Synovial sarcoma (SS) is characterized by the t(X;18)(p11.2;q11.2) chromosomal translocation, which results in generating either
SYT-SSX1,
SYT-SSX2 or, infrequently,
SYT-SSX4 fusion gene. The ratio ...of
SYT-SSX1:
SYT-SSX2 fusions is close to 2:1 in the majority of studies, and
SYT-SSX2 fusion has been only rarely observed in biphasic SS. In the present study, we compared two series of patients with SS, Slovenian (37 cases) and Dutch (14 cases), with respect to clinical, pathological and molecular findings. The two groups did not differ with regard to clinicopathological features. Whereas the frequency of different
SYT-SSX fusions in the Dutch group was similar to that reported in the literature, we found an unexpectedly high number of tumors with
SYT-SSX2 fusion in the Slovenian group. The ratio of
SYT-SSX1:
SYT-SSX2 fusion was 7:18 for monophasic and 2:7 for biphasic tumors in the Slovenian group. This distribution differs significantly from that observed in the Dutch group in the present study (
P = 0.041) as well as from data reported in the recent large multi-institutional study on 243 patients (
P = 0.0001). Our findings indicate possible geographical differences in the frequency of two
SYT-SSX fusion transcripts in patients with synovial sarcoma.
To test the discriminatory capability of nuclear features in the subclassification of rhabdomyosarcoma (RMS) and especially to differentiate embryonal from alveolar RMS.
The study included 42 ...patients with RMS. We performed the analysis on Feulgen-stained filtrates of cell suspensions prepared from deparaffinized tissue sections. Image analysis was performed by an automated, high-resolution image cytometer on at least 200 nuclear images. Photometric, morphometric and nuclear texture features were analyzed. Probability density distributions were calculated for each nuclear feature of individual RMS subgroups and compared in order to detect possible differences.
There were significant differences between embryonal and alveolar RMS in five nuclear features: DNA index, sphericity, elongation, low_DNA_area and fractall_area. We were able to differentiate between the two main RMS subgroups in 82% of cases on the basis of either sphericity or elongation alone, while the power of differentiation for texture features was 72-79%.
Differentiation between embryonal and alveolar RMS using one nuclear feature is not an important adjunct to light microscopy. However, the possibility of using a combination of nuclear features would probably increase the discriminatory ability.
We have identified a novel germline nonsense mutation in exon 15 of the human mismatch repair gene (MMR) <hMLH1< which is mutated in patients with hereditary nonpolyposis colorectal cancer (HNPCC). ...The substitution of thymine for cytosine at nucleotide position 1684 results in a termination codon at amino acid position 562.
The aim of this study was to investigate the role of P-glycoprotein (P-gp) in the adrenal gland. It has been presumed that P-gp, rather than being involved in physiological cortisol secretion, plays ...a role in protecting the adrenacortical cells from xenobiotics. To explore this a study was performed on perfused bovine adrenal glands. Individual experimental groups were perfused with either a selective P-gp blocker (valspodar) alone, with a xenobiotic (mitotane or doxorubicin) alone or with both valspodar and a xenobiotic. The cumulative amounts of cortisol secreted in each individual group were calculated and the two-sample t-test was used to compare the mean values of cumulative amounts. The mean value of cortisol secreted from the group of adrenals perfused with the P-gp blocker was not significantly different from that of the control group. Treatment with either mitotane or doxorubicin decreased the amount of cortisol secreted but not significantly when compared to the amount of cortisol secreted in basal conditions. However, treatment with the P-gp blocker valspodar in addition to either mitotane or doxorubicin significantly decreased cortisol secreted compared to the amount of cortisol secreted by the glands treated with either mitotane (p=0.009) or doxorubicin (p=0.017) alone. The regressive changes discovered in all experimental groups were most prominent when valspodar was used with either mitotane or doxorubicin. We found that P-gp blockade increases by xenobiotic (mitotane and doxorubicin)-induced damage of adrenocortical cells, which points to a role of P-gp in the protection of adrenal gland from xenobiotics.
The purpose of this study was to determine estrogen receptor (ER) and progesterone receptor (PR) expression assessed by dextran-coated charcoal method (DCC) and standardized immunohistochemical ...method (IHC) in a prospective series of 557 primary breast carcinomas, to assess the concordance between the two assays, and to evaluate the association between hormone receptor expression and various clinicopathological parameters.
For ER, results of both methods were in agreement in 73.6% of the cases (277 positive, 133 negative), 74 tumors (13.3%) where IHC+/DCC- and 73 (13.1%) were IHC-/DCC+. For PR, concordant results were observed in 72.7% of the cases (201 positive and 204 negative), 127 tumors (22.8%) were IHC+/DCC- and 25 (4.5%) were IHC /DCC+.
Irrespective of the method used, ER and PR positivity showed a strong negative association with tumor grade. ER+ tumors were significantly more common among older patients. With IHC, PR+cases were more common among tumors of lobular and mucinous type and among node positive tumors.
The only parameter that was related to the concordance rate of ER determination by the DCC and IHC method was the age of the patients, with agreement being significantly lower in the group of patients younger than 50 years. On the other hand, discordant PR determination was more often observed in tumors of lower grade, node positive tumors and in tumors of lobular and mucinous type.
To analyze cytomorphologic characteristics of hepatoblastoma (HB) and evaluate the feasibility of recognizing its histologic subtypes in smears.
Fine needle aspirates from 14 primary and 1 metastatic ...HB were reexamined. The diagnosis of HB was confirmed by tissue examination (10 cases) and by clinical and laboratory findings alone (5 cases).
In 12 samples, neoplastic cells resembled immature hepatocytes but were smaller and had a higher nuclear/cytoplasmic ratio. In nine of these smears the cells were rather uniform, while the other three presented with moderate pleomorphism. The cells were arranged in three-dimensional clusters, loose sheets, cords, rosettelike structures and occasional pseudopapillae and were dispersed.
With knowledge of the cellular features and architectural patterns of HB, a reliable diagnosis could be obtained in 12/15 cases without the use of special techniques. In the remaining three aspirates the tumor cell population partly or entirely differed from normal hepatocytes, requiring ancillary techniques for proper diagnosis. On reexamination of the 10 cases with tissue diagnoses, 4/6 mixed HBs could be correctly subtyped, whereas the distinction between embryonal and fetal cells in four cases of epithelial HB seemed questionable.
Anti-tumor effectiveness of tumor necrosis factor (TNF)-alpha applied peritumorally was assessed in combination with local electrotherapy on subcutaneous SA-1 tumors in mice. TNF and electrotherapy ...each induced significant tumor growth delay. In combined treatment using TNF and electrotherapy, a synergistic anti-tumor effect was observed, regardless of whether TNF was injected before or after electrotherapy. An extra anti-tumor effect was achieved when TNF in the same total dose (2 x 10(5) U) was split into a priming dose (0.5 x 10(5) U) 1 h before electrotherapy and the other (1.5 x 10(5) U) 24 h thereafter. As the result of this therapeutic combination survival rate of the animals was 40%. No animal survived more than 50 days in groups subjected to TNF or electrotherapy treatment alone. Combined treatment with TNF and electrotherapy induced massive tumor destruction, confirmed by histological examination 2 days after the treatment. The results indicate that TNF and electrotherapy interact and that they can be effective in control of local tumor growth.
Proteolytic enzymes have been proposed as new biological prognostic indicators to facilitate decisions about treatment of breast cancer patients following surgery. We reported earlier that the ...activities of cysteine proteinases (CP), cathepsin (Cat) B and cathepsin (Cat) L and the expression of stefin A might be associated with breast tumor progression and prognosis. Here, the protein concentrations of Cats D, B and L and stefin A have been measured in a series of 60 matched pairs of breast tumours and control adjacent tissues, using ELISAs developed in our laboratory. Median tumor concentrations of Cat D (47 pm/mg), Cat B (222 ng/mg) and Cat L (88 ng/mg) were significantly (p<0.0005) increased by 7 fold, 27 fold and 6 fold, respectively. Much greater increases in the activities of Cat B (63 fold) and of Cat L (274 fold) were found, indicating activation of proCat B and proCat L and/or to a decrease in specific endogenous cystatins. However, the 1.6-fold decreased (p<0.0001) levels of inhibition by cystatins could not be entirely responsible for more than 100-fold increased ratio of CP:cystatins activity. Moreover, stefin A was either increased or decreased in tumor samples, resulting in a 1.4-fold median increase in tumors. Comparing the biological parameters with the established histo-pathological prognosticators, we found that the increased protein concentration of Cat B was associated with lymph node involvement (p<0.009) and higher stage (p<0.003), and both Cat B and Cat L activities were more increased in high grade tumours (p<0.05). Survival analysis revealed that stefin A was the most significant prognostic factor for disease-free (p<0.008) and overall survival (p<0.02), followed by increased Cat B activity and protein concentration. Cat L was of borderline significance while Cat D was not significant for prognosis. We conclude that enhanced activation of CP, due partially to an imbalance between cysteine proteinases and inhibitors is linked to the progression of breast cancer. Larger sample size is needed to confirm the prognostic significance of stefin A, Cat B and Cat L.
Microsatellite instability (MSI) analysis was performed using a “reference panel” of microsatellite markers in 345 unselected primary colorectal cancers (CRC). Thirty-five (10%) tumors were ...classified as high MSI (MSI-H). We identified 6 (17%) MSI-H tumors with germline mutations in mismatch repair (MMR) genes (tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome) and 29 (83%) MSI-H tumors without germline MMR mutations (sporadic MSI-H tumors). Hypermethylation of the
hMLH1 promoter was found in 26/29 (90%) sporadic MSI-H tumors but only in 1/6 (17%) HNPCC tumors (
P<.001). Somatic alterations were identified in both MMR genes in HNPCC tumors but mainly in the
hMSH2 gene in sporadic MSI-H tumors. LOH at MMR loci was detected in 3/6 (50%) HNPCC tumors and in 4/26 (15%) informative sporadic MSI-H tumors. These results together indicate different mode of inactivation of MMR genes in sporadic MSI-H tumors versus MSI-H tumors in HNPCC patients. We therefore propose that MSI analysis of newly diagnosed primary CRC followed by methylation analysis of
hMLH1 promoter in MSI-H tumors and mutational analysis of MMR genes in MSI-H tumors lacking
hMLH1 promoter methylation might be an efficient molecular genetic approach for HNPCC screening.
