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Biomedical subjects

B Czerniak

Publications and source records attributed to B Czerniak.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bone cancers.

BACKGROUND: Frequency distribution data for primary bone sarcomas have long been used to provide clues to the diagnosis of bone cancers after their identification in radiographs. Age and skeletal site are often helpful, in addition to specific radiographic features, in narrowing down the probable histologic categories of bone neoplasms before biopsy. METHODS: Data on 2627 histologically confirmed primary malignant tumors of bone, as collected by the SEER program during the period 1973-1987, were analyzed by age, sex, race, and anatomical site. RESULTS: Osteosarcoma was the most frequently diagnosed primary sarcoma of bone (35.1%), followed by chondrosarcoma (25.8%), Ewing's sarcoma (16.0%), chordoma (8.4%), and malignant fibrous histiocytoma, including fibrosarcoma (5.6%). The most frequently diagnosed sarcoma of bone in persons younger than age 20 was osteosarcoma, followed by Ewing's sarcoma. Chondrosarcoma was the most frequently diagnosed bone tumor in the population older than age 50. The overall 5-year relative survival rates were as follows: osteosarcoma, 41.0%; chondrosarcoma, 72.7%; Ewing's sarcoma, 41.2%; chordoma, 63.8%; and malignant fibrous histiocytoma, 42.9%. There was an improvement in the survival rates during the period 1973-1987 for patients with chordoma and for white female patients with Ewing's sarcoma. Ewing's sarcoma and chordoma occurred almost exclusively in the white population. CONCLUSIONS: SEER data provide a unique opportunity to evaluate the incidence and survival rates of bone sarcomas, which are uncommon but highly lethal tumors. The findings from this analysis provide information useful in the diagnosis of these cancers.

Adolescent↗
PubMed1995

p53 expression and DNA ploidy of cartilage lesions.

The aim of this study was to investigate the expression of a tumor suppressor gene (p53) in cartilage lesions of bone and its relationship to their histological grade and DNA ploidy. An immunohistochemical assay for p53 and Feulgen-stained DNA preparations was subjected to computerized image analysis. Enchondromas, synovial chondromatosis, and low grade (grade I and II) chondrosarcomas were diploid. High grade (grade III) chondrosarcomas and high grade sarcomatous components of dedifferentiated chondrosarcomas were aneuploid. Well differentiated cartilaginous components of dedifferentiated chondrosarcomas were diploid. Microscopic examination showed weak focal positivity for p53 in one of 10 enchondromas one of six examples of synovial chondromatosis, and three of four low grade (grade I and II) chondrosarcomas. All three high grade (grade III) chondrosarcomas were strongly positive for p53. The high grade sarcomatous component of all four dedifferentiated chondrosarcomas was strongly positive for p53, whereas only focal weak positivity was noted in the well differentiated cartilaginous areas. These results were confirmed by quantitative computer-assisted image analysis, which showed that high grade aneuploid cartilage tumors demonstrated strikingly higher levels of p53 than did diploid low grade malignant tumors or benign cartilage lesions.

Adult↗
PubMed1995

Nodular spindle-cell vascular transformation of lymph nodes. A benign process occurring predominantly in retroperitoneal lymph nodes draining carcinomas that can simulate Kaposi's sarcoma or metastatic tumor.

We describe a vasoproliferative nodular spindle-cell lesion representing a variant of vascular transformation of lymph-node sinuses and designated a nodular spindle-cell vascular transformation of lymph nodes. The lesion is most frequently identified in retroperitoneal lymph nodes excised in association with radical nephrectomies for renal cell carcinoma, but it can also be present in association with other malignant tumors. Occasionally it is seen in superficial lymph nodes in patients with no history of malignant neoplasms. This lesion can be confused with Kaposi's sarcoma or with a metastatic sarcomatoid carcinoma because of its spindle-cell composition, cellularity, occasional high mitotic activity, and frequent occurrence in the regional lymphatic drainage of a known malignancy.

Adult↗
PubMed1992

Asymmetric distribution of oncogene products at mitosis.

Computer-assisted image analysis was used to demonstrate in exponentially proliferating human tumor cells the uneven postmitotic apportionment of several oncogene-encoded proteins (ras p21; erbB-2 p185; fos p55; myc p62). This observation may provide the explanation for the high degree of heterogeneity of postmitotic cells and the asynchrony in cell cycle traverse of cultured cells.

Cell Compartmentation↗
PubMed1992

Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas.

This report concerns the study of Ha-ras gene mutations and ras p21 expression in primary tumors of the urinary bladder. Polymerase chain reaction-based techniques and computerized image analysis were used. The data obtained were related to tumor grade, DNA ploidy, and tumor invasion. A point mutation (G-->T) at Ha-ras codon 12 was found in 30 of 67 tumors. The mutation frequency was greater in grade III (65%) than in grade II (44%) tumors; no mutations were observed in grade I tumors. The mutation was observed more often in aneuploid (58%) than in diploid (28%) tumors. No other substitution at codon 12 was seen and no codon 61 mutation was detected. The tumors were also tested for the A-->G mutation at position 2719 of Ha-ras intron D. Concurrent codon 12 and intron D mutations were identified in seven high-grade aneuploid tumors; six were invasive. The levels of the ras gene product p21 were approximately 10 times higher in tumors with intron D mutation than in those without. These findings confirm on human bladder tumors the observations of the effect of synchronous exon-intron mutations reported on the bladder cancer cell line T24. Our results are the first demonstration of Ha-ras intron D alterations in human tumor tissues and suggest that concurrent mutations at codon 12 and intron D of this gene within the same tumor may contribute to the aggressive behavior of human bladder carcinomas.

Adult↗
PubMed1991

Protein expression in relation to the cell cycle of exponentially growing human prostatic epithelial cells.

This report concerns the study of the relationship between protein expression and the cell cycle in exponentially proliferating benign and malignant human prostate epithelial cells in short-term cultures. Multiparameter flow cytometric measurements were performed to correlate the expression of prostate-specific acid phosphatase, epithelial membrane antigen and epitectin with cell cycle progression. The expression of the three proteins was heterogeneous in G1 cells. The early post-mitotic cells exhibited the lowest levels when compared with late G1 cells, wherein the expression was many times greater. There was no further increase as the cells progressed through S and G2 + M. These findings, corroborating prior observations in other systems, suggest the possibility that the levels of the proteins studied increase during the G1 phase of the cell cycle and drop during or immediately after cytokinesis. As an alternate explanation, the heterogeneity of protein expression characteristic of G1 cells may be due, at least in part, to an asymmetric apportionment of cell constituents at mitosis.

Acid Phosphatase↗
PubMed1990

Quantitation of oncogene products by computer-assisted image analysis and flow cytometry.

The use of antibodies permits the study of oncogene product expression in cells and tissues. However, quantitation of the levels of expression in immunohistochemical preparations is beset by difficulties, and the available scoring system provide semiquantitative data at best. Here we describe the use of computer-assisted image analysis for determination of oncoprotein levels in a model system and compare the results with those generated by flow cytometric analysis. The oncogene products measured are located in the nucleus (c-myc p62 and c-fos p55), the inner surface of the membrane (c-ras p21), and both sides of the membrane (c-erbB-2 p185). In each instance, both analytic modalities yielded concordant results. Our data indicate that computer-assisted image analysis is a useful tool for quantitating cell components in immunohistochemical preparations.

Breast Neoplasms↗
PubMed1989

Morphologic diversity of long bone adamantinoma. The concept of differentiated (regressing) adamantinoma and its relationship to osteofibrous dysplasia.

A review of the clinical, radiologic, and histologic features of 25 cases of long bone adamantinoma is presented. To answer some questions concerning the nature of these tumors, relevant tissue markers were analyzed in seven cases using immunohistochemical assays. This study confirmed the epithelial nature of long bone adamantinomas irrespective of their wide-ranging morphologic patterns that can mimic tumors of various origin. On the basis of distinct radiologic, histologic, and immunohistochemical patterns, a new type of adamantinoma termed "differentiated adamantinoma" could be distinguished from the classic long bone adamantinomas. The diagnostic features characteristic of the differentiated adamantinoma include: patient age (first two decades), intracortical location of the entire lesion, uniform predominance of an osteofibrous dysplasia-like pattern, and scattered positivity of epithelial elements for cytokeratin. We postulate that the predominance of an osteofibrous dysplasia-like pattern in differentiated adamantinoma is the result of a secondary reparative process overgrowing matured and regressing tumor tissue. It is possible that this process may lead to the total elimination of recognizable tumor cells from the lesion. Therefore, osteofibrous dysplasia (ossifying fibroma) of long bones, which has a similar anatomic location, age distribution, and radiologic appearance as differentiated adamantinoma, may, in some cases, represent the evolution of an underlying adamantinoma. Our analysis suggests that long bone adamantinoma could be another member of the unique family of tumors that may regress spontaneously.

Adolescent↗
PubMed1989

Expression of ras oncogene p21 protein in early gastric carcinoma and adjacent gastric epithelia.

The expression of the ras gene product p21 in normal gastric mucosa, early gastric carcinoma of diffuse (gastric) and intestinal types, and in adjacent mucosal abnormalities is reported. The analysis was performed on paraffin sections by an immunohistochemical assay using the mouse monoclonal antibody RAP-5 and the rat monoclonal antibody Y13-259. Expression of ras p21 was assessed by staining intensity and percentage of positively stained cells. In comparison to normal gastric mucosa of non-cancer patients, p21 was overexpressed in nearly all early carcinomas of both types and in the dysplastic and/or metaplastic mucosal alterations accompanying intestinal type of gastric cancer. Increased p21 expression was also observed in the normal-appearing mucosa adjacent to early carcinomas of diffuse type, but not in the morphologically normal gastric epithelium adjacent to the intestinal type. The results of this investigation suggest that ras p21 overexpression may be related to early events of human gastric carcinogenesis. The study supports the notion of different pathways in the development of diffuse (gastric) and intestinal types of gastric carcinomas.

Adenocarcinoma↗
PubMed1989

Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas.

The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha-ras, Ki-ras, and N-ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.

Breast Neoplasms↗
PubMed1989

Flow cytometric measurements of DNA and other cell components in human tumors: a critical appraisal.

Fundamental principles of flow cytometry with emphasis on DNA measurements and cell cycle analysis in human cells and tissues are summarized. Some of the pitfalls of cell preparation techniques and histogram interpretation are discussed at length. While consensus has been reached for some organs and tumors that DNA quantitation by flow cytometry (or image cytometry) may be of prognostic value, for most cancers studied to date the information remains incomplete. Thoroughly lacking are well-structured prospective studies because retrospective studies, while suggestive, may not necessarily be of the same value. Potential usefulness of other tumor markers is briefly discussed. Many fundamental questions concerning definitions of "diploid" and "aneuploid" tumors have not been satisfactorily settled. While the goal of "objective measurements" is worthy of further pursuit, the interpretation of results is often highly subjective. The biologic reasons for behavioral differences between diploid and aneuploid tumors are still totally obscure.

Cell Cycle↗
PubMed1987

ras oncogene p21 as a tumor marker in the cytodiagnosis of gastric and colonic carcinomas.

This study was undertaken to determine whether the expression of ras oncogene product p21 can be used as a tumor cell marker of gastric and colonic carcinoma in brush smears. To detect p21 an immunocytochemical assay with RAP-5 monoclonal antibody was used. Benign epithelial gastric cells obtained from normal gastric mucosa or benign gastric lesions reacted negatively in 12 out of 13 cases. Similarly, benign epithelial colonic cells from normal colon or benign colonic lesions were negative for p21 in nine out of ten cases. Weakly positive reaction, confined to a few cell clusters only, was observed in one smear of a benign gastric ulcer and one smear of chronic ulcerative colitis. All 20 smears from colonic carcinoma and all 20 smears of gastric carcinoma contained cells that stained positively for p21, and the degree of tumor differentiation had no impact on the staining pattern. The results recorded in this study show that the immunocytochemical assay for the ras oncogene product may prove to represent a new tool for the cytodiagnosis of gastric and colonic carcinomas.

Antibodies, Monoclonal↗
PubMed1987

Modification of Ha-ras oncogene p21 expression and cell cycle progression in the human colonic cancer cell line HT-29.

Multiparameter flow cytometric measurements of the Ha-ras oncogene product, Ha-p21, versus DNA content were used to study the effect of prednisolone, sodium butyrate, and hyperosmolality on the expression of this gene during the cell cycle of HT-29, a human colonic carcinoma cell line. In control cells the expression of Ha-p21 was cell cycle dependent; it increased during G1 and remained approximately constant as cells traversed the S- and G2 + M phases. Two compartments of G1 cells, one expressing low (G1A) and the other (G1B) high levels of Ha-p21 could be identified. Cells grown with prednisolone (1.4-2.1 microM) expressed higher Ha-p21 levels than controls. Cell cycle analysis revealed that this effect was accompanied by a change in the distribution of cells in G1 phase: whereas the proportion of cells in G1A was reduced, that of cells in G1B was increased. The steroid had no detectable effect on cells in S and G2 + M. By contrast, sodium butyrate and hyperosmolality caused a marked decrease in Ha-p21 content. This reduction was not accompanied by any modification of the proportion of cells in the cell cycle compartments. These results would suggest that Ha-p21 is not likely to be a primary regulator of cell cycle progression in HT-29 cells.

Butyrates↗
PubMed1987

DNA distribution patterns in early gastric carcinomas. A Feulgen cytometric study of gastric brush smears.

DNA distribution patterns were studied by cytophotometry in 20 Feulgen-stained brush smears of early gastric carcinomas. Two different DNA distribution patterns, classified as predominantly diploid and aneuploid, were correlated with histologic data. Six of seven carcinomas of diffuse type were predominantly diploid. By contrast, 11 of 13 intestinal type carcinomas were aneuploid and two were diploid. Since the DNA distribution patterns recorded in this study were previously observed in advanced gastric carcinomas, this would suggest that the basic genetic make-up of the tumors does not change with tumor progression.

Adult↗
PubMed1987

Expression of Ha-ras oncogene p21 protein in relation to the cell cycle of cultured human tumor cells.

It has been postulated that the expression of the product (p21) encoded by the ras genes may have a role in cell cycle events. Simultaneous multiparameter flow cytometry was used to measure the p21 content in relation to the cell cycle of several cancer cell lines of human origin. These studies revealed that p21 levels rise during the G1 phase of the cycle and remain approximately constant as cells traverse the S and G2 + M phases. The threshold level of p21 expression of S phase cells was used to divide the G1 cell population into cells with low (G1A) and high (G1B) p21 content. The p21 levels of G1B cells were approximately ten times higher than those of G1A cells. The validity of this subdivision was confirmed by synchronous measurements of RNA content and p21. Cells with low RNA content, hence in early part of G1 phase of the cell cycle, expressed low levels of p21, and cells with higher RNA content expressed higher levels of p21. These observations suggest that the levels of p21 are much lower at the onset of the cell cycle than at its end; hence a drop in p21 expression is likely to occur during or immediately after mitotic division.

Cell Cycle↗