Influence of Cytochrome P450, ABC and SLC Gene Polymorphisms on Imatinib Therapy Outcome of Patients with Gastrointestinal Stromal Tumours (GIST).

The efficacy of imatinib-based therapy depends on the proteins involved in its metabolism and transportation. Therefore, the aim of our study was to investigate the possible correlation of selected P450, ABC and SLC polymorphic variants and the outcome of imatinib therapy. A total of 101 patients with advanced, KIT/PDGFRA(+) GIST treated with imatinib were enrolled to the study. DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP and direct sequencing. Deviation from the Hardy-Weinberg equilibrium was only observed for rs2740574. None of the studied SNPs was associated with GIST time to progression. No significant correlation between any specific variant and time to progression was found in the group with KIT exon 11 mutation. However, individuals of at least three potentially unfavourable genotypes presented significantly shorter time to progression in comparison to patients with two or less unfavourable genotypes.

Electrostrictive and piezoelectrical properties of chitosan-poly(3-hydroxybutyrate) blend films.

Herein, we report the high apparent piezoelectric coefficient for chitosan-poly(3-hydroxybutyrate) (CS-PHB) blend films. The structure of chitosan-poly(3-hydroxybutyrate) (CS-PHB) blend films, exploiting characteristics such as dielectric, polarization, apparent piezoelectric properties, and their dependencies on the composition, were investigated. Based on the results of XRD, SEM, FTIR, PFM, and dielectric spectroscopy measurements, the structure of CS-PHB blend films has been proposed, which consists of spheric-like inclusion formed by precipitating isotactic-PHB interface layer, which consists of syndiotactic-PHB hydrogen bonding with CS, and CS matrix. The synergistic effects of piezoelectricity and electrostriction help explain the high value of the apparent piezoelectric coefficient (d33) obtained in the blend film with 13 wt% of PHB (d33 ≈ 200 pC/N). The investigated CS-PHB blend films are a good candidate for tissue engineering applications.

Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience.

BACKGROUND: Majority of gastrointestinal stromal tumours (GISTs) are characterised by KIT-immunopositivity and the presence of KIT/platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. PATIENTS AND METHODS: Spectrum and frequency of KIT and PDGFRA mutations were investigated in 427 GISTs. Univariate and multivariate analysis of relapse-free survival (RFS) was conducted in relation to tumours' clinicopathologic features and genotype. RESULTS: Mutations were found in 351 (82.2%) cases, including 296 (69.3%) KIT and 55 (12.9%) PDGFRA isoforms. Univariate analysis revealed higher 5-year RFS rate in women (37.9%; P = 0.028) and in patients with gastric tumours (46.3%; P < 0.001). In addition a better 5-year RFS correlated with smaller tumour size ≤ 5 cm (62.7%; P < 0.001), tumours with mitotic index ≤ 5/50 high-power fields (60%; P < 0.001), and characterised by (very) low/moderate risk (70.2%; P = 0.006). Patients with GISTs bearing deletions encompassing KIT codons 557/558 had worse 5-year RFS rate (23.8%) than those with any other KIT exon 11 mutations (41.8%; P < 0.001) or deletions not involving codons 557/558 (33.3%; P = 0.007). Better 5-year RFS characterised patients with KIT exon 11 point mutations (50.7%) or duplications (40%). By multivariate analysis, tumours with PDGFRA mutations and KIT exon 11 point mutations/other than 557/558 deletions had lower risk of progression than with KIT exon 11 557/558 deletions (both Ps = 0.001). CONCLUSIONS: KIT/PDGFRA mutational status has prognostic significance for patients' outcome and may help in management of patients with GISTs.

Maternal reproductive history and the risk of isolated congenital malformations.

We examined the relationship between maternal reproductive history and the newborn's risk of isolated congenital malformations in a large case-control cohort from the Polish Registry of Congenital Malformations. Congenital malformations were classified into four categories: isolated congenital heart defects (n=1673), isolated cleft palate (n=255), cleft lip with or without cleft palate (n=448) and renal agenesis (n=103). The case groups were compared with a shared group of 2068 controls recruited in the same time period and geographic area. Multivariable logistic regression was used to assess the risk associated with maternal gravidity and of previous miscarriages after accounting for maternal age and other potential risk factors. In unadjusted analyses, maternal gravidity was significantly associated with increased risk of all four classes of congenital malformations. After adjustment, a significant association persisted for congenital heart defects [odds ratio (OR)=1.22, [95% confidence interval (CI) 1.09, 1.36], P=0.0007] and cleft lip with or without cleft palate (OR=1.21, [95% CI 1.09, 1.36], P=0.0005). A similar trend existed for isolated cleft palate (OR=1.18, [95% CI 1.02, 1.37], P=0.03). There was no appreciable increase in the risk of congenital malformations associated with a maternal history of miscarriages, but a trend for a protective effect on the occurrence of cleft lip with or without cleft palate was observed (OR=0.72, [95% CI 0.52, 0.99], P=0.045). Based on our data, maternal gravidity represents a significant risk factor for congenital heart defects and cleft lip with or without cleft palate in the newborn infant. Our data do not support an increase in risk because of past history of miscarriages.

8.6Mb interstitial deletion of chromosome 4q13.3q21.23 in a boy with cognitive impairment, short stature, hearing loss, skeletal abnormalities and facial dysmorphism.

We describe a 16-year-old boy with an 8.6Mb interstitial deletion of chromosome 4q 13.3q21.23 identified by oligo array-CGH. The patient presents psychomotor developmental delay, absent speech, marked progressive growth restriction, hearing loss, skeletal defects and minor facial anomalies. The patient required surgical treatment for cleft lip and palate, bilateral cryptorchidism and a neurofibroma. The analysis of the presented patient against previously published cases allowed us to expand further on the phenotype and to reevaluate previously proposed critical overlapping region at 4q21. As an addition to PRKG2 and RASGEFIB genes, we propose to include BMP3 gene as the principal determinant of the observed common phenotype. BMP3 haploinsufficiency appears to be causative of hearing loss and peculiar skeletal abnormalities including hemivertebrae and brachydactyly.

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations.

Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated ADH patients, to explore the mutation spectrum that causes hypercholesterolemia in Poland. All patients were clinically diagnosed with ADH according to a uniform protocol and internationally accepted WHO criteria. Mutational analysis included all exons, exon-intron boundaries and the promoter sequence of the LDLR, and a fragment of exon 26 of APOB. Additionally, the MLPA technique was applied to detect rearrangements within LDLR. In total, 100 sequence variations were identified in 234 (62%) patients. Within LDLR, 40 novel and 59 previously described sequence variations were detected. Of the 99 LDLR sequence variations, 71 may be pathogenic mutations. The most frequent LDLR alteration was a point mutation p.G592E detected in 38 (10%) patients, followed by duplication of exons 4-8 found in 16 individuals (4.2%). Twenty-five cases (6.6%) demonstrated the p.R3527Q mutation of APOB. Our findings imply that major rearrangements of the LDLR gene as well as 2 point mutations (p.G592E in LDLR and p.R3527Q in APOB) are frequent causes of ADH in Poland. However, the heterogeneity of LDLR mutations detected in the studied group confirms the requirement for complex molecular studies of Polish ADH patients.

Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene.

Weight gain, a serious problem associated with some antipsychotic drugs, notably olanzapine and clozapine, was suggested to be associated with -759C/T polymorphism of the 5-HT2C receptor gene. This study aimed to examine a potential association of two functional polymorphisms of the promoter region of this gene: -759C/T (rs3813929) and -697G/C (rs518147), with weight gain after 6 weeks of olanzapine monotherapy. It included 107 patients with schizophrenia; among them 36 are first-episode drug-naive patients. Analysis was carried out by PCR-restriction fragment length polymorphism. A protective effect of -759T and -697C alleles was found: significantly less patients with -697C (3/51) and no patient with -759T (0/28) alleles experienced body mass index increase >or=10% (P=0.0006 and 0.002, respectively). The same was true for drug-naive patients possessing any of the variant alleles. There was a significant association of haplotypes with a >or=10% body mass index increase (P=0.001). On the basis of the additional statistical analysis, the more important role of -697C allele was suggested.

Loss of heterozygosity at BRCA1/2 loci in hereditary and sporadic ovarian cancers.

Loss of heterozygosity at BRCA1/2 loci in breast and ovarian tumors is a suggested risk factor for germline BRCA1/2 mutation status. We evaluated the presence of losses of selected microsatellite markers localized on chromosomes 17 and 13q in hereditary and sporadic ovarian tumors. 151 consecutive primary ovarian tumors (including 21 with BRCA1/2 mutations and 130 without the mutations) were screened for loss of heterozygosity at loci on chromosomes 17 and 13q. Losses of heterozygosity of at least one microsatellite marker localized on chromosomes 17 and 13q were revealed in 123 (81.5%) and 104 (68.9%) tumors, respectively. Losses of all informative markers on chromosomes 17 and 13 occurred in 30 (19.9%) and 31 (20.5%) tumors, respectively. There was no difference in the frequency of losses at BRCA1 intragenic markers (D17S855 and D17S1323) between BRCA1-positive and BRCA1-negative patients. The frequency of losses on chromosome 17 was higher in high-grade than in low-grade carcinomas. Loss of heterozygosity on chromosomes 17 and 13q is a frequent phenomenon in both hereditary and sporadic ovarian cancers. The frequency of losses at BRCA1 intragenic markers in the ovarian tumor tissue is not strongly related to the presence of BRCA1 germline mutations.

Testing of a scanning adiabatic calorimeter with Joule effect heating of the sample.

We evaluated a scanning adiabatic resistive calorimeter (SARC) developed to measure the specific enthalpy of viscous and gel-type materials. The sample is heated employing the Joule effect. The cell is constituted by a cylindrical jacket and two pistons, and the sample is contained inside the jacket between the two pistons. The upper piston can slide to allow for thermal expansion and to keep the pressure constant. The pistons also function as electrodes for the sample. While the sample is heated through the Joule effect, the electrodes and the jacket are independently heated to the same temperature of the sample using automatic control. This minimizes the heat transport between the sample and its surroundings. The energy to the sample is supplied by applying to the electrodes an ac voltage in the kilohertz range, establishing a current in the sample and inducing electric dissipation. This energy can be measured with enough exactitude to determine the heat capacity. This apparatus also allows for the quantification of the thermal conductivity by reproducing the evolution of the temperature as heat is introduced only to one of the pistons. To this end, the system was modeled using finite element calculations. This dual capability proved to be very valuable for correction in the determination of the specific enthalpy. The performance of the SARC was evaluated by comparing the heat capacity results to those obtained by differential scanning calorimetry measurements using a commercial apparatus. The analyzed samples were zeolite, bauxite, hematite, bentonite, rice flour, corn flour, and potato starch.

Ferroelectric-Paraelectric Transition In A Membrane With Quenched-Induced δ-Phase Of PVDF.

The stabilization of δ-phase of poly(vinylidene fluoride) PVDF in a 14 µm-thickness ferroelectric membrane is achieved by a simple route based on the use of a dimethylformamide (DMF)/acetone solvent, in which the application of external electric field is not required. X-ray diffraction and calorimetric experiments on heating reveal that, at 154 °C, the original mixture between ferroelectric δ-phase and paraelectric α-phase transits to a system with only this latter phase in the crystalline fraction. A gradual and slight increment of amorphous fraction up to the melting at 161 °C is also observed. The existence of δ-phase is corroborated by the occurrence of a broad maximum around 154 °C in dielectric permittivity measurements, as well as the hysteresis loops observed at room temperature. These results suggest a wide thermal window for a stable δ-phase, between room temperature and 154 °C, a subsequent transition into α-phase and the corresponding melting at 161 °C. The broad dielectric maximum observed around 154 °C in dielectric and calorimetric measurements, can be associated with a diffuse ferroelectric-paraelectric transition.

Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland.

Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.

Novel RB1 gene constitutional mutations found in Polish patients with familial and/or bilateral retinoblastoma.

Retinoblastoma is the most common intraocular malignancy in children. It is estimated that 60 percent of cases are nonhereditary and unilateral, 15% are hereditary and unilateral, and 25 percent are hereditary and bilateral. Hereditary predisposition for retinoblastoma is caused by germline mutations in the RB1 gene and is transmitted in an autosomal dominant manner. Most of the reported mutations are unique to one family, but there are sites where mutations are recurrent. We have performed RB1 gene mutation analysis in eight patients with familial and/or bilateral retinoblastoma by DNA/RNA sequencing. Constitutional mutations were found in five out of eight patients. Three mutations were novel: g.IVS7+5G>A, g.156709T>A, and g.IVS21+1G>A (p.G203-E240del, p.Y659X, and p.I703-E737del).

Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma.

Synovial sarcoma (SS) is a mesenchymal neoplasm that typically shows epithelial differentiation. SS commonly metastasizes to lung and pleura, and has also been reported as the primary in these locations. The histologic distinction of SS from mesothelioma may be difficult because of the combination of epithelioid and spindle cells, potentially shared locations, and antigenic expression. In this study the authors examined 103 well-documented SSs including 41 biphasic, 44 monophasic, and 18 poorly differentiated SSs in comparison with 23 epithelioid and seven sarcomatous mesotheliomas. Most biphasic SSs (29 of 41, 71%) had fields or foci of calretinin-positive tumor cells. The spindle cell components were more often positive (55%), whereas 14% of tumors had positive epithelial cells. The monophasic and poorly differentiated SSs commonly had foci of calretinin-positive cells (in 52% and 56% of cases respectively). In comparison, all 23 epithelioid mesotheliomas (EM) were extensively calretinin positive and seven sarcomatoid mesotheliomas were variably calretinin positive. HBME-1 positivity was similarly detected in biphasic SS and EM (100% and 87% respectively). Among the other sarcomas, two of 15 malignant peripheral nerve sheath tumors were focally calretinin positive, whereas 16 epithelioid sarcomas, 20 leiomyosarcomas, 20 gastrointestinal stromal tumors, and 20 angiosarcomas were negative. Biphasic SSs differed from mesotheliomas by their more common BerEp4 positivity (90%) whereas EMs showed focal reactivity in 13% cases. Marked CD15 reactivity was rare in both. Wilms tumor protein-1 (WT1) was not detected in SS, but was present in 12 of 17 EMs. CD141 was rare in SS, limited to spindle cell components, whereas EMs typically showed prominent membrane staining in epithelial cells. Simple epithelial keratins were present in all epithelial cells of biphasic SS and mesothelioma (keratin 7[K7], K19), but were only focal in monophasic and poorly differentiated SS. Biphasic SSs were extensively K14 positive (89% of cases), whereas epithelial and sarcomatoid mesotheliomas typically showed only scattered positive cells. The potentially shared calretinin patterns in SS and mesothelioma require the use of other markers. The discriminating features include extensive BerEp4 positivity, rarity of CD141, and lack of WT1 in SS. Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful.

Two mosaic cases with nonfluorescent Y chromosome analysed with Y-specific DNA probes.

Two cases of a nonfluorescent Y (Ynf) chromosome were diagnosed: one in a male, the other in a female. Both had similar complex mosaic chromosome constitutions with a 45,X cell line. DNA studies were applied in both cases for verification of the cytogenetic diagnosis. The results on the two patients were compared with data obtained from seven healthy men (46,XY), three healthy women (46,XX), two females with 46,XY karyotype, and from cell lines with 49,XXXXY and 48,XXXX chromosome constitution. The highly repetitive Y-specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients. The highly repetitive Y-specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients. The suggestion that the Ynf chromosome originates from a dicentric Y chromosome cannot be accepted as a complete explanation of the phenomenon, as it probably involves more complex molecular alterations of the abnormal Y chromosome. The presence of Ynf is associated with the presence of a 45,X cell line more often than in cases of simple Y chromosome deletions with the breakpoint localized in or below the Y euchromatin/heterochromatin junction.

Mutations in the EDA gene in three unrelated families reveal no apparent correlation between phenotype and genotype in the patients with an X-linked anhidrotic ectodermal dysplasia.

Anhidrotic ectodermal dysplasia (EDA) is caused by mutations in the EDA gene encoding ectodysplasin A, a member of the TNF ligand superfamily involved in the communication between the cells. The structure of the EDA gene was investigated in three patients exhibiting clinical symptoms of EDA in an attempt to correlate the molecular findings with the phenotype of the patients. Genomic DNA was analyzed by single stranded conformation polymorphism (SSCP) followed by direct sequencing. In one of the patients, as well as in his heterozygous mother and sister, a single T insertion was evidenced in exon 3 between nucleotides 713 and 714 that changed Lys codon (AAA) into a termination codon TAA (Lys158Ter). In the other patient, A1321T transversion was demonstrated. The same mutation was found in his heterozygous mother and resulted in a change of Ileu360Asn that might generate an additional glycosylation site. In the third patient an A1285G transition was revealed. This mutation that originated de novo was localized in a region that is highly conserved in TNF ligand family and caused substitution of Ala349Thr. Localization of the mutations in the extracellular domain of ectodysplasin A suggested that the primary cause of EDA is a defect in communication between the cells responsible for the development of skin appendages. Despite a different character and localization of the mutations, no apparent correlation between phenotype and genotype of the patients was evidenced. Some differences in the patients' phenotype were observed.

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

Nonrandom secondary chromosome-aberrations in synovial sarcomas with t(x-18).

Thirty samples from 19 patients with synovial sarcoma were analyzed cytogenetically after short-term culturing. Thirteen samples were from primary tumors, 11 from local recurrences, and six from distant metastases. All samples showed the characteristic aberration t(X;18)(p11;q11) or variants thereof; 23 samples had additional numerical and/or structural changes. Including the present cases, chromosome aberrations have been reported in 74 synovial sarcomas, 50 of which have had secondary aberrations in addition to t(X;18). No secondary structural aberration was recurrent. The most common numerical changes were +7, +8, +12 (10 cases each), -3, +9, +21 (7 cases each), +2, -14, -17 (6 cases each), +4, -11, +15, and -22 (5 cases each). Unbalanced stuctural aberrations led to loss of 3p and 17p in six cases, each with loss of bands 3p21 and 17p13, respectively, in common. Most monosomies and trisomies seemed to occur at similar frequencies in primary, recurrent, and metastatic tumors. The only exceptions were +2, which was never seen in a primary tumor, and +8, which was never found in any metastatic lesion.

Cytogenetic and immunohistochemical profile of myxoid liposarcoma.

Cytogenetic and immunohistochemical studies were performed in nine myxoid liposarcomas. The tumor karyotype was determined after short-term culture of cells in vitro. Immunohistochemical studies were performed on frozen tissue in five cases and on paraffin-embedded tissue in three cases. Chromosomal analysis demonstrated a balanced translocation t(12;16) (q13;p11) as the sole abnormality in four cases. Two cases showed an association with other abnormalities. Three tumors showed variants of the t(12;16) translocation involving other chromosomes. In all cases studied, the 12q13 breakpoint was involved in rearrangements. In the majority of cases, immunohistochemical studies demonstrated vimentin (9 of 9) and S-100 protein (8 of 9). Strong focal expression of desmin was observed in two tumors. Weak focal expression was observed in three tumors. Two tumors, which were both desmin positive, showed focal expression of MSA and alpha-SMA. Strong expression of CD36 was present in all four cases that were studied for this marker. CD34 was negative in tumor cells, but it highlighted an intricate capillary network in the tumor. Close relationship between the tumor cells and pericapillary pericytes was demonstrated with CD34 and alpha-SMA strains. The authors conclude that myxoid liposarcoma is characterized by a specific chromosomal rearrangement. Its immunohistochemical profile is wider than previously believed, including expression of muscle markers.

Patterns of keratin polypeptides in 110 biphasic, monophasic, and poorly differentiated synovial sarcomas.

Synovial sarcoma is a mesenchymal neoplasm of unknown histogenesis that shows various degrees of epithelial differentiation. It is known to contain simple epithelial keratins, and the possibility of complex epithelial keratin expression has been suggested. In this study, we immunohistochemically examined 110 well-documented synovial sarcomas including 44 biphasic, 48 monophasic, and 18 poorly differentiated (undifferentiated, highly mitotically active) tumors for 11 different keratin (K) polypeptides of the Moll catalogue. The epithelia of biphasic synovial sarcomas showed consistent, extensive reactivity for K7, K8, K14, K18, and K19. Other keratins seen in the epithelia of biphasic tumors included K17 (variable, in 77%), K13 (25%), K16 (23%), and K6 (24%) in the minority of biphasic tumors, predominantly in stratified-appearing epithelia. K10 was detected only focally in one case that showed keratinizing squamous differentiation. Focal expression of K20 was seen in 27% of cases. Monophasic synovial sarcomas had a more limited keratin repertory. Simple epithelial keratin positivity was detected, usually focally for K7 (79%), K19 (60%), K8 (45%), and K18 (46%). Two cases showed more extensive keratin positivity in the spindle cells. The monophasic tumors showed limited positivity for complex epithelial keratins: K14 (28%) and K17 (10%). K20 was detected focally in 6% of the monophasic tumors; other keratins were not detected. The poorly differentiated synovial sarcomas showed limited simple epithelial keratin reactivity, usually limited to scattered cells: K19 (61%), K7 (50%), K18 (47%), K8 (33%), but five cases showed more extensive positivity. Complex epithelial keratins were scant: K14 in one case and K17 in two cases. The immunoreactivity of capillary endothelia seen for K7 and K18 (but not for K8 and K19 with the antibodies used) is a potential diagnostic pitfall, and may cause overdiagnosis of synovial sarcoma if not properly recognized. In summary, we show complex patterns of keratins in synovial sarcoma, especially in the biphasic tumors. Such patterns establish a baseline in differential diagnostic considerations, and give an insight into the complex epithelial differentiation of this enigmatic mesenchymal tumor.