NRAS Q61R , BRAF V600E immunohistochemistry: a concomitant tool for mutation screening in melanomas

International audienceThe determination of NRAS and BRAF mutation status is a major requirement in the treatment of patients with metastatic melanoma. Mutation specific antibodies against NRAS(Q61R) and BRAF(V600E) proteins could offer additional data on tumor heterogeneity. The specificity and sensitivity of NRAS(Q61R) immunohistochemistry have recently been reported excellent. We aimed to determine the utility of immunohistochemistry using SP174 anti-NRAS(Q61R) and VE1 anti-BRAF(V600E) antibodies in the theranostic mutation screening of melanomas. 142 formalin-fixed paraffin-embedded melanoma samples from 79 patients were analyzed using pyrosequencing and immunohistochemistry. 23 and 26 patients were concluded to have a NRAS-mutated or a BRAF-mutated melanoma respectively. The 23 NRAS (Q61R) and 23 BRAF (V600E) -mutant samples with pyrosequencing were all positive in immunohistochemistry with SP174 antibody and VE1 antibody respectively, without any false negative. Proportions and intensities of staining were varied. Other NRAS (Q61L) , NRAS (Q61K) , BRAF (V600K) and BRAF (V600R) mutants were negative in immunohistochemistry. 6 single cases were immunostained but identified as wild-type using pyrosequencing (1 with SP174 and 5 with VE1). 4/38 patients with multiple samples presented molecular discordant data. Technical limitations are discussed to explain those discrepancies. Anyway we could not rule out real tumor heterogeneity. In our study, we showed that combining immunohistochemistry analysis targeting NRAS(Q61R) and BRAF(V600E) proteins with molecular analysis was a reliable theranostic tool to face challenging samples of melanoma

HLA-DR expression in melanoma: from misleading therapeutic target to potential immunotherapy biomarker

Since the advent of anti-PD1 immune checkpoint inhibitor (ICI) immunotherapy, cutaneous melanoma has undergone a true revolution with prolonged survival, as available 5-year updates for progression-free survival and overall survival demonstrate a durable clinical benefit for melanoma patients receiving ICI. However, almost half of patients fail to respond to treatment, or relapse sooner or later after the initial response to therapy. Little is known about the reasons for these failures. The identification of biomarkers seems necessary to better understand this resistance. Among these biomarkers, HLA-DR, a component of MHC II and abnormally expressed in certain tumor types including melanoma for unknown reasons, seems to be an interesting marker. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on the potential interest of HLA-DR expression in melanoma as a predictive biomarker of ICI outcome

Reconsidering the Turnaround Times for BRAF V600 Mutation Analysis in Non-Small-Cell Lung Cancer: A Molecular Diagnosis in One Day Is Achievable for Rapid Treatment Choices

As reported by Auliac et al., patients with BRAF-mutated non-small-cell lung cancer (NSCLC) have particular clinicopathologic features and prognosis. [...

MET Immunohistochemistry Should Be Avoided in Selecting Non–small-cell Lung Cancers Requiring MET Exon 14 Skipping Mutation Analysis

International audienc

Bilan des lésions foetales et placentaires rencontrées au cours de l'exposition à l'alcool in utero

Les effets de l'alcoolisation maternelle sur le foetus sont un véritable problème de santé publique. Leur prévention passe par une identification des patientes à risque de consommation excessive, ce dépistage difficile, avant tout clinique, pouvant s'aider de paramètres biologiques mais aussi des apports de l'anatomie pathologique en terme d'examen placentaire et parfois foetopathologique. Cette étude basée sur 67 examens placentaires et 15 examens foetaux décrit les lésions placentaires parfois évocatrices d'un tableau d'exposition foetal à l'alcool et les différents syndromes liés à l'alcoolisation foetale dont le syndrome d'alcoolisation foetale et les anomalies congénitales liées à l'alcool sont des diagnostic possible en foetopathologie dès les premières semaines de la vie, selon des critères proches de ceux utilisés en pédiatrie. En dehors d'une synthèse concernant la tératogénicité de l'alcool sur un plan descriptif mais aussi physiopathologique, cette étude conclut sur la nécessité de diagnostiquer ce trouble addictif maternel afin d'assurer un prise en charge adaptée du couple mère-enfant et de prévenir les récidives d'une pathologie fréquente, grave, souvent méconnue et pourtant curable.BREST-BU Médecine-Odontologie (290192102) / SudocSudocFranceF

Decalcification can cause the failure of BRAF molecular analyses and anti‐BRAFV600E VE1 immunohistochemistry

International audienceBRAF mutation detection is worthwhile for the management of patients with some advanced cancers. The tumor samples are sometimes difficult to analyze using DNA-based molecular methods because of poor tumor DNA quality or quantity. Anti-BRAFV600E VE1 immunohistochemistry (IHC) has been proposed as a valuable ancillary tool to analyze some "molecularly challenging" tumor samples. In this technical study, we focused on its application in the field of decalcified tumor samples. We selected four patients with known BRAFV600E-mutated cancer (3 metastatic melanomas and 1 hairy cell leukemia) and paired non-decalcified/decalcified tumor samples. Molecular analyses failed in the four decalcified samples (3 bone metastases and 1 osteo-medullar biopsy) with non-contributive mutation status. Whereas non-decalcified tumor samples were all positive using anti-BRAFV600E VE1 IHC, the four decalcified samples were concluded negative. Because decalcified tumor samples are difficult to analyze from a molecular point of view, it is tempting to use IHC instead of DNA-based methods searching for BRAFV600E mutations in these samples. Nevertheless, the decalcification process may also cause false-negative results using VE1 IHC. Decalcified samples require specific and optimized IHC and molecular protocols and quality controls

The Histopathological “Placentitis Triad” Is Specific for SARS-CoV-2 Infection, and Its Acute Presentation Can Be Associated with Poor Fetal Outcome

(1) Background: Placental histological lesions reported in relation with SARS-CoV-2 infection are various, with potential consequences such as fetal growth retardation, prematurity or stillbirth/neonatal death. We report here on a placental pathological association which could be specific for SARS-CoV-2 infection and associated with poor fetal outcome; (2) Methods: We collected all the placental pathological examinations performed in Brest University Hospital (France) since the beginning of COVID-19 pandemic with a known maternal SARS-CoV-2 infection and a poor pregnancy outcome. In these cases, we described the pathological lesions and we searched for these lesions in a large series of placentas collected and examined in the same institution before the SARS-CoV-2 pandemic; (3) Results: Three cases with severe fetal outcome (tardive abortion, prematurity, neonatal death), from the first to the third trimesters of pregnancy, were included. The three cases showed features of massive and acute “placentitis triad” consisting in massive perivillous fibrin deposition, sub-acute intervillositis and trophoblastic necrosis. This association was not encountered in any of 8857 placentas analyzed during the period between 2002 and 2012 in our institution; (4) Conclusions: The “placentitis triad” appears to be specific for SARS-CoV-2 infection and, in case of massive and acute presentation, could result in poor fetal outcome

About concomitant KRAS and other molecular alterations in non–small cell lung cancers

International audienc