models allows the reduction of the cases to be tested for MSI to less than 10%. Furthermore, the easy evaluation of the parameters included in the model renders it a useful tool for the routine practice and can reinforce other published models and the current clinical protocols to detect the subset of colorectal cancer patients bearing hereditary nonpolyposis colorectal cancers risk and/or MSI-H phenotype. © Springer-Verlag 2010. Source

Verdu M.,Histopat Laboratoris | Trias I.,Histopat Laboratoris | Roman R.,BIOPAT | Rodon N.,BIOPAT | And 6 more authors.
Applied Immunohistochemistry and Molecular Morphology

The coexpression of HER2 and EGFR L858R in a solitary nodule removed from the lung, whose mutation was not confirmed by molecular techniques, made us think about the possible existence of a cross-reaction between HER2 and the EGFR L858R-specific antibody. Our study was designed to further analyze the existence of this cross-reaction and stress the need to exclude a metastatic breast cancer when dealing with EGFR L858R-positive cases. The series consists of 42 primary breast carcinomas, 22 HER2 positive for overexpression and amplification, and 20 negative for both. EGFR mutations were studied by immunohistochemistry and confirmed using real-time PCR when positive. Immunohistochemistry assay with EGFR L858R was positive in 19 (86%) of the HER2-positive breast carcinomas and negative in all HER2-negative carcinomas. The EGFR L858R antibody gives false-positive results in most of the breast carcinomas with HER2 overexpression/amplification. As a consequence, it is essential to confirm any EGFR L858R-positive cases by molecular methods or at least discard the presence of HER2 overexpression/amplification before rendering a diagnosis. It is also important to consider that HER2 has been described in other carcinomas such as urothelial, gastric or ovarian, as well as lung, although infrequently. © Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. Source

Verdu M.,BIOPAT | Verdu M.,Histopat Laboratoris | Trias I.,BIOPAT | Trias I.,Histopat Laboratoris | And 8 more authors.
Virchows Archiv

ERG gene rearrangement has been identified as a highly specific alteration that is present in 40-50 % of prostate carcinomas. The standardization of an immunohistochemical assay with a novel anti-ERG antibody recently described would have significant diagnostic value. The aims of this study were to identify the incidence of this rearrangement in a Spanish population and to test the specificity of immunohistochemical ERG evaluation for prostate carcinomas. Three prostate tissue microarrays were constructed using radical prostatectomy specimens and related to grade, local invasion, and regional invasion. In addition to samples from malignant cases (160), specimens of prostatic hyperplasia (26) and high-grade prostatic intraepithelial neoplasia (10) were included. Tissue microarrays of 270 samples from most common malignant tumors (breast, colon, lung, and bladder) were also tested. All were analyzed by immunohistochemistry. Seventy-five out of 154 evaluable cases (49 %) of prostate carcinoma showed ERG expression; 52/75 showed strong staining. No ERG expression was observed in any of the high-grade prostatic intraepithelial neoplasia. ERG expression was independent of Gleason score (p = 0.160), extent of invasion (p = 0.517), and regional lymph node involvement (p = 0.816). No ERG expression was found in any other type of tumor, with the exception of one bladder cancer sample that showed focal and weak expression. The frequency of ERG detected in our study correlated with the results published for other Caucasian populations. Strong ERG protein expression was exclusively detected in prostate carcinomas, corroborating the specificity of ERG rearrangements for these tumors. Thus, detecting ERG using immunohistochemistry may be useful in routine practice in pathology departments. © 2013 Springer-Verlag Berlin Heidelberg. Source

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