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Bogdan Czerniak

Publications and source records attributed to Bogdan Czerniak.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of outcome in patients undergoing postchemotherapy retroperitoneal lymph node dissection for testicular cancer.

BACKGROUND: The management of metastatic nonseminomatous germ cell tumors (NSGCT) frequently consists of systemic chemotherapy followed by retroperitoneal lymph node dissection (PC-RPLND). The aim of the present study was to evaluate the authors' PC-RPLND experience and identify predictors of outcome in these patients. METHODS: Between 1980 and 2003, 236 patients with clinical Stage IIA-III NSGCT underwent PC-RPLND. Their medical records were retrospectively reviewed for pertinent clinical and treatment-related outcomes. The 5-year disease-specific and recurrence-free survival was 85% and 75%, respectively, with the median length of follow-up after RPLND 45 months (6-250 months). RESULTS: The median age of patients at diagnosis was 28 years, with all patients receiving systemic chemotherapy (median of 5 cycles) before RPLND. On multivariate analysis, predictors of poorer disease-specific survival (DSS) included systemic symptoms at presentation (P = .05), elevated pre-RPLND serum alpha fetoprotein (AFP, P = .006) and beta-human chorionic gonadotropin (HCG, P = .004), postoperative complications (P = .03), and recurrence (P < .0001). Predictors of poorer recurrence-free survival (RFS) included advanced clinical stage (IIC-III, P = .001) and presence of viable tumor in the RPLND specimen (P = .03). A pre-RPLND serum AFP > 9 ng/mL and HCG > 4.1 mIU/mL were found to predict a worse DSS (P = .03 and .03, respectively). CONCLUSIONS: In patients undergoing PC-RPLND, preoperative tumor markers and the occurrence of postoperative complications or recurrence are predictive of poorer DSS. Advanced clinical stage and viable tumor in the surgical specimen predict worse RFS.

Adolescent↗
PubMed2006

Immediate versus staged urethrectomy in patients at high risk of urethral recurrence: is there a benefit to either approach?

OBJECTIVES: To compare treatment-related outcomes of immediate and staged urethrectomy in patients at high risk of urethral recurrence. METHODS: We retrospectively identified 76 male patients with cystectomy for transitional cell carcinoma of the bladder who had undergone urethrectomy in the absence of established urethral recurrence. Concomitant cystoprostatectomy and urethrectomy was performed in 57 patients and staged urethrectomy in 19 patients. The criteria for staged urethrectomy were the presence of a positive urethral margin or established transitional cell carcinoma of the urethra in the cystectomy specimen. The mean interval from cystectomy to staged urethrectomy was 4.7 months (range 1.4 to 14). RESULTS: The most common pathologic finding of the urethrectomy specimens was prostatic duct involvement (31.6%) in the immediate urethrectomy group and Stage pT0 in the delayed urethrectomy group (73.7%). No statistically significant difference in disease-specific survival was noted between the immediate and staged groups (P = 0.14). Similarly, no difference was noted in postoperative complication rates or total operative blood loss (P = 0.77 and P = 0.64, respectively). However, a slight benefit for immediate urethrectomy was noted in the total duration of hospitalization (P = 0.01). The presence of local or distant recurrence was a predictor of disease-specific survival (P = 0.02 and P = 0.02, respectively). CONCLUSIONS: Immediate and staged urethrectomy appear to be similar in surgical morbidity and disease-specific survival. A benefit was noted for the immediate group in the total duration of hospitalization. The development of local or distant recurrence was a predictor of poor survival.

Adult↗
PubMed2006

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia.

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.

Aged↗
PubMed2006

Molecular diagnosis of sarcomas: chromosomal translocations in sarcomas.

CONTEXT: Sarcomas are rare, numerous in type, and often difficult to definitively classify. Work in the last 2 decades has revealed that a significant subset of sarcomas are associated with specific chromosomal translocations producing chimeric (fusion) genes that play a role in the sarcomas' biology and are helpful in their differential diagnosis. OBJECTIVE: To briefly review the sarcomas associated with specific translocations presenting Ewing sarcoma and synovial sarcoma as archetypes and to further explain how cytogenetic and molecular biologic approaches are being used in the diagnosis of sarcomas. DATA SOURCES: This work is based on a selected review of the relevant medical and scientific literature and our extensive experience with molecular testing in sarcomas. CONCLUSIONS: In addition to, and complementing, the traditional diagnostic methods of examination of hematoxylin-eosin stained slides, immunohistochemistry, and sound clinical-pathologic correlation, additional cytogenetic and molecular biologic methods are being increasingly utilized and relied on in sarcoma pathology. These methods include chromosomal karyotyping, fluorescence in-situ hybridization, spectral karyotyping, and polymerase chain reaction- based methods for demonstrating specific chromosomal translocations and fusion genes. Understanding the basis of these methods and their application is critical to better provide accurate and validated specific diagnoses of sarcomas.

Bone Neoplasms↗
PubMed2006

Dual-track pathway of bladder carcinogenesis: practical implications.

CONTEXT: The concept of a dual-track pathway in bladder carcinogenesis postulates that bladder cancer develops via 2 distinct but somewhat overlapping pathways, termed the papillary and nonpapillary. Approximately 80% of bladder carcinomas consist of superficial exophytic papillary lesions that originate from urothelial hyperplasia. These typically low-grade papillary tumors may recur, but they rarely invade the bladder wall or metastasize. The remaining 15% to 20% of tumors represent high-grade solid nonpapillary bladder carcinoma, which arise from high-grade intraurothelial neoplasia. These tumors aggressively invade the bladder wall and have a high propensity for distant metastasis. OBJECTIVE: To summarize the scientific literature and provide a clinicopathologic review of the dual-track concept of bladder carcinogenesis with its important implications. DATA SOURCES: Relevant articles indexed in PubMed (National Library of Medicine) between 1974 and 2005. CONCLUSIONS: Although the characteristics of papillary and nonpapillary tumors are quite dissimilar, current evidence implies that both forms of bladder cancer start as a clinically occult clonal expansion of preneoplastic lesions that occupy large areas of the bladder mucosa.

Carcinoma, Squamous Cell↗
PubMed2005

Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies.

HIN-1 (high in normal-1) is a putative cytokine with growth inhibitory activities and is downregulated by aberrant methylation in breast cancers. We studied HIN-1 methylation status in many types of adult and pediatric malignancies and cell lines. We examined the expression of HIN-1 mRNA in 52 cell lines and the promoter methylation status in the cell lines and in over 800 primary tumors representing 17 tumor types using methylation specific PCR. Promoter methylation was observed in 73% of breast cancer, 67% of nonsmall cell lung cancer (NSCLC), 30% of small cell lung cancer (SCLC) and 57% of malignant mesothelioma (MM) cell lines, and methylation was completely correlated with loss of expression. Expression negative cell lines restored HIN-1 expression after treatment with 5-aza-2'-deoxycytidine. Promoter methylation of HIN-1 was found in 90% of retinoblastomas, 73% of Wilms' tumors, 61% of rhabdomyosarcomas, 57% of breast cancers, 52% of prostate cancers, 40% of MMs, 28% of NSCLCs and 27% of lymphomas. Methylation frequencies in colorectal cancers, cervical cancers, bronchial carcinoids, SCLCs, neuroblastomas, osteosarcomas, leukemia, medulloblastomas and bladder cancers were lower (4-21%), while hepatoblastomas lacked methylation. HIN-1 methylation was rarely detected in nonmalignant tissues (8 of 165, 5%). Aberrant methylation of HIN-1 with loss of expression is a common event and may contribute to the pathogenesis of many types of human malignancies.

Adult↗
PubMed2005

Malignant mesothelioma of the tunica vaginalis.

OBJECTIVES: To review our experience with the management of malignant mesothelioma of the tunica vaginalis with emphasis on disease-related outcomes. METHODS: A retrospective chart review of patients seen during the past 25 years at our cancer center identified 5 cases of malignant mesothelioma of the tunica vaginalis. RESULTS: The mean age of patients at presentation was 61.2 years (range 57 to 83). Asbestos exposure was identified in 4 patients. Three patients presented with clinical symptoms suggestive of a hydrocele and two presented with clinical signs of an inguinal hernia. The final diagnosis was established intraoperatively in 1 patient and postoperatively in the remaining 4. Radical orchiectomy or hernia sac with spermatic cord excision was the primary treatment modality. Although radical surgical treatment achieved negative resection margins in 4 cases, 4 of 5 patients died of the disease, with a mean disease-specific survival of only 29 months (range 5 to 68). Regional inguinal lymph node metastasis developed in 3 of 5 patients. Salvage therapy did not prove curative in the 2 patients who received it. CONCLUSIONS: Malignant mesothelioma of the tunica vaginalis constitutes a rare but often fatal malignancy of the male genitalia. This diagnosis should be suspected in patients exposed to asbestos and presenting with clinical symptoms of either hydrocele or inguinal hernia. Frequent inguinal lymph node involvement indicates a potential role of inguinal lymphadenectomy in the primary treatment.

Aged↗
PubMed2005

Alterations in transcription clusters underlie development of bladder cancer along papillary and nonpapillary pathways.

Bladder cancer develops in the urothelial lining from intraurothelial preneoplasia via two pathways, papillary and nonpapillary, which correspond to nonaggressive and aggressive forms of the disease. Because these two forms of cancer may develop via distinct molecular events, we examined the gene expression patterns in the development of bladder cancer from preneoplasia along papillary and nonpapillary pathways. The expression profiles of 19 pairs of RNA samples from adjacent urothelium and tumors were analyzed using cDNA microarrays. For selected genes their expressions were verified on a cohort of 251 bladder cancer patients using tissue microarray and immunohistochemistry and were related to clinicopathological parameters including follow-up data. We identified alterations in seven gene clusters controlling proliferation, differentiation, and programmed cell death that were common for papillary and nonpapillary cancer. In contrast, genes controlling cellular and stromal interactions were altered in the nonpapillary cancer. The expression levels of only two genes from this group could be used to define an aggressive form of the disease. Tumors characterized by the low expression of e-cadherin and the high expression of DNA alpha-topoisomerase II had a high propensity for distant metastasis and were associated with poor survival.

DNA, Complementary↗
PubMed2005

High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis.

We attempted to identify deleted segments in two model tumor suppressor gene loci on chromosomes 13q14 and 17p13 that were associated with clonal expansion of in situ bladder preneoplasia using single nucleotide polymorphisms (SNPs)-based whole-organ histologic and genetic mapping. For mapping with SNPs, the sequence-based maps spanning approximately 27 and 5 Mb centered around RB1 and p53, respectively, were assembled. The integrated gene and SNP maps of the regions were used to select 661 and 960 SNPs, which were genotyped by pyrosequencing. Genotyping of SNPs was performed on DNA samples corresponding to histologic maps of the entire bladder mucosa in human cystectomy specimens with invasive urothelial carcinoma. By using this approach, we have identified deleted regions associated with clonal expansion of intraurothelial neoplasia; which ranged from 0.001 to 4.3 Mb (average 0.67 Mb) and formed clusters of discontinuous deleted segments. The high resolution of such maps is a prerequisite for future positional targeting of genes involved in early phases of bladder neoplasia. This approach also permits analysis of the overall genomic landscape of the involved region and discloses that a unique composition of noncoding DNA characterized by a high concentration of repetitive sequences may predispose to deletions.

Carcinoma in Situ↗
PubMed2004

Molecular detection of noninvasive and invasive bladder tumor tissues and exfoliated cells by aberrant promoter methylation of laminin-5 encoding genes.

Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize and grow, cancer cells must invade and destroy the basement membrane. Our previous work has shown that epigenetic inactivation is a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies to resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and voided urine; n = 71) and correlated the data with clinicopathologic findings. Nonmalignant urothelium had uniform expression of LN5 genes and lacked methylation. The methylation frequencies for LN5 genes in tumors were 21-45%, and there was excellent concordance between methylation in tumors and corresponding exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival. Of particular interest, methylation frequencies of LAMA3 helped to distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest that methylation of LN5 genes has potential clinical applications in bladder cancers.

Cell Line, Tumor↗
PubMed2004

Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy.

PURPOSE: Patients with locally advanced (ie clinically extravesical) transitional cell carcinoma are at high risk for recurrence after cystectomy. Although randomized trials have established an incremental benefit from the addition of chemotherapy in this setting, many patients still have disease relapse, and therefore it is necessary to determine patient and tumor characteristics that correlate with outcome in this setting. We investigated the tumor expression of several metastasis related genes and the association of gene expression with disease specific survival of patients with locally advanced transitional cell carcinoma treated randomized to either neoadjuvant or adjuvant chemotherapy and radical cystectomy. MATERIALS AND METHODS: Archival paraffin embedded specimens were available for 64 patients enrolled in a clinical trial of the methotrexate, vinblastine, doxorubicin and cisplatin regimen and cystectomy. Only samples obtained before exposure to chemotherapy were studied. The expression of several metastasis related genes, including basic fibroblast growth factor, vascular endothelial growth factor (VEGF), interleukin-8, matrix metalloproteinase (MMP)-9, and E-cadherin were assayed on paraffin sections using a colorimetric in situ hybridization assay. RESULTS: Expression of basic fibroblast growth factor, interleukin-8 and MMP-9 did not correlate with outcome. Expression of VEGF and E-cadherin were strongly related to disease specific survival. In addition, the ratio of MMP-9-to-E-cadherin was strongly prognostic for disease specific survival. CONCLUSIONS: These data advance the hypotheses that VEGF expression and an "invasive phenotype" characterized by the ratio of MMP-9-to-E-cadherin expression are mechanistically relevant to clinically aggressive locally advanced bladder cancers that are not cured by currently available combined modality treatment. Thus, in our view there is a compelling rationale to target these aspects of the malignant phenotype in this patient population.

Adult↗
PubMed2003

Pathologic and molecular aspects of soft tissue sarcomas.

This article retains the conventional approach to the classification of soft tissue sarcomas, dividing them into several major histogenetic categories based on their overall microscopic appearance, tissue differentiation pattern, and biologic potential. The author advocates a multimodal approach, in which four distinctive data sets--clinical, radiographic, microscopic, and, in some cases, molecular--are considered to establish the diagnosis and treatment plan. Such step-wise analysis is more likely to lead to consistency and accuracy as compared with an intuitive approach based on fragmentary data. The author describes individual lesions of soft tissue as clinicopathologic entities and believes that they can be more accurately diagnosed and appropriately treated with the help of data generated by a multidisciplinary team. In addition, this article emphasizes the need to use emerging molecular techniques that can provide important clues for both diagnosis and prognosis.

Clinical Trials as Topic↗
PubMed2003

Chromophobe renal cell carcinoma with sarcomatoid transformation.

We present a rare case of a chromophobe renal cell carcinoma that progressed to a high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had presented with right upper quadrant discomfort and hematuria and subsequently underwent a right radical nephrectomy. Microscopically, the tumor was composed of two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid component. The sarcomatoid component had exhibited aggressive behavior by spreading to a regional lymph node. This case report shows that chromophobe carcinoma can develop a sarcomatoid transformation with a high propensity for invasive growth and metastasis.

Carcinoma, Renal Cell↗
PubMed2003

Sox9, a master regulator of chondrogenesis, distinguishes mesenchymal chondrosarcoma from other small blue round cell tumors.

Over the last decade, a number of "master regulator" genes that control distinct pathways of mesenchymal differentiation have been discovered. These genes are expressed early during embryogenesis and initiate a cascade of gene expression responsible for specific cell lineage commitment. Thus, identification of their products may allow the classification of seemingly primitive, morphologically uncommitted tumors such as small blue round cell tumors. The transcription factor Sox9 has been demonstrated to be a master regulator of the differentiation of mesenchymal cells into chondrocytes. For this reason, we examined the utility of Sox9 in distinguishing mesenchymal chondrosarcoma (a small cell malignancy thought to be derived from primitive chondroprogenitor cells) from other primitive small cell malignancies. Representative sections from 90 cases of small blue round cell tumors (22 mesenchymal chodrosarcoma, 10 neuroblastomas, 11 rhabdomyosarcomas, 9 Ewing's sarcomas/primitive neuroectodermal tumors, 5 desmoplastic small round cell tumors, 7 small cell carcinomas, 6 Merkel cell carcinomas, 6 small cell osteosarcomas, 7 diffuse large B-cell lymphomas, 7 lymphoblastic leukemias/lymphomas, and 5 extraskeletal myxoid chondrosarcomas) were immunohistochemically stained with antibodies to Sox9 protein. All but 1 mesenchymal chondrosarcoma showed positive nuclear staining in both primitive mesenchymal and cartilaginous components of the tumor. All other types of small blue round cell tumors, as well as the lymphomas and leukemias, were negative for Sox9 protein. These findings confirm that mesenchymal chondrosarcoma has phenotypic features corresponding to the early condensational phase of cartilaginous differentiation. More important, Sox9 may serve as a useful tool in the differentiation of small cell malignancies.

Adolescent↗
PubMed2002

Amplification/overexpression of a mitotic kinase gene in human bladder cancer.

BACKGROUND: The mitotic kinase-encoding gene STK15/BTAK/ AuroraA is associated with aneuploidy and transformation when overexpressed in mammalian cells. STK15 overexpression activates an unknown oncogenic pathway that involves centrosome amplification and results in missegregation of chromosomes. Because clinical prognosis and tumor aneuploidy are tightly linked in human bladder cancer, we examined whether increased STK15 copy number and protein levels are linked to aneuploidy in bladder cancers. METHODS: STK15 protein was visualized by immunohistochemistry in 205 formalin-fixed, paraffin-embedded human bladder tumors. STK15 gene copy number was evaluated in 61 tumors by Southern blot hybridization and in 21 of these 61 tumors by fluorescence in situ hybridization (FISH). Copy numbers of chromosomes 3, 17, 20, and 21 were evaluated by FISH with chromosome-specific probes. STK15 expression levels were related to histologic grade, stage, and DNA ploidy of the tumors and to the patients' follow-up data. The chi-square test for association was used to analyze the relationship between STK15 expression and pathologic features. All statistical tests were two-sided. RESULTS: Tumors with low levels of STK15 amplification (3-4 copies) showed minimal deviation in their chromosome copy number and diploid or near-diploid total nuclear DNA content. Tumors with higher levels of STK15 amplification (>4 copies) had a major increase of chromosome copy number and of their total nuclear DNA content, i.e., exhibited pronounced aneuploidy. Elevated expression of STK15 was strongly associated with parameters of clinical aggressiveness including high histologic grade (P<.001), invasion (P<.001), increased rate of metastasis (P<.001), and decreased metastasis-free (P<.001) and overall (P<.001) survival of patients with bladder cancer. CONCLUSION: STK15 gene amplification and associated increased expression of the mitotic kinase it encodes are associated with aneuploidy and aggressive clinical behavior in human bladder cancer.

Adult↗
PubMed2002

Dedifferentiated chondrosarcoma with a noncartilaginous component mimicking a conventional giant cell tumor of bone.

We report a case of dedifferentiated chondrosarcoma in which the dedifferentiated component of the tumor shows a close histologic resemblance to a conventional giant cell tumor of bone. The tumor affected a 30-year-old woman with a long history of left shoulder discomfort and limitation of motion. Radiographic studies revealed a biphasic destructive lesion in the left proximal humerus composed of high-signal lobulated component on T2-weighted magnetic resonance image accompanied by a low signal intensity component exhibiting destructive growth with extension into soft tissue. Microscopically, two different areas consisting of the chondroid tissue and nonchondroid giant cell-rich lesion resembling conventional giant cell tumor of bone were found. Considering that the prognosis and survival associated with these two entities are very different, it is important to be aware of this variant of dedifferentiated chondrosarcoma to avoid the misdiagnosis of conventional giant cell tumor of bone.

Adult↗
PubMed2000

Epithelial Phenotype in Ewing's Sarcoma/Primitive Neuroectodermal Tumor.

Neural differentiation is an integral component of Ewing's sarcoma/primitive neuroectodermal tumor (PNET), which exhibits a continuous spectrum from minimal to prominent neural phenotype. Differentiation of Ewing's sarcomas/PNETs along other lineages or the expression of an epithelial phenotype is less common and-if present-may cause diagnostic difficulties. In this study we evaluated the frequency of epithelial differentiation in formalin-fixed and paraffin-embedded tissues of 33 (22 primary and 11 metastatic) Ewing's sarcomas/PNETs by using an immunohistochemical assay with several antikeratin antibodies. Focal positivity for low- or high-molecular-weight keratins was documented in 18% of the cases, and diffuse coexpression of low- and high-molecular-weight keratins was observed in two cases. Expression of the MIC-2 gene product was documented in 94% of the tumors. The primitive neural phenotype as revealed by expression of either neuron-specific enolase or synaptophysin was observed in 30% of the cases, but coexpression of both neural markers was present in only 15% of the tumors. This study documents that, in addition to primitive neural differentiation, Ewing's sarcomas/PNETs frequently exhibit focal positivity for keratins, with rare strong diffuse coexpression of both low- and high-molecular-weight keratins. The findings indicate that the expression of an epithelial phenotype, at least in a focal fashion, is a relatively frequent finding in otherwise typical Ewing's sarcomas/PNETs. Int J Surg Pathol 8(1):59-65, 2000

Journal Article↗