Two hundred thirty randomly collected primary colorectal tumors were initially screened for microsatellite instability (MSI) with three highly informative microsatellite markers (BAT26, D2S123 and ...D5S346). Forty one (17.8%) tumors showed alterations in at least one marker. In further MSI analysis of these 41 MSI tumors with additional 9 markers, 21 tumors (9.6% of 230 analyzed) exhibited MSI at more than 40% and the rest 20 (8.7% of 230 analyzed) tumors exhibited MSI at 8%-20% tested markers. These results support classification of MSI tumors into high MSI tumors (more than 40% unstable loci) and low MSI tumors (less than 20% unstable loci). Based on our results the combination of BAT26 and two out of four other highly informative markers (D2S123, D5S346, BAT25 or BAT40) is recommended for rapid and reliable assessment of high MSI tumors.
Two brothers with multicentric infantile myofibromatosis (IM) are reported. In both, tumors were present at birth; the tumors regressed spontaneously, but new lesions developed throughout the ...follow‐up periods of 15 and 8 years. Immunohistochemically, the nodules were found to be positive for vimentin and actin, but negative for desmin and S‐100 protein; these findings support the myofibroblastic nature of IM. A literature review revealed nine additional families with IM in more than one family member. Although the occurrence of IM in eight sets of siblings, with consanguinity in two of them, favors an autosomal recessive mode of inheritance, the disorder also has been well documented in half‐sisters and in successive generations, which makes autosomal dominant inheritance a more plausible explanation.
In the study of 50 matched pairs of breast carcinoma and normal breast tissue, the activities of cysteine proteinases (CPs), cathepsin (Cat) B and Cat L in tumors were increased on average by ...18.5-fold and 52.5-fold respectively. The differences in activity of cysteine proteinase inhibitors (CPIs) between tumor and control breast tissues was also observed: in approximately two thirds of carcinomas, lowered CPI activity was measured (group-I patients), while similar or higher tumor CPI activity was measured in the remaining samples (group-II patients). Relative increases in specific activity of Cat B and Cat L in group I were significantly higher than in group II. In group I more patients with histopathological tumor grade III and negative estrogen (ER) and progesterone receptor (PR) levels were found, but the metastatic involvement of regional lymph nodes was similar in both groups. A 2-year follow-up study showed a significant inverse correlation between disease-free survival and increased Cat L activity, but the differences in group I and group II patients were not significant in this short time interval. In 20 matched pairs of breast carcinoma and normal breast tissue, the mean activity of Cat D was 5.8-fold higher in tumors compared with controls. The hypothesis that elevated Cat D activity increased CP activity and/or lowered tumor CPI activity due to post-translational proteolytic modification appeared less likely, since no correlations between corresponding activities were observed. We suggested that lowered CPI might rather reflect changes in transcription of intracellular CPIs, the stefins. Immunoassay and Northern blot analysis showed that the average value of stefin A protein and mRNA content respectively in the majority of investigated breast carcinoma samples were lowered, suggesting the possible value of stefin A in diagnosis and/or prognosis of the disease.
Cysteine, serine and metalloproteinases and their respective inhibitors are involved in tumor cell invasion and may have prognostic value for the outcome of malignant disease. The aim of the study ...was to compare the expression of new potential biological tumor markers, the lysosomal cysteine proteinases and their endogenous inhibitors, with that of the serine proteinases and their inhibitors in breast cancinoma and to relate their levels to the clinicopathological factors of the disease. Enzyme-linked immunosorbent assays (ELISAs) were used to measure cysteine cathepsin B (CatB) and cathepsin L (CatL) and their inhibitors, stefin A (StA) and stefin B (StB), together with urokinase (u-PA) and plasminogen activator inhibitor-1 (PAI-1), in 150 cytosols of primary invasive breast carcinoma. A good correlation was found between the levels of the two cysteine proteinases but only a moderate one between those of the cysteine and serine proteinases. u-PA and PAI-1 levels correlated positively with histological grade and negatively with estrogen receptor (ER) status. PAI-1 correlated with most clinicopathological factors that indicate the progression of the disease, while cathepsins and stefins were independent of these factors. In the total group of patients, high u-PA and PAI-1 and low StB levels correlated significantly with shorter disease-free survival (DFS), while CatB, CatL and StA did not. In lymph node negative patients, high CatB and CatL were also associated with shorter DFS, while u-PA remained the most significant of all these biological markers. In conclusion, this retrospective study showed u-PA to be of better prognostic relevance than the cysteine proteinases, though CatB and CatL were relevant for prognosis in lymph node negative breast cancer patients.
In a retrospective study of 60 spindle-cell sarcomas of peripheral soft tissues, we evaluated the extent of immunostaining with antibodies against Ki-67, proliferating cell nuclear antigen, and p53 ...protein and flow-cytometric DNA ploidy, their relation to tumor location, depth, histologic type, size, mitotic rate, and extent of tumor necrosis, as well as their influence on survival. Although Ki-67-labeled nuclei were detected in only 41 tumors (68%) and their number varied from 1 to 50%, proliferating cell nuclear antigen immunoreactive nuclei were found in each tumor, with their number ranging from 20 to 99%. p53 Protein was found in 26 cases (43%), and its labeling ranged from 1 to 80%. Although Ki-67 labeling significantly correlated with mitotic rate, no correlation could be found between proliferating cell nuclear antigen or p53 labeling and any other variables studied. Thirty-eight percent of the tumors were diploid, and 64% were aneuploid. Factors that significantly reduced survival in univariate analysis were increasing size and depth of the tumor, the presence of necrosis, the National Cancer Institute grade, and a tetraploid/hypertetraploid DNA pattern. In multivariate analysis of 49 cases with complete information, only DNA ploidy pattern, tumor size, and tumor necrosis retained their independent prognostic significance.
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.
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