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Biomedical subjects

B Czerniak

Publications and source records attributed to B Czerniak.

At least 19 recordsLinked to original sources
PubMed1996

Apoptosis and downstaging after preoperative radiotherapy for muscle-invasive bladder cancer.

PURPOSE: To determine the relationship between pretreatment apoptosis levels and clinical-to-pathologic downstaging resulting from preoperative radiotherapy. METHODS AND MATERIALS: Between 1960-1983, 338 patients were dispositioned to receive preoperative radiotherapy 4-6 weeks prior to radical cystectomy for muscle-invasive transitional cell carcinoma of the bladder. Of these, adequate hematoxylin and eosin stained tissue sections for morphologic analysis of apoptosis were available in 158 patients. These patients were treated to a median dose of 50 Gy at 2 Gy per fraction. Median follow-up was 90 months. The apoptotic index (AI) was calculated from the ratio of the number of apoptotic cells divided by the total counted and multiplied by 100. A minimum of 500 cells were counted from each patient. RESULTS: The average AI for the whole group (n = 158) was 2.0 +/- 1.3 (+/- SD), with a median of 1.8. The association of AI to clinical stage was significant with AI averages of 1.8 for Stage T2 (n = 56), 1.9 for T3a (n = 51), and 2.4 for T3b (p = 0.038, Kendall Correlation). The relationship of AI to radiotherapy response also was significant with an average of 2.2 for those who were downstaged (n = 103), 1.9 for those in whom the stage remained unchanged (n = 20), and 1.7 for those who were upstaged (n = 35, p = 0.054, Kendall Correlation). The other significant correlations with AI were for the factors, grade, mitotic index, number of tumors, and gender. The AI was then categorized into three groups ( < or = 1, > 1, and < or = 3, and > 3) to examine the prognostic significance of this parameter. The distributions of patients by clinical stage, grade, mitotic index, number of tumors, radiotherapy response, and hemoglobin level were significantly associated with AI using this grouping. When the analysis of the distribution of patients by radiation response and AI was segregated by stage, a significant correlation was observed only for those with Stage T3b disease (p = 0.006); 93% of T3b patients with an AI > 3 were downstaged, while in 7% the stage remained unchanged and none were upstaged. The relationship of AI to 5-year actuarial patient outcome was investigated using several end points and although no significant correlations were observed, a trend was seen for improved survival when AI was > 3 (71% vs. 41%, p = 0.09) for Stage T3b patients. CONCLUSION: The AI correlated most strongly with radiotherapy response for patients with clinical stage T3b disease, the one subgroup of patients wherein preoperative radiotherapy is likely to be of the most benefit. Further investigation of pretreatment apoptosis levels as a marker of anticancer response is needed, especially for patients treated with chemotherapy and radiotherapy with the goal of bladder preservation.

Aged↗
PubMed1996

Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy.

OBJECTIVES: The relationship of p53 mutations as analyzed immunohistochemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cystectomy. METHODS: Adequate formalin-fixed paraffin-embedded archival tissue for the immunohistochemical staining of p53 using antibody DO1 was obtained in 109 patients. The median follow-up for those living was 91 months. RESULTS: Overall, p53 staining was positive in 56% of the cases, with 60% positive in Stage T2 (n = 48), 42% in Stage T3a (n = 31), and 63% in Stage T3b (n = 30). Overexpression of p53 did not correlate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were seen when these analyses were limited to patients with clinical Stage T3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55% and 100%, respectively, for distant metastasis freedom (P = 0.01), 51% and 91% for disease freedom (P = 0.04), and 32% and 91% for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining and other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease. CONCLUSIONS: The prognostic value of p53 immunostaining rested with Stage T3b patients. Although no correlations were found with radiation response, p53 positivity in this subgroup was associated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggressive local treatment (that is, preoperative radiotherapy and cystectomy) is sufficient, whereas p53 positivity would indicate that multiagent chemotherapy is required because of the increased risk of distant metastasis.

Carcinoma, Transitional Cell↗
PubMed1995

p53 expression in dedifferentiated chondrosarcoma.

BACKGROUND: p53 acts as a tumor suppressor gene because of to its negative control of the cell cycle and its central role in programmed cell death. It frequently is mutated, as observed in a variety of human neoplasms. The mutations inhibit tumor-suppressor activities of p53, which may gain a new function of tumor promotion. In this study, p53 was investigated in various components of dedifferentiated chondrosarcoma and correlated with their proliferative activities. METHODS: Immunohistochemical assays for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) were used in a series of eight dedifferentiated chondrosarcomas of bone. The cartilaginous component was low grade (Grade I-II) in five cases. It was predominantly low grade with foci of a high grade (Grade III) chondrosarcoma in the remaining three cases. The noncartilaginous (dedifferentiated) high grade component consisted of malignant fibrous histiocytoma in five cases and osteosarcoma in three. RESULTS: Regardless of the histological type, diffuse strong nuclear staining for p53 occurred in the high grade noncartilaginous component of all eight of the tumors. The low grade cartilaginous component of six cases was negative for p53, with focal weak staining in the two remaining cases. The high grade cartilaginous component showed strong positive staining for this protein in all three cases. Ki-67 and PCNA expression were similar to that of p53. CONCLUSIONS: The percentage of p53 positive staining roughly was parallel to the proliferating fraction of cells in various components of dedifferentiated chondrosarcoma. Moreover, p53 overexpression was consistently present in the high grade noncartilaginous (dedifferentiated) component of the tumor and was accompanied by increased proliferative activity.

Cell Differentiation↗
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↗