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PubMedDate not supplied

[Laboratory variables and stratification of small-cell lung cancer patients: recommendations for therapeutic trials and for clinical practice guidelines].

OBJECTIVE: To identify, through a systematic review of the literature, the laboratory variables that, in addition to performance status and to extent of the disease, would allow a more accurate stratification of small-cell lung cancer patients who participate in chemotherapy trials, with or without radiotherapy. Secondary aim: to compare the results of our systematic review with the recommendations made in current clinical practice guidelines. METHODS: Update of two recently published systematic reviews, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1143 publications retrieved, exclusion and inclusion criteria allow us to include 13 studies in our review. The three variables which were the most often found significant in multivariate statistical analysis, were: pre-therapeutic levels of laboratory variables (13/13), performance status (12/13), and degree of tumour invasion (10/10). Among the laboratory variables, serum lactate dehydrogenase (LDH) is the only one that was quite consistently found to be of independent prognostic significance, with p values or hazard ratios quite close to those obtained with performance status, or with extent of the disease. The recommendations made in the four clinical practice guidelines that we retrieved, are often vague regarding laboratory variables, and sometimes they even contradict each others. CONCLUSIONS: Available evidence would support the recommendation that pretreatment LDH should be systematically measured in order to stratify patients in therapeutic trials. If other laboratory variables were to be measured in addition to LDH for this purpose, it seems that alkaline phosphatase (ALP), and to a lesser extent, sodium and white blood cell counts, might be the best suited ones. Nevertheless, further studies are necessary to more clearly support this latter recommendation. Available evidence would not support the measurement of any other laboratory variable in this context, before, during, or after treatment. Our recommendations are more in agreement with the recommendations made in the clinical practice guidelines that use evidence-based methods than with the guidelines that do not.

Carcinoma, Small Cell↗
PubMed2004

Derivation and validation of a risk stratification model to identify coronary artery disease in women who present to the emergency department with potential acute coronary syndromes.

OBJECTIVES: To derive and validate a model to identify women who would benefit from further evaluation of chest pain after an initial negative emergency department (ED) evaluation for acute coronary syndrome (ACS). METHODS: The derivation and validation cohorts were comprised of women who presented to the ED with chest pain at two university hospitals. Patients were excluded if the initial electrocardiogram (ECG) or cardiac markers were consistent with ACS. Patients were followed for 30 days after the index visit to identify evidence of coronary artery disease (CAD), which was defined as a positive diagnostic study, myocardial infarction, or death. The authors performed a logistic regression analysis to identify significant predictors of CAD. A scoring system was developed based on the B-coefficient of these significant predictors. Levels of risk were assigned by summing and categorizing the cumulative risk score into low-, moderate-, and high-risk groups. RESULTS: The derivation and validation sets were comprised of 733 and 2,440 women, respectively. From the derivation set predictors of CAD (score) were history of CAD (1), age > or = 60 years (1), and high clinical suspicion (3). Low risk was defined as a score = 0, moderate risk score = 1-2, high risk score > or = 3. In the validation set, the numbers of patients with evidence of CAD were four of 1,348 (0.30%), 18 of 498 (3.6%), and 71 of 594 (11.9%) in the low-, moderate-, and high-risk groups, respectively. CONCLUSIONS: The risk of underlying CAD in women who present to the ED with potential ACS may be determined using a simple risk stratification score.

California↗
PubMed2004

[Invasive angiography, computed tomography or magnetic resonance imaging for coronary imaging and cardiovascular risk stratification? Regulatory and practical considerations].

In 2003, risk stratification in coronary heart disease is routinely performed by the results of coronary angiogram, the invasive gold standard angiography. Combined with the left ventricular ejection fraction assessment, the classification in one, two or three vessel disease remain the cornerstone of the revascularization strategy despite well-known limitations of this approach. Invasive coronary angiography is a mature technic with recommendations for training program and guidelines for indications. By comparison, the new noninvasive coronary imaging tools, computed tomography (CT) and magnetic resonance (MR) imaging, are just emerging. Coronary artery MR angiography is one of the most challenging areas because of the size and topology of the coronary arteries, as well as cardiac and respiratory motion. Multidetector-row and multisclice spiral computed tomography appear of most value for the detection of coronary artery disease with an excellent negative predictive value for proximal and middle main branches. Together, MR and CT, provide unique information that may predict cardiovascular risk. They identify flow-limiting coronary stenoses and calcified plaques, directly image the atherosclerotic lesions, measure atherosclerotic burden and characterize plaque components. Nevertheless, invasive coronary angiography still remain the first step of percutaneous coronary intervention. Therefore, one of the ultimate goals for the clinicians is the identification of the high-risk patient through a combination of strategies such as assessment of conventional risk factors, blood markers, and imaging. Indifferently to the imaging tool, the treatment should consider a human being and not only a picture.

Contraindications↗
PubMed2004

[Risk stratification and prevention of sudden death in patients with heart failure].

Patients with heart failure can die of progressive refractory heart failure or sudden cardiac death. This article reviews the major clinical predictors of sudden death in patients with heart failure due to left ventricular systolic dysfunction. Although earlier studies have identified many independent univariate predictors of reduced survival in these patients, the positive predictive value of most of them is low. Cardioverter defibrillator implantation has been shown to be the most effective therapy in patients resuscitated after cardiac arrest caused by ventricular fibrillation or poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction, low New York Heart Association functional class, unsustained ventricular tachycardia and inducibility of ventricular arrhythmia in electrophysiological studies may also identify high-risk patients who are candidates for cardioverter defibrillator implantation. The role of amiodarone in preventing sudden death in high-risk patients with heart failure seems to be small. Further studies are needed to improve risk stratification criteria to select patients with heart failure who are candidates for cardioverter defibrillator implantation.

Clinical Trials as Topic↗
PubMed2004

[Stratification of free air space and its dynamics in the process of co-composting].

Co-composting of sewage sludge and pig manure was studied. Free air space (FAS) in the whole composting pile was 26.2% at the temperature rising stage and 42.3% at the stage of high temperature composting. FAS in the upper portion of composting pile was higher than that in the lower, where the air was enough for microorganism to live on for two stages above. The FAS was 52.4% at the stage of the cooling, when the effect of stratification of FAS was significant. The FAS in the upper pile was bigger than that in the middle, which was bigger than that in the lower. At the stageof maturing, FAS was 54.7% and its stratified effect weakened, but the capability of aeration in the upper and in the middle of the pile was larger than that in the lower. At the different stages of composting, the degree of difference of FAS was of the order: the cooling stage > the high temperature stage > maturing stage > the temperature rising stage. The difference in the pile for every stage of composting was as follows: the upper > the middle > the lower. The change of FAS agreed with two-order kinetics.

Animals↗
PubMed2005

[Acute coronary syndromes without persistent ST-segment elevation: is risk stratification correctly applied?].

Risk stratification of patients with acute coronary syndromes is of paramount importance in achieving maximal benefit from current therapeutic modalities and for correct resource allocation. Since risk prediction based on the integration of key prognostic variables is relatively inaccurate, the clinical guidelines of the European Society of Cardiology (which have been endorsed by the Italian Federation of Cardiology) suggest an univariate approach favoring the sensitivity of the detection of high-risk patients compromising specificity. Such an approach is likely to identify a large population of high-risk patients possibly causing a mismatch between the number of patients in need of invasive evaluation and treatment, and the availability of interventional resources. Most of the risk of adverse cardiac events can be captured by the observation of three prognostic indicators: the presence of heart failure, the finding of ST-segment shifts (both elevation or depression) in the presenting electrocardiogram, and the elevation of markers of myocardial damage. The risk can be even higher in subjects who concurrently display additional risk features such as diabetes, renal insufficiency, advanced age, or previous revascularization procedures. Such patients are likely to be less treated both medically and invasively, than patients without such characteristics. The results of Italian regional registries show a favorable temporal trend toward a more a aggressive approach in such neglected high-risk subgroups.

Acute Disease↗
PubMed2005

Cardiac risk stratification in patients with congestive heart failure: a catecholamines-beta-adrenoceptor-cAMP pathway.

OBJECTIVE: To investigate the stratification risk of catecholamines-beta-adrenoceptor (beta-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF). METHODS: A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE) and epinephrine (E), lymphocytes beta-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered. RESULTS: The period between the initial entry and the last follow-up measurement were 51 +/- 16 months, the total duration of clinical follow-up after the last measurement were 14 +/- 8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above 3.5 nmol/L, and the intralymphocyte cAMP content above 3.5 pmd x mg(-1) x pro(-1) from baseline to follow-up were significant adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the patients with the intralymphocyte cAMP content below and above 3.5 pmd x mg(-1) x pro(-1) (HR: 2.79; 95% CI: 1.04-6.83; P = 0.017), but difference was not significant between the beta-AR density below and above median. CONCLUSIONS: Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.

Aged↗
PubMed2005

Risk stratification and prognosis of patients with known or suspected coronary artery disease by use of supine bicycle exercise stress echocardiography.

BACKGROUND: The aim of this study was to assess the long-term predictive values of supine bicycle exercise stress echocardiography (ESE), and the ESE additional role compared to other traditional clinical and rest echocardiographic variables, in 607 patients with low, intermediate and high pretest risk of cardiac events. METHODS: Clinical status and long-term outcome were assessed for a mean period of 46 months (range 12-60 months). ESE was performed for the diagnosis of suspected coronary artery disease (CAD) in 267 patients (43.9%), and for risk stratification of known CAD in 340 patients (56.1%). At baseline, the mean value of wall motion score index (WMSI) was 1.22 +/- 0.36, and the mean left ventricular ejection fraction was 58.5 +/- 10.9%. RESULTS: ESE was positive for ischemia in 210 patients (34.9%), while ECG was suggestive for ischemia in 157 patients (25.8%). During the test only 97 patients (15.9%) experienced angina. At peak effort, the mean WMSI was 1.38 +/- 0.46. A low workload was achieved by 158 patients (26.1%). During the follow-up period there were 222 events, including 82 hard events (36.9%), 48 deaths (21.6%) and 34 acute non-fatal myocardial infarction (15.3%). At stepwise multivariate model, cigarette smoking (p < 0.01), peak WMSI (p < 0.001), ESE positive for ischemia (p < 0.001) and low workload (p < 0.01) were the only independent predictors of cardiac death, while positive ESE, peak WMSI, angina during the test and hypercholesterolemia were the only independent determinants of hard cardiac events. The cumulative 5-year mean survival rate according to ESE response was 95.9% in patients with negative ESE, and 83.7% in patients with positive ESE (log rank 13.6; p < 0.00001). CONCLUSIONS: ESE yields prognostic information in known or suspected CAD, especially in patients with intermediate pretest risk level. The combined evaluation of clinical variables and other ESE variables, such as peak WMSI and exercise capacity, may further select patients at greatest risk of cardiac death in the overall population.

Coronary Artery Disease↗
PubMed2005

Immunohistochemical staining for cyclin D1 and Ki-67 aids in the stratification of atypical ductal hyperplasia diagnosed on breast core biopsy.

A diagnosis of atypical ductal hyperplasia (ADH) after breast core biopsy usually is followed by an excisional biopsy to exclude the presence of a more significant lesion. To determine whether the immunohistochemical expression of cyclin D1 (CyD1) and Ki-67 can aid in case stratification for the likelihood of finding ductal carcinoma in situ (DCIS) on subsequent excision, we immunohistochemically stained 21 consecutive ADH cases diagnosed by core biopsy, and proliferation indices (PIs) were calculated for each case. Fluorescence in situ hybridization to detect CCND1 amplification was performed in 10 cases. In 5 cases, DCIS (with or without invasive carcinoma) was identified in the subsequent excision. The mean PICyD1 and PIKi-67 for these cases were significantly higher than in the remainder (P = .03 and P = .05, respectively). The sensitivities of PICyD1 and PIKi-67 for the presence of DCIS on subsequent excision were 100%, and the specificities were 75% and 69%, respectively. The specificity of the 2 markers combined was 88%. The number of cells with CCND1 amplification was higher in cases with DCIS or ADH on subsequent excision. Immunostaining for CyD1 and Ki-67 might help stratify cases of ADH on core biopsy and identify patients unlikely to have DCIS found on excision.

Aged↗
PubMed2006

Oxidative stress assays for disease risk stratification.

Despite the fact that oxidative stress is a significant aetiological factor in several degenerative diseases, its measurement is rarely a part of "routine analyses" performed in hospital clinical chemistry laboratories. This situation is likely to change, as interest in this topic is increasing rapidly. Here we review the pertinent literature, with an assessment of assays for oxidative stress, and categorize them under: (i) assays for monitoring lipid peroxidation, (ii) assays for measuring oxidized amino acids, (iii) assays for measuring oxidized nucleic acids, (iv) assays based on physicochemical and immunological properties of oxidized low-density lipoprotein, and (v) assays for measuring the antioxidant capacity of body fluids and tissues. Our overview should be of help when choosing appropriate laboratory assays for oxidative stress and for routine disease risk stratification.

Amino Acids↗
PubMed2006

[Risk stratification in non-ST segment elevation myocardial infarction].

Patients with either unstable angina or non ST elevation myocardial infarction are usually submitted to the emergency department with similar symptoms and signs. Generally cardiac enzyme determinations can differentiate these two conditions. Elevation of these enzymes and their detection in blood stream takes a certain amount of time. A number of studies demonstrated lately that the high risk patients benefit more aggressive treatment modalities. Risk stratification and identification of the high risk patients became an essential part of the evaluation in emergency departments.

Angina, Unstable↗
PubMed2006

[Prognostic stratification in non-ST-elevation acute coronary syndromes: how and why].

Prognostic stratification is essential for the correct management of acute coronary syndromes (ACS). Across the whole spectrum of ACS, prognosis is strongly differentiated and also easy to establish. Shock identifies a small subgroup of patients including more than 50% of total mortality of acute ST-elevation myocardial infarction (STEMI). In non-ST-elevation (NSTE) ACS and in STEMI, heart failure represents a clinical variable with a strong prognostic value: in the GRACE registry only 15% of patients had heart failure with a mortality of 12.4 vs 1.1% in the other patients without heart failure; this important difference was interestingly evident in non-STEMI as well as in STEMI. Age is another pivotal risk indicator like heart rate and systolic blood pressure. It is noteworthy that the prognostic benefit deriving from resource utilization increases in ACS with the level of personal risk. This is true for the use of primary angioplasty in national registries of STEMI as well as for the early invasive strategy in NSTE-ACS in several trials; conversely, the use of aggressive strategies in low-risk ACS populations is often lacking of relevant results on hard endpoints. In our healthcare system with limited resources and with an inhomogeneous structure across the country, regionalization of care is the most efficient choice. Scientific Italian Societies redefined risk criteria for ACS in order to ensure priority to complex care for high-risk subgroups.

Acute Disease↗
PubMed2006

Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: Noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease.

This review deals with noninvasive imaging for risk stratification and with a conceptual approach to the selection of noninvasive tests in patients with suspected or known chronic coronary artery disease (CAD). Already widely acknowledged with SPECT, there is an increasing body of literature data demonstrating that CT coronary calcium assessment is also of prognostic value. The amount of coronary atherosclerosis, as can be extrapolated from CT coronary calcium score, has been shown to be highly predictive of cardiac events. The principal difference between myocardial perfusion SPECT (MPS) and CT coronary calcium for prognostic application appears to be that the former is an excellent tool for assessing short-term risk, thus effectively guiding decisions regarding revascularization. In contrast, the atherosclerosis imaging methods are likely to provide greater long-term risk assessment and, thus, are more useful in determination of the need for aggressive medical prevention measures. Although the more recent development of CT coronary angiography is promising for diagnosis, there has been no information to date regarding the prognostic value of the CT angiographic data. Similarly, cardiac MRI has not yet been adequately studied for its prognostic content. The selection of the most appropriate test for a given patient depends on the specific question being asked. In patients with a very low likelihood of CAD, no imaging test may be required. In screening the remaining asymptomatic patients, atherosclerosis imaging may be beneficial. In symptomatic patients, MPS, CT coronary angiography, and cardiac MRI play important roles. We consider it likely that, with an increased emphasis on prevention and a concomitant aging of the population, many forms of noninvasive cardiac imaging will continue to grow, with nuclear cardiology continuing to grow.

Atherosclerosis↗
PubMed2006

[Prediction value for operative mortality of four different coronary artery bypass graft risk stratification models in Chinese patients].

OBJECTIVE: To assess the prognostic accuracy for operative mortality of 4 different risk stratification models in Chinese patients underwent (coronary artery bypass graft) CABG. METHODS: Between 2002 and 2003, all patients undergoing CABG in our institution were prospectively scored for operative mortality using Parsonnet, EuroSCORE, Cleveland and OPR scoring systems and operative mortality was registered. Operative mortality is defined as postoperative death of any cause during hospitalization. Calibration was estimated using the Hosmer-Lemeshow goodness-of-fit test. Discrimination was evaluated using receiver operating characteristic (ROC) curves and area under a ROC curve (AUC). RESULTS: Follow-up was able to be completed in 2251 prospectively scored patients. Registered operative mortality was 1.87% (42/2251). The overall expected mortality calculated by Parsonnet, EuroSCORE, Cleveland and OPR scoring systems were 5.78%, 2.82%, 3.30% and 1.65%, respectively. The actual operative mortality was within the range of 95% confidence interval of OPR model and the other 3 predicted significantly higher operative mortality. Among the four risk scores, Calibration was good in OPR model (chi(2) = 4.842, P = 20.182) and poor in other 3 models (P < 0.001) while discrimination was acceptable in Parsonnet, Cleveland and OPR scoring systems (AUC: 0.711, 0.754, 0.757, respectively) and excellent in EuroSCORE scoring system (0.813). CONCLUSION: For Chinese patients undergoing CABG, OPR scoring system best predicted the operative mortality. All systems could be used to discriminate operative mortality for individual patient.

China↗
PubMed2006

Prognostic stratification of obese patients by stress 99mTc-tetrofosmin myocardial perfusion imaging.

UNLABELLED: Obesity is a major heath problem associated with increased cardiovascular mortality. There are currently no data to support a role for stress imaging techniques in the risk stratification of obese patients. The aim of this study was to assess the independent value of stress 99mTc-tetrofosmin SPECT in predicting mortality and hard cardiac events in obese patients. METHODS: We studied 265 patients with a body mass index greater than 30 kg/m2 by exercise or dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomography. Endpoints during follow-up were cardiac death and death of any cause. RESULTS: The mean patient age (+/-SD) was 59 +/- 10 y, and 110 of the patients were men (42%). The mean body mass index was 37 +/- 7 kg/m2. Scan findings were normal in 113 patients (43%). Myocardial perfusion abnormalities were fixed in 62 patients (23%) and reversible in 90 patients (34%). During a mean follow-up period of 5.5 +/- 2 y, 41 patients (15%) died. Death was considered cardiac in 22 patients (8%). Nonfatal myocardial infarction occurred in 20 patients (7.5%). The annual cardiac death rate was 0.6% in patients with normal perfusion and 3.3% in patients with abnormal perfusion. Patients with a multiple-vessel distribution of abnormalities had a higher cardiac death rate than did patients with a single-vessel distribution (4.1% vs. 2.5%, P < 0.05). The annual mortality rate was 1.3% in patients with normal perfusion and 4.2% in patients with abnormal perfusion. In a multivariate analysis, perfusion abnormalities were independently predictive of cardiac mortality (risk ratio, 3.2; 95% confidence interval, 1.5-6.7) and overall mortality (risk ratio, 2.7; 95% confidence interval, 1.4-4.3). CONCLUSION: Stress 99mTc-tetrofosmin myocardial perfusion imaging is a useful tool for predicting cardiac and overall mortality in obese patients.

Aged↗
PubMed2006

Challenges in the stratification of breast tumors for tailored therapies.

Studying the molecular stratification of breast carcinoma is a real challenge considering the extreme heterogeneity of these tumors. Many patients are now treated following recommendation established at several NIH and St Gallen consensus conferences. However a significant fraction of these breast cancer patients do not need adjuvant chemotherapies while other patients receive inefficacious therapies. High density gene expression arrays have been designed to attempt to establish expression profiles that could be used as prognostic indicators or as predictive markers for response to treatment. This review is intended to discuss the potential value of these new indicators, but also the current weaknesses of these new genomic and bioinformatic approaches. The combined analysis of transcriptomic and genomic alteration data from relatively large numbers of well annotated tumor specimens may offer an opportunity to overcome the current difficulties in validating recently published non overlapping gene lists as prognostic or therapeutic indicators. There is also hope for identifying and deciphering signal transduction pathways driving tumor progression with newly developed algorithms and semi quantitative parameters obtained in simplified in vitro or in vivo models for specific transduction pathways.

Animals↗
PubMed2005

Risk stratification for sudden cardiac death in patients with non-ischemic dilated cardiomyopathy.

Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge. Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice.

Journal Article↗
PubMed1996

The relationships among adhesion, stratification and differentiation in keratinocytes.

Epidermis is a self-renewing, multilayered tissue composed primarily of keratinocytes. The epidermal keratinocyte follows a terminal differentiation pathway that under normal circumstances is tightly linked to its position within the epidermis and culminates in the formation of the protective barrier (stratum corneum) that constitutes the outermost layer of skin. Strong but pliant adhesive mechanisms are essential for normal functioning of the epidermis. In the epidermis, adhesion is mediated primarily by four structures: hemidesmosomes and focal adhesions, which function in cell-matrix adhesion, and desmosomes and adherens junctions, which function in cell-cell adhesion. In this review we concentrate on the transmembrane components of these structures, which are thought to mediate directly the adhesive function. Members of the integrin family of adhesion molecules comprise the transmembrane components of hemidesmosomes and focal adhesions, although hemidesmosomes also have a second, unrelated transmembrane molecule known as 'bullous pemphigoid antigen 2'. Members of the cadherin family are the transmembrane constituents of desmosomes and adherens junctions. Desmosomes consistently contain two types of cadherins (desmoglein and desmocollin), while adherens junctions may contain only one type of cadherin (E- or P-cadherin). Expression of most of the transmembrane components varies with the position of the keratinocyte within the epidermis and thus may reflect the degree of epidermal differentiation. All of the integrin subunits have been localized predominantly to the basal layer. In contrast, the cadherins show very complex expression patterns throughout the epidermis. Desmogleins and desmocollins (the desmosomal cadherins) are each encoded by three genes, and the expression of each gene is limited to certain epidermal layers. With respect to the cadherins of the adherens junction, it has been shown that E-cadherin is present throughout the epidermis, while P-cadherin is limited to the basal layer. Interestingly, these complex expression patterns of integrins and cadherins within the epidermis may not simply be passive events in differentiation; rather, evidence is accumulating that adhesion molecules can exert a dynamic role in epidermal differentiation/stratification. For example, decreased adhesion to extracellular matrix, induced by changes in one or more integrins, appears to be a signal that induces certain differentiation-related events. Even more profound effects on epidermal morphogenesis have been demonstrated for the cadherins. E- and/or P-cadherin is required not only to initiate normal intercellular junction formation but also for the subsequent development of a stratified epithelium. Thus, the findings to date with both integrins and cadherins suggest that adhesion molecules may function not just as direct mediators of adhesion, but also as regulators of epidermal stratification, differentiation, and morphogenesis.

Journal Article↗