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H Moch

Publications and source records attributed to H Moch.

At least 109 records · Page 6Linked to original sources
PubMed1995

Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and metastatic bladder cancer.

To study the relationship of tumor genomic heterogeneity with bladder cancer phenotype and p53 gene alterations, 138 primary bladder tumors were examined by dual labeling fluorescence in situ hybridization (FISH) using probes for chromosome 17 centromere (p17H8) and p53 (17p13.1). The number of different aneusomic populations > 5% (and monosomic populations > 20%) of cells served as a marker for heterogeneity. Nuclear p53 overexpression and Ki67 labeling index (Ki67 LI) were determined by immunohistochemistry. The number of aneusomic populations was 0 in 53 tumors, 1 in 18, 2 in 47, 3 in 9, and > 3 in 11 tumors. Presence of aneusomy was associated with tumor grade and stage (P < 0.0001 each). Ki67 LI was low in disomic tumors (11.0 +/- 7.7), higher in tumors with 1-3 aneusomic populations (17.4 +/- 11.3), and highest in tumors with > 3 aneusomic populations (25.8 +/- 10.9; P = 0.02 for > 3 vs. 1-3 populations). Aneusomy and heterogeneity were associated with p53 alterations. Aneusomy was seen in 35% of tumors with neither p53 expression nor p53 deletion but in 97% of tumors with both p53 deletion and expression. Nine of 11 tumors with > 3 aneusomic populations exhibited both p53 deletion and overexpression. To study genomic heterogeneity in tumor progression, two recurrences and three metastases of a tumor with known erbB-2 amplification were examined for centromere 17 and erbB-2 copy number. A considerable heterogeneity in centromere 17 and erbB-2 gene copy number was found in both recurrences and metastases, indicating a marked genomic instability in these metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell↗
PubMed1995

Y chromosome loss detected by FISH in bladder cancer.

To examine the significance of Y chromosome losses in bladder cancer, fluorescence in situ hybridization (FISH) was used to determine its prevalence and associations with known parameters of malignancy. Cells were dissociated from formalin-fixed paraffin-embedded bladder tumors from 68 male patients and from 11 post-mortem bladder washes of male patients with a negative bladder cancer history, and were examined by FISH using centromeric probes for chromosomes X, Y, 7, 9, and 17. Nullisomy for chromosome Y was seen in 23 of 68 tumors (34%), monosomy in 28 of 68 tumors (41%), and polysomy in 17 of 68 tumors (25%). There was no association between chromosome Y loss and tumor grade, stage, tumor growth fraction (Ki67 LI), p53 immunostaining, and presence of p53 deletions. Patient age was higher for tumors with a Y loss (73.5 +/- 12.0 years) than for tumors without Y loss (66.6 +/- 10.8 years; p = 0.0207). In one normal bladder wash, a distinct subpopulation (38% of cells) with Y nullisomy was seen. These data suggest that Y loss is a frequent event that can occur early in bladder cancer, although there is no evidence for a role of Y loss in tumor progression.

Age Factors↗
PubMed1995

Chromosome-9 loss detected by fluorescence in situ hybridization in bladder cancer.

A loss of chromosome-9 material is one of the most frequent genomic aberrations known in bladder cancer. In order to better understand the role of chromosome-9 losses in bladder cancer, 125 formalin-fixed and 37 unfixed bladder tumors were examined using fluorescence in situ hybridization (FISH). A repetitive probe for a pericentromeric region on 9q12 (pHUR98) was applied for chromosome-9 copy-number enumeration. Under-representation of chromosome 9 was found in 74 of 162 cases. There was no association between loss of chromosome 9 and increased grade or stage, papillary growth pattern, p53 protein expression, or tumor-cell proliferation (Ki-67). These data show that chromosome-9 loss is an early event in bladder-cancer development, occurring independently of p53 alterations. In order to determine the prevalence of large sub-regional chromosome-9 deletions, dual hybridizations with pHUR98 and cosmid probes for 9q34, 9q22, and 9p21 were performed. Partial deletion was detected in only 1 of 36 cases for 9q34 and in 1 of 24 cases for 9p21. Surprisingly, amplification of the interferon alpha locus on 9p21 was seen in 1 of 24 tumors. The finding of 9p amplification may indicate the site of an oncogene relevant for bladder cancer.

Chromosome Deletion↗
PubMed1995

Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder.

Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.

Adolescent↗
PubMed1995

Karyomegalic interstitial nephritis: further support for a distinct entity and evidence for a genetic defect.

Karyomegalic interstitial nephritis was first described in 1979 by Mihatsch, who was reporting three such cases. We report here four additional cases as well as two family investigations. Our findings support the association of karyomegaly and interstitial nephritis as a distinct entity. Typical clinical features are asymptomatic progressive renal failure in the third decade of life and recurrent infections, mostly of the upper respiratory tract. Histologic alterations consist of markedly enlarged and hyperchromic nuclei in many tubular epithelial cells throughout the nephron accompanied by interstitial fibrosis in the surrounding atrophic tubules. Karyomegaly is not limited to the kidneys. In one case, autopsy revealed karyomegaly in epithelial and mesenchymal cells of many other organs. However, no association of karyomegaly with further histologic damage is evident except in the kidneys. Because of the familial clustering, karyomegalic interstitial nephritis seems to be an inherited disease. Examination of the nuclear proliferation-associated structures proliferating cell nuclear antigen/cyclin, Ki 67, and p53 suggests an inhibition of mitosis in karyomegalic cells. The finding of the same HLA haplotype, A9/B35, in four of six HLA-typed cases suggests the possibility of a genetic defect on chromosome 6, which is inherited and linked to the HLA locus.

Adult↗
PubMed1995

Ureteral amyloid deposits of beta 2-microglobulin origin in both kidney recipients of 1 donor.

We report on 2 renal transplant recipients with ureteral amyloid deposits, each of whom received 1 kidney from the same donor. Ureteral stenosis developed in both cases. Immunohistochemistry revealed beta 2-microglobulin derived AB amyloid within the stenotic parts of the ureters, which to our knowledge has not been described previously at that site. Usually AB amyloid is found in patients on long-term hemodialysis. Amyloid transfer by transplantation as a possible cause for ureteral stenosis was excluded because the donor had had normal renal function and autopsy showed no evidence of amyloidosis. It is more likely that the secondary deposit of AB amyloid in the transplanted ureters was facilitated by preexisting ischemic ureteral damage.

Amyloidosis↗
PubMed1995

c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization.

Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.

Chromosomes, Human, Pair 8↗
PubMed1994

Epidermal-growth-factor-receptor expression is associated with rapid tumor proliferation in bladder cancer.

Epidermal-growth-factor-receptor (EGF-r) expression has been proposed as a prognostic marker in bladder cancer and is associated with rapid proliferation in cell lines. Ninety-three fresh and 74 formalin-fixed bladder tumors were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry to assess the relationship between EGF-r expression and proliferation as well as the prevalence of epidermal-growth-factor-receptor (EGF-r) gene amplification. EGF-r expression was strongly associated with BUdr labeling index, grade and stage. EGF-r expression emerged as a stronger predictor of tumor proliferation than grade or stage in analysis of variance. Rapid tumor proliferation might be responsible for bad prognosis reported in EGF-r positive bladder tumors. Also chromosome 7 copy number was associated with grade and stage. EGF-r gene amplification was uncommon (5 of 107 tumors). However, FISH analysis allowed characterization of the pattern of amplification, with clustering of signals suggestive of intrachromosomal amplification more common than diffuse distribution consistent with extrachromosomal amplification.

Bromodeoxyuridine↗
PubMed1994

[Systemic karyomegaly with chronic interstitial nephritis. Discussion of the disease picture based on an autopsy case].

Systemic karyomegaly associated with interstitial nephritis was first described in 1978 by Mihatsch. Seven cases have been reported to date. We give an account of an autopsy case of systemic karyomegaly in a 30-year-old Italian man. Bizarre enlargement of nuclei was found in renal tubular epithelial cells, Schwann cells and in smooth muscle cells of vessels and bowel and, less obviously, in endothelial and adventitial cells of vessels, in alveolar epithelial cells and in astrocytes of the brain. These findings were associated with chronic interstitial nephritis, nonspecific hepatopathy, adenocarcinoma of the rectum and multiple sclerosis. The clinical course was marked by chronic renal failure, chronic haemodialysis and renal transplantation. The patient died 8 years after diagnosis in septic-toxic shock. The aetiology and pathogenesis of the disease are discussed.

Adenocarcinoma↗
PubMed1994

p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer.

Tumor proliferation in bladder cancer is associated with tumor behavior. To assess the association between Ki-67 labeling index (LI), p53, and c-erbB-2 overexpression, formalin-fixed tissue samples of 160 patients with transitional cell carcinoma (TCC) of the urinary bladder were studied by immunohistochemistry. Ki-67 LI was strongly associated with tumor stage (P < .0001), tumor grade (P < .0001), and p53 status (P = .0014) but not with erbB-2 overexpression (P > .2). Ki-67 LI was higher in p53-positive tumors (19%) than in p53-negative tumors (14%) when all stages were compared. Ki-67 LI was independent of p53 expression in pTa tumors (p53-positive, 9%; p53-negative, 11%), showing that p53 overexpression alone is not sufficient to induce rapid tumor cell proliferation in pTa tumors. Ki-67 LI also was independent of p53 expression in pT2 to pT4 tumors (p53-positive, 20%; p53-negative, 23%), indicating that p53 expression is not necessary for rapid tumor cell proliferation in advanced stages. However, there was a striking difference in Ki-67 LI between p53-positive pT1 tumors (22.0% +/- 8.8 standard deviation [SD]; n = 20) and p53-negative pT1 tumors (9.7 +/- 8.3 SD; n = 22; P = .0001). These results suggest that increased proliferation in p53-positive pT1 tumors is caused by additional alterations that occur during tumor progression.

Carcinoma, Transitional Cell↗
PubMed1994

A new case of malignant mesothelioma of the tunica vaginalis testis. Immunohistochemistry in comparison with an adenomatoid tumor of the testis.

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor with 41 previously reported cases. The histological and immunohistological features of a new case in an 80-year-old patient are described and compared with an adenomatoid tumor of the tunica vaginalis testis, which is considered to be the benign variant of malignant mesothelioma. Both tumors revealed strong cytoplasmic staining for a panepithelial antibody (Lu-5) and membranous staining for BMA-120 (a mesothelial/endothelial cell marker) but yielded negative staining results with the endothelial cell markers QBend-10 (CD 34), Factor VIII-related antigen (vWF) and UEA-1. There was also negative staining for CEA, Ber-EP4, HEA-125 and Blood group related antigens A, B, H. An identical staining pattern was evident in normal and reactive mesothelial cells. Our data support a mesothelial rather than an endothelial derivation of the adenomatoid tumor studied.

Aged↗
PubMed1994

Primary non-Hodgkin's lymphoma of the lung. Will videothoracoscopic biopsy change decision-making with regard to resection of this disease?

We report on a 57-year-old male presenting with cough and chest pain as well as a chronic infiltrate in the right posterior basel segment. Antibiotic treatment had been unsuccessful, CT-guided needle-biopsy and bronchoscopy had failed to forward reliable results. Thus, videothoracoscopic biopsy was performed and histologic diagnosis of a low-grade non-Hodgkin's lymphoma was obtained. The tumor was left in situ and single-agent chemotherapy was initiated for reasons which are discussed. Up to now localized pulmonary lymphomas were mainly resected in the course of an exploratory thoracotomy because the disease often could not be diagnosed with certainty previously. It is discussed whether surgical resection is still the best choice or other treatment modalities should be preferred.

Biopsy↗
PubMed1994

Late urinary bladder metastases after radical resection of prostatic carcinoma.

The case of a 69-year-old man who underwent radical prostatectomy because of carcinoma of the prostate is reported. A preoperative cystoscopy was normal. The histological evaluation of the radical prostatectomy showed an infiltration of the urethral margin. 14 months later, cystoscopy showed papillary metastases of the prostatic carcinoma in the bladder. Immunohistochemistry and flow cytometry for various prognostic factors showed a high malignant potential of this tumor. Preoperative transurethral instrumentation for the treatment of urethral strictures may be responsible for the dissemination of tumor cells into the bladder.

Adenocarcinoma↗
PubMed1994

Clinical and pathological features of highly malignant prostatic carcinomas with metastases to the penis.

Since 1885, 73 penile metastases of a primary carcinoma of the prostate have been reported. There is no standardized therapy as various therapeutic methods have produced variable results. The authors present their experiences with 2 recent cases. In some cases, total penectomy can relieve untolerable pain. Immunohistochemistry and flow cytometry for various prognostic factors showed a high malignant potential of carcinomas of the prostate metastasizing to the penis. Screening for various prognostic factors could favor an initial, more radical surgical approach in some cases, thus avoiding later tumor progression.

Adenocarcinoma↗
PubMed1994

[Primary detection of malignant mesothelioma of the tunica vaginalis testis using the BMA-120 monoclonal antibody].

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor, with only 40 cases previously described in the literature. Treatment consists of inguinal orchiectomy with close-follow up [1]. Asbestose exposure, trauma and hydrocele have been implicated as risk factors. We describe a histopathological examination with the BMA antibody (Behring, Marburg, Germany) and the Lu-5 antibody (Hoffmann-La Roche, Basel, Switzerland). Furthermore, we describe the patient's history and the management according to preceding reports in the literature.

Aged↗
PubMed1994

Physical deletion of the p53 gene in bladder cancer. Detection by fluorescence in situ hybridization.

To understand better the role of physical p53 deletion in bladder cancer, 106 formalin-fixed and 45 unfixed bladder tumors were examined using fluorescence in situ hybridization. Probes for centromere 17 and the p53 locus were hybridized simultaneously to interphase tumor cells to analyze p53 and chromosome 17 copy number on a cell by cell basis. 17p deletion was found in four of 43 pTa tumors, 18 of 43 pT1 tumors and 29 of 58 pT2-4 tumors (P = 0.0001). 17p deletion was also highly correlated with grade (P = 0.0001) and with p53 immunostaining (P = 0.0005). Chromosome 17 polysomy was associated with stage, grade, 17p deletions, and p53 immunostaining (P = 0.0001). The strong difference in centromere 17 copy number and 17p deletions between pTa and pT1 tumors supports a relevant biological distinction between pTa and pT1 tumors.

Alleles↗
PubMed1993

Heterogeneity of erbB-2 gene amplification in bladder cancer.

erbB-2 amplification and overexpression have been suggested as potentially useful prognostic markers in bladder cancer. We examined 141 bladder tumor specimens (45 fresh tissue samples and 96 formalin fixed tissue blocks) for erbB-2 amplification using fluorescence in situ hybridization. A dual labeling hybridization using a repetitive pericentromeric probe specific for chromosome 17 and a cosmid probe for the erbB-2 locus was performed to analyze the erbB-2 copy number in relation to chromosome 17 copy number on a cell by cell basis. Amplification (more than twice as many erbB-2 signals as centromere 17 signals per tumor) was found in 10 of 141 tumors. There was considerable heterogeneity in erbB-2 amplification. In a given tumor there was a wide range of erbB-2 copy number in amplified cells. The arrangement of erbB-2 signals in clusters in all amplified cases suggests that erbB-2 amplification occurs intrachromosomally in bladder cancer. Amplification was found only in tumors with aneusomy of chromosome 17 and was more frequent in pT2-T4 tumors than in pTa/T1 tumors. Overexpression was present without amplification in 51 tumors. All tumors with erbB-2 amplification showed erbB-2 overexpression. However, in 5 samples the proportion of cells with amplification was significantly lower than the fraction of cells with overexpression, indicating coexistence of two different mechanisms leading to overexpression in these tumors.

Bromodeoxyuridine↗