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PubMed2002

Phenotypic spectrum of interstitial 7p duplication in mosaic and non-mosaic forms.

The phenotypes of a mother and child with a duplication of 7p15-7p22 are described. The mother is mosaic for the cytogenetic abnormality, whereas all cells are affected in her son. Fewer than 5 patients with interstitial 7p duplications are described in the world literature whereas over 30 phenotypic descriptions of individuals with terminal 7p duplication can be found. Authors have suggested that the associated phenotype amounts to a recognizable syndrome. The current cases give further insights into the phenotype that results from pure 7p duplication, both in its mosaic and in its full form. Comparisons are made with previous cases, in the light of the shorter segment involved in the current patients, whose duplication does not extend to pter. This case description will be useful in counseling patients with duplications of 7p and lends support to the existence of characteristic craniofacial features and congenital malformations in this chromosome rearrangement. In addition, as earlier case reports all describe the phenotype associated with non-mosaic partial 7p trisomy, the current observations amount to clear evidence that mosaicism attenuates the phenotype of this rearrangement.

Adult↗
PubMed2002

Genotype-phenotype correlation in cystic fibrosis: the role of modifier genes.

More than 1,000 mutations have been identified in the cystic fibrosis (CF) transmembrane regulator (CFTR) disease gene. The impact of these mutations on the protein and the wide spectrum of CF phenotypes prompted a series of Genotype-Phenotype correlation studies. The CFTR genotype is invariably correlated with pancreatic status-in about 85% of cases with pancreatic insufficiency and in about 15% of cases with pancreatic sufficiency. The correlations between the CFTR genotype and pulmonary, liver, and gastrointestinal expression are debatable. The heterogeneous phenotype in CF patients bearing the same genotype or homozygotes for nonsense mutations implicated environmental and/or genetic factors in the disease. However, the discordant phenotype observed in CF siblings argued against a major role of environmental factors and suggested that genes other than CFTR modulate the CF phenotype. A locus that modulates gastrointestinal expression was identified in mice and subsequently in humans. By analyzing nine CF patients discordant for meconium ileus we were able to show that this locus had a dominant effect. Moreover, in a collaborative study we found a higher rate of polymorphisms in beta-defensin genes 1 and 2 in CF patients and in controls. In another multicenter study mutations in alpha-1 antitrypsin (A1AT) and mannose binding lectin genes were found to be independent risk factors for liver disease in CF patients. The body of evidence available suggests that the variegated CF phenotype results from complex interactions between numerous gene products.

Animals↗
PubMed1990

Partial trisomy 18 with minimal anomalies: lack of correspondence between phenotypic manifestations and triplicated loci along chromosome 18.

A 2-year-old boy with microcephaly, developmental delay, and minimal anomalies was found to have an extra submetacentric chromosome equivalent to 18pter----q12. Review of the phenotypes produced by various triplicated 18 regions supports the hypothesis that no one chromosome 18 region is sufficient to produce the phenotype of trisomy 18. The mild phenotype of trisomy 18p, the variable phenotype of trisomy 18pter----q12, and the discontinuous phenotype of triplication for band 18q12 alone emphasizes that the contribution of triplicated loci to the phenotype is neither additive nor invariant.

Child, Preschool↗
PubMed1993

Interrelationships of the hemifacial microsomia-VATER, VATER, and sirenomelia phenotypes.

The phenotypes of hemifacial microsomia-VATER, VATER, and sirenomelia patients suggest a sequence of overlapping developmental abnormalities. The malformations of 247 hemifacial microsomia (HFM) patients with one or more anomalies in other body regions were analyzed and compared with those of 255 VATER and 101 sirenomelia patients studied in the same fashion. The HFM patients were analyzed in four subgroups delineated by the number of their concomitant VATER ascertainment abnormalities (VAA). Three or more VAA occurred in 33 HFM patients who were designated to have the HFM-VATER phenotype and while no significant alteration of the HFM phenotype was found, there were notable differences in the analyses of the 20 malformation categories studied. Analyzed in separate heart and blood vessel (BV) categories, occurrences of BV defects in HFM patients with 0-1 VAA were low (4-6%) and due to anomalies other than single umbilical arteries (SUA). The BV abnormalities increased to 20% in the HFM with two VAA, HFM-VATER, and VATER phenotypes with equal occurrences of SUA and other BV anomalies. The incidence of SUA was markedly increased (64%) in the sirenomelia. Heart defects rose from 22% to 40% with the increasing VAA in individual HFM patients but were less in VATER (29%) and sirenomelia (21%) patients and were attributed to complex, conotruncal, and other early embryonic anomalies. Unilateral agenesis of paired organs systems occurred frequently and, possibly, can be attributed to an absent blood supply. Each phenotype of the sequence also had increased VAA, rib/vertebrae hypersegmentation, and monozygotic twinning. The variation in the incidences of malformations in the three phenotypes can be attributed to their relative location in the craniocranial organogenesis sequence of normal human embryologic development.

Abnormalities, Multiple↗
PubMed2005

Precision and error of three-dimensional phenotypic measures acquired from 3dMD photogrammetric images.

The genetic basis for complex phenotypes is currently of great interest for both clinical investigators and basic scientists. In order to acquire a thorough understanding of the translation from genotype to phenotype, highly precise measures of phenotypic variation are required. New technologies, such as 3D photogrammetry are being implemented in phenotypic studies due to their ability to collect data rapidly and non-invasively. Before these systems can be broadly implemented, the error associated with data collected from images acquired using these technologies must be assessed. This study investigates the precision, error, and repeatability associated with anthropometric landmark coordinate data collected from 3D digital photogrammetric images acquired with the 3dMDface System. Precision, error due to the imaging system, error due to digitization of the images, and repeatability are assessed in a sample of children and adults (n = 15). Results show that data collected from images with the 3dMDface System are highly repeatable and precise. The average error associated with the placement of landmarks is sub-millimeter; both the error due to digitization and due to the imaging system are very low. The few measures showing a higher degree of error include those crossing the labial fissure, which are influenced by even subtle movement of the mandible. These results suggest that 3D anthropometric data collected using the 3dMDface System are highly reliable and, therefore, useful for evaluation of clinical dysmorphology and surgery, analyses of genotype-phenotype correlations, and inheritance of complex phenotypes.

Adult↗
PubMed2004

Patterns of phenotypic covariation and correlation in modern humans as viewed from morphological integration.

Proportionality of phenotypic and genetic distance is of crucial importance to adequately focus on population history and structure, and it depends on the proportionality of genetic and phenotypic covariance. Constancy of phenotypic covariances is unlikely without constancy of genetic covariation if the latter is a substantial component of the former. If phenotypic patterns are found to be relatively stable, the most probable explanation is that genetic covariance matrices are also stable. Factors like morphological integration account for such stability. Morphological integration can be studied by analyzing the relationships among morphological traits. We present here a comparison of phenotypic correlation and covariance structure among worldwide human populations. Correlation and covariance matrices between 47 cranial traits were obtained for 28 populations, and compared with design matrices representing functional and developmental constraints. Among-population differences in patterns of correlation and covariation were tested for association with matrices of genetic distances (obtained after an examination of 10 Alu-insertions) and with Mahalanobis distances (computed after craniometrical traits). All matrix correlations were estimated by means of Mantel tests. Results indicate that correlation and covariance structure in our species is stable, and that among-group correlation/covariance similarity is not related to genetic or phenotypic distance. Conversely, genetic and morphological distance matrices were highly correlated. Correlation and covariation patterns were largely associated with functional and developmental factors, which probably account for the stability of covariance patterns.

Alu Elements↗
PubMed2001

Regaining chondrocyte phenotype in thermosensitive gel culture.

Chondrocyte tissue engineering continues to be a challenging problem. When chondrocytes are duplicated in vitro, it is imperative to obtain an adequate number of cells of optimal phenotype. A temperature-sensitive polymer gel, a copolymer of poly(N-isopropylacrylamide) and acrylic acid (PNiPAAm-co-Aac), has the ability of gelling at 37 degrees C (the lower critical solution temperature, LCST) or above and liquefying below that temperature (Vernon and Gutowska, Macromol. Symp. 1996;109:155-167). The hypothesis of this study was that chondrocytes could (1) duplicate in the copolymer gel; (2) regain their chondrocyte phenotype; and (3) be easily recovered from the gel by simply lowering the temperature below 37 degrees C. Chondrocytes from adult rabbit scapular cartilage were harvested and cultured in a monolayer culture until confluency (approximately 2 weeks). Next, the cells were harvested and seeded into the copolymer gel and cultured for 2-4 weeks. The phenotype of the cultured cells was then characterized. Two groups of control cultures, monolayer and agarose gel, were used to compare their ability to maintain chondrocyte phenotype. The results showed that chondrocytes isolated from rabbit scapula can re-express chondrocyte phenotype in agarose culture and polymer gel culture but not in monolayer culture. Also, cultured chondrocytes can be easily recovered from polymer gel culture by simply lowering the temperature. This new in vitro method of chondrocyte culture is recommended for chondrocyte propagation and regaining chondrocyte phenotype before cell seeding or transplantation.

Acrylamide↗
PubMed1995

Strategies for pharmacologic modulation of the heart failure phenotype.

The end-stage heart failure phenotype is characterized by marked dyspnea on exertion, edema, and overwhelming fatigue, and by a high incidence of sudden death. Patients who display the end-stage phenotype have transitioned from a normal phenotype with myocardial damage at a cellular level. This transition appears to be mediated by events at both the cellular and molecular levels. Until recently, it was generally believed that this transition was irreversible. However, recent clinical trials have demonstrated that the phenotype can be changed with pharmacologic agents. These agents have been demonstrated to improve exercise capability, increase ventricular function, and improve symptoms. Important recent studies have shown that pharmacologic agents can substantially alter the high mortality rates associated with the end-stage heart failure phenotype. As we learn more about the molecular and cellular events that initiate and support the transition from cardiac compensation to decompensation, we will be able to improve our pharmacologic targeting and, we hope, be able to delay the development of the end-stage heart failure phenotype to an even greater degree.

Adrenergic beta-Antagonists↗
PubMed2002

The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research.

The investigation of genetic alterations that may be related to the prognosis of patients with malignant disease has become a frequently used strategy in recent years. Although some conclusions have been reached in certain studies, the complexity and the multifactorial nature of most neoplastic diseases makes it difficult to identify clinically relevant information, and the results of some studies have been of borderline significance or have been conflicting. In contrast, the identification and the study of patients or families with very characteristic phenotypes have yielded outstanding results in the identification of the genetic characteristics underlying such phenotypes. Although, in most cases, the individuals who are selected for these types of studies are characterized by a negative phenotype (i.e., individuals who are at increased risk for developing a specific disease), a few studies have been directed toward individuals with phenotypes that imply an unusually good prognosis (i.e., individuals who present with a decreased risk for developing specific diseases despite an important exposure to well-known risk factors). Therefore, it seems logical to develop this strategy further as a valid methodology for the study of other diseases, such as cancer. The study of individuals with phenotypes that imply an extremely good prognosis, such as long-term survivors of theoretically incurable malignancies or individuals who seem to be protected against a certain neoplastic disorder despite having a markedly increased risk for its development, may unveil genetic alterations that explain such characteristic phenotypes and may provide potentially useful therapeutic targets against these diseases.

Genetic Markers↗
PubMed2004

The replication error phenotype is associated with the development of distant metastases in hormonally treated patients with breast carcinoma.

BACKGROUND: The positive replication error (RER+) phenotype defines a distinct subgroup of tumors with specific clinical, pathologic, and molecular features that have been documented well in hereditary nonpolyposis colon carcinoma (HNPCC). More recently, this phenotype also has been described in breast carcinoma. METHODS: To determine the effect of RER phenotype on prognosis in patients with breast carcinoma, the authors examined matched archival tumor and normal tissue from 100 women with Stage I and Stage II breast carcinoma, all of whom were treated with hormonal therapy. Patients had been followed for a minimum of 5 years or until death. Seven microsatellite loci were examined, including hMLH1 (3p22, D3S1611), hMSH2 (2p16, D2S123), NM23-H1 (17q21), TP53-Dint (17p13), TP53-Penta (17p13), APC (5q21, D5S346), and HPC1 (1q24, D1S2883). The RER+ phenotype was defined as the presence of allelic shifts at three of the seven loci examined. RESULTS: Twenty-five percent of patients were classified with the RER+ phenotype based on these criteria. The two groups, women with positive RER status and women with negative RER status, were comparable in terms of other factors that may influence prognosis: age, tumor size, lymph node status, disease stage, and estrogen receptor status. The development of distant metastases to the lung, liver, or brain was correlated significantly with the positive RER phenotype, with a relative risk of 2.625 (95% confidence interval, 1.059-6.057). CONCLUSIONS: The presence of high-frequency RER+ may predict for the development of distant metastatic disease in patients with early-stage breast carcinoma who are treated with hormonal therapy.

Aged↗
PubMed2003

Removing phenotypic distribution assumptions from tests of linkage disequilibrium for quantitative traits.

The transmission disequilibrium test (TDT) has become a family-based method of reference to search for linkage disequilibrium (LD). Although it was first developed for dichotomous traits, numerous approaches have extended the TDT to quantitative phenotypes that either rely on regression or variance component techniques. Both of these approaches are based on some phenotypic distribution assumptions, the violation of which can lead to inflation of type I error rates, and derive information from phenotypic variability, so that their power is very low under some selection schemes (e.g., one-tailed selection). We propose a new family-based test of association for quantitative traits, denoted maximum-likelihood-binomial (MLB)-QTDT, which addresses the two previous issues by incorporating a latent binary variable that captures the LD information between the marker allele and the quantitative phenotype. The method can be understood as a classical TDT for binary traits that would include pure affected and pure unaffected children, and the probability for a child to be affected or unaffected depends on his/her quantitative phenotypic value. Simulation studies under the null hypothesis show that the MLB-QTDT provides very consistent type I errors even in small and/or selected samples. Under the alternative hypothesis, the MLB-QTDT has good power to analyze one-tailed selected samples, and performs as well as a classical approach in other designs. The MLB-QTDT is a flexible distribution-free method to test for LD with quantitative phenotypes in nuclear families, and can easily incorporate previous extensions developed in the context of family-based association studies with binary traits.

Alleles↗
PubMed1989

The distribution of debrisoquine metabolic phenotypes and implications for the suggested association with lung cancer risk.

Debrisoquine hydroxylation exhibits wide inter-individual variation in Caucasian populations. After similar doses of the drug, extensive metabolizers excrete up to several hundred times more of the urinary metabolite 4-hydroxy-debrisoquine than do poor metabolizers. The phenotypes have traditionally been defined by the metabolic ratio (MR), or the molar ratio of debrisoquine to its chief metabolite recovered in an aliquot of an eight hour urine sample, after a test dose of the drug. Deficient metabolism is inherited as an autosomal recessive condition. We have reanalyzed previously published data from a study of lung cancer patients and controls using a computerized optimization method to more accurately estimate the parameters describing the three phenotypic distributions. Using these new distributions to categorize controls, we show that Hardy-Weinberg conditions are now fulfilled. When the newly defined phenotype parameters are employed to assign the phenotypes of cases and controls, a highly significant difference in phenotype distribution between cases and controls is still observed. This result supports the hypothesis that the debrisoquine metabolic phenotype may be associated with lung cancer susceptibility.

Chromatography, Gas↗
PubMed1989

Phenotypic effects of apolipoprotein structural variation on lipid profiles. IV. Apolipoprotein polymorphisms in a small group of black women from the healthy women study.

Structural variation in apolipoprotein E has been shown to influence lipid and lipoprotein concentrations. The purpose of the present study was to investigate several apolipoproteins in a group of Black women from the Healthy Women Study (HWS). HWS is a community-based prospective study of 541 premenopausal women who are being followed through the menopause to determine the influence of biological, genetic, and psychosocial phenomenon on cardiovascular risk factors. Of the 541 subjects, 48 are Black. Serum from most of these 48 Black women was used to type seven apolipoproteins (APO A-I, APO A-II, APO A-IV, APO C-II, APO D, APO E, and APO H). Five of these apolipoproteins are polymorphic in Blacks (APO A-IV, APO C-II, APO D, APO E and APO H). Only two and three individuals, respectively, were heterozygous at the APO D and APO C-II loci. APO A-IV, E, and H exhibited more variation, however, only APO E phenotypes could be used for statistical analyses. Three common phenotypes, APO E 3-2, APO E 3-3, and APO E 4-3, were used in analysis of variance on four quantitative lipid variables. Despite small numbers, the effect of APO E phenotype was apparent. The APO E 3-2 phenotype showed reduced average levels of total cholesterol, apolipoprotein B (APO B) and low-density lipoprotein cholesterol (LDLc), and the APO E 4-3 phenotype showed increased levels (P less than or equal to .0497). The APO E3-3 homozygote was intermediate on all three. Because of small numbers in the cells of APO A-IV and APO H phenotypes, these were not analyzed with respect to quantitative lipids.

Adult↗
PubMed1991

Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia.

Low-density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small, dense LDL particles, appears to be a genetically influenced risk factor for coronary heart disease. Phenotype B, as determined by gradient gel electrophoresis, appears to be inherited in a manner consistent with the presence of a single major genetic locus, based on complex segregation analysis. Familial combined hyperlipidemia (FCHL) is a disorder characterized by elevations in total plasma cholesterol and/or triglyceride levels in probands and family members, variable lipoprotein phenotypes over time, and elevations in apolipoprotein B levels. Because apo B is the primary protein component of LDL particles, the present study was undertaken to determine whether LDL subclass phenotypes are controlled by the APOB locus in FCHL families. The evidence against linkage was very strong based on lod score analyses (total lod = -13.3), under assumptions that LDL subclass phenotypes are influenced by a major genetic locus and that the mode of inheritance and penetrance functions are known. Other methods requiring fewer assumptions also provided evidence against linkage, although the strength of this evidence was weaker. Thus the results demonstrate that the proposed gene responsible for LDL subclass phenotypes is unlikely to be the APOB gene in families with FCHL.

Alleles↗
PubMed1994

Segregation analyses of four urinary caffeine metabolite ratios implicated in the determination of human acetylation phenotypes.

Human acetylation phenotypes were determined with caffeine (137X) as the test substance, improved by measuring urinary caffeine metabolites with a previously described HPLC method. Caffeine, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (IX), 1-methyluric acid (IU), 1,7-dimethylxanthine (17X), and 1,7-dimethyluric acid (17U) were quantified. This study tested the hypothesis, suggested by previous studies, that the acetylation polymorphism is strongly influenced by a major gene. Phenotypes were assessed by using four urinary caffeine metabolite ratios: AFMU/1X, AFMU/[1X + 1U + 17U], AFMU/[AFMU + 1X + 1U], and AFMU/[1X + 1U + 17X + 17U] in a population included 281 nuclear family members who were healthy volunteer subjects. Each urinary ratio revealed strong familial aggregation with correlations between parents and offspring varying from 0.340 to 0.486 as a function of the ratio considered, and between sibs from 0.410 to 0.512 whereas correlations among spouses were not significant, excluding an effect of environmental factors. Segregation analyses were conducted upon these four ratios testing a series of specific models of inheritance and gave evidence for single locus control of N-acetyltransferase (NAT) activity, with Mendelian codominant transmission using the AFMU/1X, AFMU/[1X + 1U + 17U], and AFMU/[1X + 1U + 17X + 17U] ratios. The slow allelic frequencies were 0.739, 0.753, and 0.724, respectively, and the phenotypic concordance was 90 to 92% with the AFMU/1X ratio. The familial aggregation observed in using the AFMU/[AFMU + 1X + 1U] ratio was consistent with a recessive transmission for the allele controlling the homozygous slow phenotype. This last ratio is not convenient to differentiate rapid heterozygous and homozygous phenotype. Considering the number of misclassified subjects, this study would be completed by genotyping the same families as demonstrated by some authors who predicted 97.5% of acetylation phenotype when using PCR-based DNA amplification test.

Acetylation↗
PubMed2001

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance.

Mutations in the DTDST gene can result in a family of skeletal dysplasia conditions which comprise two lethal disorders, achondrogenesis type 1B (ACG1B) and atelosteogenesis type 2 (AO2); and two non-lethal disorders, diastrophic dysplasia (DTD) and recessive multiple epiphyseal dysplasia (rMED). The gene product is a sulfate-chloride exchanger of the cell membrane. Inactivation of the sulfate exchanger leads to intracellular sulfate depletion and to the synthesis of undersulfated proteoglycans in susceptible cells such as chondrocytes and fibroblasts. Genotype-phenotype correlations are recognizable, with mutations predicting a truncated protein or a non-conservative amino acid substitution in a transmembrane domain giving the severe phenotypes, and non-transmembrane amino acid substitutions and splice site mutations giving the milder phenotypes. The clinical phenotype is modulated strictly by the degree of residual activity. Over 30 mutations have been observed, including 22 novel mutations reported here. The most frequent mutation, 862C>T (R279W), is a mild mutation giving the rMED phenotype when homozygous and mostly DTD when compounded; occurrence at a CpG dinucleotide and its panethnic distribution suggest independent recurrence. Mutation IVS1+2T>C is the second most common mutation, but is very frequent in Finland. It produces low levels of correctly spliced mRNA, and results in DTD when homozygous. Two other mutations, 1045-1047delGTT (V340del) and 558C>T (R178X), are associated with severe phenotypes and have been observed in multiple patients. Most other mutations are rare. Heterozygotes are clinically unaffected. When clinical samples are screened for radiologic and histologic features compatible with the ACG1B/AO2/DTD/rMED spectrum prior to analysis, the mutation detection rate is high (over 90% of alleles), and appropriate genetic counseling can be given. The sulfate uptake or sulfate incorporation assays in cultured fibroblasts have largely been replaced by mutation analysis, but may still be useful in cases where mutation analysis is not informative. Although supplementation of patients' cultured cells with thiols may bypass the transporter defect and enhance sulfation of proteoglycans, therapeutic approaches are not yet available. Mouse models for this and other disorders of sulfate metabolism are being developed to help in developing therapeutic treatments.

Animals↗
PubMed2003

Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.

The mitochondrial trifunctional protein (TFP) is a multienzyme complex of the fatty acid beta-oxidation cycle. It is composed of four alpha-subunits (HADHA) harboring long-chain enoyl-CoA hydratase and long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) and four beta-subunits (HADHB) harboring long-chain 3-ketoacyl-CoA thiolase (LKAT). Mutations in either subunit can result in TFP deficiency with reduced activity of all three TFP enzymes. We characterize 15 patients from 13 families with beta-subunit mutations by clinical, biochemical, and molecular features. Three clinical phenotypes are apparent: a severe neonatal presentation with cardiomyopathy, Reye-like symptoms, and early death (n=4); a hepatic form with recurrent hypoketotic hypoglycemia (n=2); and a milder later-onset neuromyopathic phenotype with episodic myoglobinuria (n=9). Maternal HELLP syndrome occurred in two mothers independently of the fetal phenotype. Mutational analysis revealed 16 different mutations, the majority being missense mutations (n=12). The predominance of missense mutations and the milder myopathic phenotype are consistent. Based upon homology to yeast thiolase that has been characterized structurally, the mutation localization within the protein correlates with the clinical phenotype. Outer loop mutations that are expected to alter protein stability less were only present in milder forms. The degree of reduction in thiolase antigen also correlated with the severity of clinical presentation. Although TFP deficiency is highly heterogeneous, there is genotype-phenotype correlation.

Adolescent↗
PubMed2003

Breast cell invasive potential relates to the myoepithelial phenotype.

On the basis of marker profile, the majority of breast carcinomas are thought to be derived from luminal epithelial cells; however, a subgroup of tumours with more mesenchymal characteristics are associated with a worse prognosis. The hypothesis of our study is that some breast carcinomas exhibit myoepithelial rather than pure mesenchymal differentiation and that acquisition of myoepithelial characteristics confers an aggressive phenotype. Pure luminal epithelial cells and fibroblasts are readily distinguished by many markers but distinguishing between myoepithelial and fibroblast cell lineages is more problematic. The markers found to be most discriminating in our study were CK14, alpha6beta4 integrin and the myoepithelial-associated desmosomal cadherin DSg3. These markers were applied to a series of breast cell lines and purified normal breast cell populations and the expression profile related to in vitro invasive behaviour. This demonstrated that expression of one or more myoepithelial markers by tumour cells (MDA MB 231, MDA MB 468, MDA MB 436) was associated with a high invasive capacity compared with cells with a pure luminal phenotype (MCF-7, T47D, ZR75). To address why myoepithelial characteristics are associated with higher invasion, the in vitro behaviour of normal myoepithelial cells and two other nontumourigenic breast cell lines (MCF-10A, HBL100) was also analysed. Primary myoepithelial cells from normal human breast exhibit a high invasive capacity when grown at low density, suggesting that invasive capacity is part of the myoepithelial phenotype. In keeping with this, both nontumourigenic cell lines exhibited features of the myoepithelial phenotype and a high invasive capacity. These results suggest that tumours that exhibit a myoepithelial phenotype may be clinically more aggressive because a high invasive capacity is intrinsic to the myoepithelial phenotype.

Antigens↗