Mitotic figure counts are overrated in resection specimen of invasive breast carcinoma

In order for some patients to benefit from aggressive chemotherapy for invasive breast carcinoma, many patients are currently being treated without little or no benefit. Enormous effort is hence being directed towards the identification of those patients who will need chemotherapy and those who will not. Since chemotherapy targets proliferating cells pathologists focus on the proliferative activity of tumors, as assessed by mitotic figure counts or by cell cycle specific immunohistochemical markers, such as Ki-67 and H3 histone. As far as the tumor grade is concerned, many of these studies have reported a tendency to up-grade carcinomas in resection specimen when compared to the initial diagnosis on the biopsy material, and most studies have noted that the upgrade in resection specimen is due solely or to a large extent to an increase in the mitotic figure count. In the present study, we propose a different explanation for the divergence in mitotic figure counts between biopsy and resection material. We assessed the proliferative activity of 52 invasive ductal carcinomas and confirm that the number of mitotic figures significantly increased by a factor of more than 3 in resection specimen over the biopsy material, while at the same time the pan-cell cycle specific marker MIB-1 yieldes comparable results. we propose that the delayed formalin fixation of resection specimen allows cell cycle activities to continue for a long time, up to many hours, and that this leads to an arrest of mitoses in metaphase where they are readily identified by the pathologist. We propose that the mitotic figure count in the rapidly fixed biopsy cores better represent the tumor biology and should be used as a basis for chemotherapy therapeutic decisions.

Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling.

It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through upregulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix-remodeling enzymes. In human skin samples, stromal fields adjacent to multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer.

Transplantation of a human mammary carcinoma cell line (BT 20) into nude mice.

Cell suspensions of a human mammary carcinoma cellline (BT 20), wh en injected subcutaneously into nude athymie mice (BALB/c NujNu), produced tumor nodules at the injection site. Subsequent seriai transM plantations also gave rise to neoplastic nodules after latency periods averaging 3 weeks. The nodules displayed morphologie and functional characteristics comparable to those of the original tumor cells. Metastases, however, were not observed in any of the tumor-bearing mice.

Biodistribution of anti-CEA F(ab')2 fragments after intra-arterial and intravenous injection in patients with liver metastases due to colorectal carcinoma.

The biodistribution of simultaneous intra-arterial and intravenous injections of a radiolabelled anti-CEA MAb F(ab')2 fragment was studied in three patients with liver metastases from colorectal cancer. Identical MAb fragments, labelled with either 125I or 131I, were injected over a period of 30 min into the hepatic artery and into a peripheral vein. After 1 or 2 days, biodistribution was measured in the surgically removed metastases, normal tissue samples and blood. By tissue radioactivity counting, tumour uptake in the range 6.3-9.1% of injected dose per gram was found. Superimposable metastasis-to-blood and metastasis-to-normal liver ratios were obtained for both iodine isotopes in all three patients. The results indicate that the intra-arterial injection of MAb F(ab')2 fragments gives no measurable advantage over more convenient injections into a peripheral vein.

Rôle de l'EGFR dans le cancer pulmonaire non à petites cellules [The role of EGFR in non-small cell lung carcinoma]

EGFR receptor is expressed on most of the non small cell lung carcinoma (NSCLC) cells. Its relative importance in oncogenesis and tumour progression seems to greatly vary among NSCLC. Two molecules targeting differently EGFR are currently used for the treatment of metastatic NSCLC. cetuximab, a monoclonal antibody directed against the extracellular domain of the receptor, leads to a moderate survival benefit when associated with standard first-line chemotherapy. Erlotinib, a small EGFR tyrosine-kinase inhibitor molecule is used in 2nd or 3rd treatment line. Predictive factors for efficiency of these new treatments are subjects of intense research, in order to allow a better selection of the patients who could benefit from such a strategy.

Prise en charge du carcinome hépatocettulaire en 2010 [Management of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.

Dermatofibrosarcoma presenting as a nodule in the breast of a 75-year-old woman: a case report.

ABSTRACT: INTRODUCTION: Dermatofibrosarcoma protuberans is a rare neoplasm of soft tissues and its location in the breast is extremely uncommon. Confusion is possible with other primary breast lesions. CASE PRESENTATION: A 75-year-old Caucasian woman presented with a mass in her left breast 21 years after being diagnosed with invasive ductal carcinoma of the right breast, treated by a right mastectomy and axillary dissection followed by radiotherapy and breast reconstruction. Mammography revealed a dish-shaped skin nodule formation in the upper outer quadrant of her left breast. Echography confirmed the presence of a lesion measuring 1.4 x 0.8 cm. Based on imaging, the diagnosis was a probable angiosarcoma. Due to the presence of a pacemaker for cardiac arrhythmia and full anticoagulation therapy for a pulmonary embolism, magnetic resonance imaging and a biopsy were not done. We proceeded directly to a quadrantectomy and the final diagnosis revealed a dermatofibrosarcoma protuberans, 1. 8 cm in its greatest microscopic dimension, located 0.1 cm from the upper surgical margin. To ensure the wide resection margins required for this type of neoplasm, a re-excision was performed. CONCLUSION: A dermatofibrosarcoma protuberans of the breast is an uncommon discovery. The aim of this case report is to highlight the importance of the surgical procedure in cases of the discovery of dermatofibrosarcoma protuberans. Re-excision may be necessary to ensure adequate resection margins.

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.

Management of adenoid cystic carcinoma of the breast: a Rare Cancer Network study.

BACKGROUND: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC.¦METHODS: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy).¦RESULTS: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT.¦CONCLUSION: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.

Carcinomes épidermoïdes de l'hypopharynx et du larynx : prise en charge fondée sur les preuves Squamous cell carcinoma of the hypopharynx and larynx: evidence-based care.

Les carcinomes épidermoïdes de l'hypopharynx et du larynx peuvent être traités par chirurgie et/ou radiothérapie en fonction de la taille tumorale. Pour les petites tumeurs, les résultats sont équivalents. Pour les tumeurs localement avancées, l'approche chirurgicale est mutilante et nécessite une (pharyngo)laryngectomie totale. La chimioradiothérapie exclusive a montré tout son intérêt mais au prix de séquelles tardives. Dans le but de diminuer ces séquelles et les mutilations, la chimiothérapie d'induction par cisplatine, docétaxel et 5FU à visée de préservation d'organe devient le standard de traitement mais il manque des études solides de comparaison de cette approche avec la chimioradiothérapie exclusive. Il n'est pas possible de conclure quant à la supériorité d'un schéma en survie globale. Quand la chimiothérapie d'induction est choisie, les modalités de potentialisation éventuelle de la radiothérapie ne sont pas établies. Squamous cell carcinomas of larynx and hypopharynx can be treated by surgery and/or radiotherapy according to tumor size. For small tumors, the results are similar. For locally advanced tumors, the surgical approach is mutilating and requires a total (pharyngo)laryngectomy. Exclusive chemoradiotherapy has shown its interest at the cost of late sequelae. In order to reduce these effects and mutilation, induction chemotherapy with cisplatin, docetaxel and 5FU for organ preservation becomes the standard treatment but there are no solid studies comparing this approach with the exclusive chemoradiotherapy. And it is not possible to conclude as to the superiority of a scheme in terms of overall survival. When chemotherapy is chosen, the modalities of any potentiation of radiation have not been yet established.

Merkel cells and the individuality of friction ridge skin

There is no definite theory yet for the mechanism by which the pattern of epidermal ridges on fingers, palms and soles forming friction ridge skin (FRS) patterns is created. For a long time growth forces in the embryonal epidermis have been believed to be involved in FRS formation. More recent evidence suggests that Merkel cells play an important part in this process as well. Here we suggest a model for the formation of FRS patterns that links Merkel cells to the epidermal stress distribution. The Merkel cells are modeled as agents in an agent based model that move anisotropically where the anisotropy is created by the epidermal stress tensor. As a result ridge patterns are created with pattern defects as they occur in real FRS patterns. As a consequence we suggest why the topology of FRS patterns is indeed unique as the arrangement of pattern defects is sensitive to the initial configuration of Merkel cells.

Antagonistic effect of the inflammasome on thymic stromal lymphopoietin expression in the skin.

BACKGROUND: Innate immune sensors control key cytokines that regulate T-cell priming and T-cell fate. This is particularly evident in allergic reactions, which represent ideal systems to study the interplay of innate and adaptive immunity. In patients with contact dermatitis, inflammasome-mediated IL-1 activation is responsible for a TH1 immune response. Surprisingly, the IL-1 signaling pathway was also proposed to control the activation of thymic stromal lymphopoietin (TSLP), a cytokine implicated in development of the TH2 response in patients with atopic dermatitis (AD) and asthma. OBJECTIVES: We sought to assess the effect of the inflammasome on TSLP expression levels and the development of AD. METHODS: We studied the effect of the inflammasome activator 2,4-dinitrofluorobenzene, and IL-1β on TSLP mRNA expression levels in mouse and human cell lines (in vitro assays), as well as in live mice and on human skin transplants. We also assessed the effect of 2,4-dinitrofluorobenzene on TSLP and the TH2 response in mice in which the inflammasome and IL-1 signaling pathways were blocked, either genetically or pharmacologically, in 2 models of AD. RESULTS: We provide in vitro and in vivo evidence that inflammasome activation has an inhibitory role on TSLP mRNA expression and TH2 cell fate in the skin. We also show that solvents influence the activation of TSLP and IL-1β and direct the T-cell fate to a given hapten. CONCLUSION: Our observations strongly suggest that the TH1 versus TH2 cell fate decision is regulated at multiple levels and starts with innate immune events occurring within peripheral epithelial tissues.

Role of the serine protease CAP1/Prss8 and its inhibitor in the skin

The skin is the largest organ of the human body and protects it from water loss and mechanical damage. This barrier function is mainly provided by the epidermis, the outermost layer of the skin. This balance is regulated by several factors, including serine proteases, serine protease inhibitors and protease target substrates, such as receptors. Any mutations or alterations in the expression of these factors can lead to skin diseases. One of the players in this skin balance is the serine protease CAP1/Prss8, whose over-expression causes ichthyosis, hyperplasia and inflammation. This phenotype can be completely restored in the absence of PAR2 (protease-activated receptor 2) (Frateschi et al., 2011). During my thesis, I demonstrated that CAP1/Prss8 induces skin disease even if its catalytic triad is mutated. Additionally, I demonstrated an inhibitory effect of the serine protease-inhibitor nexin-1 (also called serpinE2, PN-1) on CAP1/Prss8, since nexin-1 negated the effects of both catalytically active and inactive CAP1/Prss8 over-expression. Indeed, CAP1/Prss8 and nexin-1 interact in vitro, but independent of the catalytic triad of CAP1/Prss8. These results demonstrate a novel mechanism of interaction between CAP1/Prss8 and nexin-1, and indicate that the catalytic triad of CAP1/Prss8 is dispensable for nexin-1 inhibition and PAR2 activation. These observations in vivo and in vitro could be helpful to specifically target drugs to treat ichthyoses-like skin diseases, like e.g. atopic dermatitis. - La peau est l'un des organes les plus importants du corps humain au regard de sa surface et de sa masse. Ses principales fonctions sont de nous protéger contre l'entrée de pathogènes et de former une barrière imperméable qui empêche la déshydratation. Ces fonctions sont principalement assurées par l'épiderme, la couche la plus superficielle de la peau, et garanties par plusieurs "acteurs", comme par exemple les sérine-protéases, les inhibiteurs de sérine- protéases ou les protéases cibles comme les récepteurs. Toute mutation ou altération de l'un de ces "acteurs" peut aboutir au déclanchement de maladies de la peau. Pour mieux comprendre les conséquences biologiques résultant d'une altération d'expression de CAP1/Prss8, une serine-protéase normalement exprimée au niveau de l'épiderme, nous avons généré des souris transgéniques surexprimant CAP1/Prss8 au niveau de la peau. Ces dernières présentent une peau squameuse, un épiderme hypertrophique, des processus inflammatoires et des prurits conséquents. Ces symptômes disparaissent si le gène du récepteur PAR2, qui régule l'activité des cellules de l'épiderme, est inactivé. Dans le but de vérifier si le phénotype observé chez les souris CAP1/Prss8 résulte de l'action du site catalytique de CAP1/Prss8, nous avons généré des souris CAP1/Prss8 chez lesquelles nous avons muté les trois acides aminés du site catalytique en alanine. Etonnement ces souris ont développé les mêmes problèmes de peau que les souris CAP1/Prss8, démontrant que l'effet de CAP1/Prss8, dans ce modèle animal, n'est pas lié à son site catalytique. Nous avons également montré in vivo, que la sérine-protéase nexin-1 (aussi appelée SERPINE2, PN-1) est capable d'exercer un effet inhibiteur sur CAP1/Prss8 indépendamment de l'activité du site catalytique de CAP1/Prss8. De plus, nous avons remarqué in vitro que CAP1/Prss8 et nexin-1 interagissent bien que la triade catalytique de CAP1/Prss8 soit enzymatiquement inactivée. Ces observations, in vivo et in vitro, pourraient être utilisées dans l'élaboration de médicaments contenant nexin-1, pour le traitement de pathologies de la peau telles l'ichthyose et la dermatite atopique.

Role of the epithelial sodium channel (ENaC) in the epidermal barrier function of the skin

Abstract In humans, the skin is the largest organ of the body, covering up to 2m2 and weighing up to 4kg in an average adult. Its function is to preserve the body from external insults and also to retain water inside. This barrier function termed epidermal permeability barrier (EPB) is localized in the functional part of the skin: the epidermis. For this, evolution has built a complex structure of cells and lipids sealing the surface, the stratum corneum. The formation of this structure is finely tuned since it is not only formed once at birth, but renewed all life long. This active process gives a high plasticity and reactivity to skin, but also leads to various pathologies. ENaC is a sodium channel extensively studied in organs like kidney and lung due to its importance in regulating sodium homeostasis and fluid volume. It is composed of three subunits α, ß and r which are forming sodium selective channel through the cell membrane. Its presence in the skin has been demonstrated, but little is known about its physiological role. Previous work has shown that αENaC knockout mice displayed an abnormal epidermis, suggesting a role in differentiation processes that might be implicated in the EPB. The principal aim of this thesis has been to study the consequences for EPB function in mice deficient for αENaC by molecular and physiological means and to investigate the underlying molecular mechanisms. Here, the barrier function of αENaC knockout pups is impaired. Apparently not immediately after birth (permeability test) but 24h later, when evident water loss differences appeared compared to wildtypes. Neither the structural proteins of the epithelium nor the tights junctions showed any obvious alterations. In contrary, stratum corneum lipid disorders are most likely responsible for the barrier defect, accompanied by an impairment of skin surface acidification. To analyze in details this EPB defect, several hypotheses have been proposed: reduced sensibility to calcium which is the key activator far epidermal formation, or modification of ENaC-mediated ion fluxes/currents inside the epidermis. The cellular localization of ENaC and the action in the skin of CAPl, a positive regulator of ENaC, have been also studied in details. In summary, this study clearly demonstrates that ENaC is a key player in the EPB maintenance, because αENaC knockout pups are not able to adapt to the new environment (ex utero) as efficiently as the wildtypes, most likely due to impaired of sodium handling inside the epidermis. Résumé Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses pathologies. ENaC est un canal sodique très étudié dans le rein et le poumon pour son importance dans la régulation de l'homéostasie sodique et la régulation du volume du milieu intérieur. Il est composé de 3 sous unités, α, ß et y qui forment un pore sélectif pour le sodium dans les membranes. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris dont le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la différentiation et pourrait même être impliqué dans la barrière épithéliale. Le but de cette thèse fut l'étude de la barrière dans ces souris knockouts avec des méthodes moléculaires et physiologiques et la caractérisation des mécanismes moléculaire impliqués. Dans ce travail, il a été montré que les souris mutantes présentaient un défaut de la barrière. Ce défaut n'est pas visible immédiatement à la naissance (test de perméabilité), mais 24h plus tard, lorsque les tests de perte d'eau transépithéliale montrent une différence évidente avec les animaux contrôles. Ni les protéines de structures ni les jonctions serrées de l'épiderme ne présentaient d'imperfections majeures. A l'inverse, les lipides de la couche cornée présentaient un problème de maturation (expliquant le phénotype de la barrière), certainement consécutif au défaut d'acidification à la surface de la peau que nous avons observé. D'autres mécanismes ont été explorées afin d'investiguer cette anomalie de la barrière, comme la réduction de sensibilité au calcium qui est le principal activateur de la formation de l'épiderme, ou la modification des flux d'ions entre les couches de l'épiderme. La localisation cellulaire d'ENaC, et l'action de son activateur CAPl ont également été étudiés en détails. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des knockouts ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme. Résumé tout public Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses maladies. ENaC est une protéine formant un canal qui permet le passage sélectif de l'ion sodium à travers la paroi des cellules. Il est très étudié dans le rein pour son importance dans la récupération du sel lors de la concentration de l'urine. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris où le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la peau et plus particulièrement la fonction de barrière de l'épiderme. Le but de cette thèse fut l'étude de la fonction de barrière dans ces souris mutantes, au niveau tissulaire et cellulaire. Dans ce travail, il a été montré que les souris mutantes présentaient une peau plus perméable que celle des animaux contrôles, grâce à une machine mesurant la perte d'eau à travers la peau. Ce défaut n'est visible que 24h après la naissance, mais nous avons pu montrer que les animaux mutants perdaient quasiment 2 fois plus d'eau que les contrôles. Au niveau moléculaire, nous avons pu montrer que ce défaut provenait d'un problème de maturation des lipides qui composent la barrière de la peau. Cette maturation est incomplète vraisemblablement à cause d'un défaut de mouvement des ions dans les couches les plus superficielles de l'épiderme, et cela à cause de l'absence du canal ENaC. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des mutants ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme.