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Wolfram Müller

Publications and source records attributed to Wolfram Müller.

13 recordsLinked to original sources
PubMed2006

Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased risk of multiple primary tumours. Colorectal cancer in HNPCC is characterised by poor tumour differentiation, an expanding growth pattern, and a pronounced lymphocytic reaction with tumour-infiltrating lymphocytes. AIMS AND METHODS: The mutation spectrum in HNPCC is diverse and in order to clarify whether the HNPCC tumour phenotype is influenced by the underlying genetic alteration, 29 colorectal cancers and 12 adenomas from 24 individuals in two HNPCC families were morphologically and immunohistochemically characterised. RESULTS: The tumour morphology as well as the immunohistochemical expression of beta-catenin varied extensively within the families as well as between synchronous/metachronous colorectal cancers from the same individual. Poor tumour differentiation, an expanding growth pattern, and tumour-infiltrating lymphocytes occurred at higher frequencies in proximal tumours, whereas distal colorectal cancers often lacked distinct HNPCC-associated morphological features. CONCLUSIONS: The clinical, morphological and immunohistochemical variability observed within these families indicates that other mechanisms than the underlying germline mutation influence the HNPCC phenotype. Since morphological features linked to HNPCC are less frequent in distal cancers, it may be particularly relevant to obtain family history and age of onset in these tumours in order to identify individuals with HNPCC.

Adenoma↗
PubMed2006

Gene expression in acute Stanford type A dissection: a comparative microarray study.

BACKGROUND: We compared gene expression profiles in acutely dissected aorta with those in normal control aorta. MATERIALS AND METHODS: Ascending aorta specimen from patients with an acute Stanford A-dissection were taken during surgery and compared with those from normal ascending aorta from multiorgan donors using the BD Atlas Human1.2 Array I, BD Atlas Human Cardiovascular Array and the Affymetrix HG-U133A GeneChip. For analysis only genes with strong signals of more than 70 percent of the mean signal of all spots on the array were accepted as being expressed. Quantitative real-time polymerase chain reaction (RT-PCR) was used to confirm regulation of expression of a subset of 24 genes known to be involved in aortic structure and function. RESULTS: According to our definition expression profiling of aorta tissue specimens revealed an expression of 19.1% to 23.5% of the genes listed on the arrays. Of those 15.7% to 28.9% were differently expressed in dissected and control aorta specimens. Several genes that encode for extracellular matrix components such as collagen IV alpha2 and -alpha5, collagen VI alpha3, collagen XIV alpha1, collagen XVIII alpha1 and elastin were down-regulated in aortic dissection, whereas levels of matrix metalloproteinases-11, -14 and -19 were increased. Some genes coding for cell to cell adhesion, cell to matrix signaling (e.g., polycystin1 and -2), cytoskeleton, as well as several myofibrillar genes (e.g., alpha-actinin, tropomyosin, gelsolin) were found to be down-regulated. Not surprisingly, some genes associated with chronic inflammation such as interleukin -2, -6 and -8, were up-regulated in dissection. CONCLUSION: Our results demonstrate the complexity of the dissecting process on a molecular level. Genes coding for the integrity and strength of the aortic wall were down-regulated whereas components of inflammatory response were up-regulated. Altered patterns of gene expression indicate a pre-existing structural failure, which is probably a consequence of insufficient remodeling of the aortic wall resulting in further aortic dissection.

Journal Article↗
PubMed2004

Expression of the tyrosine kinase c-kit is an independent prognostic factor in patients with small cell lung cancer.

In a retrospective analysis of 203 patients with small cell lung cancer (SCLC), we examined the prognostic value of c-kit expression on survival. Expression of c-kit was examined immunohistochemically in formalin-fixed, paraffin-embedded tissue sections. c-kit was observed in 87.7% of SCLC tumors. Using the Kaplan-Meier model, we found that lack of c-kit expression was associated with significantly shorter survival time compared to the presence of c-kit expression (mean survival 151 +/- 27 vs. 358 +/- 49 days, p = 0.0084). Moreover, the proportion of c-kit(+) cells within the tumor was also related to survival time. Patients with tumors in which >75% of cells stained positive for c-kit had a mean overall survival time of 424 (+/-72) compared to 295 (+/-67) days for patients with 25-75% c-kit(+) tumor cells. Patients with tumors containing <25% c-kit(+) cells had the worst survival, with 164 (+/-24) days (p = 0.0033). Further parameters associated with short survival times were low performance status, elevated levels of lactate dehydrogenase and higher stage according to the TNM classification. Multivariate analysis using the Cox regression model showed that the proportion of c-kit(+) cells within the tumor specimen was one of 3 independent prognostic parameters (p = 0.004) for overall survival next to TNM classification (p = 0.001) and performance status (p < 0.001).

Aged↗
PubMed2003

The inframe MSH2 codon 596 deletion is linked with HNPCC and associated with lack of MSH2 protein in tumours.

Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by germline truncating mutations in DNA mismatch repair (MMR) genes. Whether or not missense or inframe mutations are disease-associated has become a practical clinical problem, because predictive genetic testing is employed to select high-risk persons for clinical examinations. Clinical examinations may reveal polyps to be removed and prevent cancer. One large kindred applying for health care had a N596del mutation in the MSH2 gene. The aim of this study was to determine whether or not the inframe mutation in this family was associated with disease, and to examine the tumours for presence of the MSH2 protein by immunohistochemistry. We demonstrated that the mutation was linked to disease with lod score 5.7 in the family, and all examined, but one manifest cancer, lacked the MSH2 protein.

Adenosine Triphosphatases↗
PubMed2003

Surgical treatment of renal artery dissection in 25 patients: indications and results.

OBJECTIVE: Results of surgical revascularization in 25 patients with renal artery dissection (RAD) over 14 years, with mean follow-up of 55.3 months (range, 10-111 months), were analyzed. Indications for surgery were renovascular hypertension and preservation or improvement of kidney function. PATIENTS AND METHODS: Two patients (both 20 years of age) underwent emergency surgery after severe trauma; 23 patients (mean age, 41 years) underwent elective surgery in a chronic stage of disease. Preoperative, postoperative, and follow-up examinations included duplex ultrasound scanning, determination of serum creatinine and urea concentrations, and evaluation of blood pressure control. All long-term patients underwent digital subtraction angiography preoperatively and postoperatively. All histologic specimens of resected renal arteries were re-evaluated by two independent pathologists. RESULTS: Histologic re-evaluation confirmed the traumatic origin in 2 patients who underwent emergency surgery and 1 who underwent elective surgery. Renal artery dissection developed spontaneously, with no histologic signs of trauma or fibromuscular dysplasia, in 22 patients. In 17 revascularized kidneys (61%) a kidney infarction had already developed preoperatively, and the kidneys were diminished in size or function. Results of revascularization and improvement of hypertension depended on preoperative extent of renal infarction. Hypertension resolved or improved in 86% of patients without preoperative kidney damage, but in only 38% with preoperatively damaged kidneys. Kidney function was preserved in 23 of 28 revascularized kidneys (82%). During follow-up, late renal artery occlusion developed in 3 kidneys. CONCLUSIONS: Renal artery dissection can be effectively treated with surgical revascularization. Primary nephrectomy should be considered only in patients with a large ischemic kidney infarction, with significant deterioration of kidney function, to effectively cure or improve severe renovascular hypertension.

Adult↗
PubMed2002

Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma.

BACKGROUND: It has been reported that p53 regulates the G2-M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Tissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry. RESULTS: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC. CONCLUSIONS: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC.

Adult↗
PubMed2002

High frequency of microsatellite instability and loss of mismatch-repair protein expression in patients with double primary tumors of the endometrium and colorectum.

BACKGROUND: Patients with the familial syndrome hereditary nonpolyposis colorectal carcinoma (HNPCC) exhibit an increased risk for several tumor types, of which the greatest lifetime risk is for colorectal and endometrial carcinoma. HNPCC is caused by a germline mutation in one of several identified mismatch repair (MMR) genes and typically presents with microsatellite instability (MSI) and frequent loss of MMR protein expression in the tumor tissue. The objective of this study was to estimate the proportion of double primary tumors of the endometrium and colorectum that displays tumor characteristics suggestive of MMR deficiency. METHODS: The authors used the southern Sweden regional population-based Cancer Registry to identify women who developed double primary tumors of the endometrium and colorectum. Of the 256 women who were diagnosed with carcinoma at both of these sites during the period 1958-1998, 39 women had developed their first tumor before age 50 years. The authors successfully retrieved 67 tumors from 36 of these patients and analyzed them for MSI and immunohistochemical expression of the MMR genes, MLH1, MSH2, and MSH6. RESULTS: The MSI status of the 67 tumors was high MSI in 37 tumors, low MSI in 13 tumors, and microsatellite stable (MSS) in 17 tumors. Immunohistochemical loss of MMR protein expression was correlated with MSI status and was demonstrated in 29 high MSI tumors, in 1 low MSI tumor, and in 1 MSS tumor. A concordant loss of the same MMR protein in both tumors was found in 12 of 27 patients. CONCLUSIONS: The authors demonstrated a high frequency of MSI (75%) in tumors from women with endometrial and colorectal carcinoma who had their first tumor diagnosed before age 50 years and observed concordant immunohistochemical loss of MMR protein expression, suggestive of a possible underlying germline mutation, in 12 of 27 patients (44%). They concluded that double primary malignancies of the colorectum and endometrium at a young age should make the clinician suspect HNPCC.

Adult↗
PubMed2002

Refined mapping of allele loss at chromosome 10q23-26 in prostate cancer.

BACKGROUND: Allele loss of at least two segments in 10q, one mapping to the PTEN gene and one more distal were described in prostate cancer, with loss more frequent in advanced prostate cancer. METHODS: A 63 cM region from 10q23 to q26 was studied for allele loss (LOH) in 59 prostate cancer samples using a dense map of microsatellite markers. RESULTS: LOH of at least one marker in 10q was observed in 13/59 tumors. LOH increased with grade and stage. Detailed deletion mapping identified three regions of allele loss. The first region mapped to the site of the PTEN gene, the second is defined by loss of one marker, D10S1692, in one tumor, and the third is defined between markers D10S1757 and D10S587, including DMBT, with a subregion of approximately 1.2 Mb mapping between markers D10S209 and D10S1679, lost in one tumor. CONCLUSIONS: LOH at the PTEN gene is frequent but mutations in the remaining allele were not detected by SSCP-screening. There may be more than two tumor suppressor (TS) genes mapping more distal of PTEN. The site for these putative TS genes can now be mapped with a dense set of precisely localized markers in a larger series of advanced tumors.

Chromosome Mapping↗
PubMed2002

Expression of heat shock protein 70 in grossly resected esophageal squamous cell carcinoma.

BACKGROUND: The aim of the present study was to use immunohistochemical methods to clarify the clinical implication of heat shock protein (HSP) 70 expression in esophageal squamous cell carcinoma and to investigate the function of HSP70 as a chaperone for p53. METHODS: Seventy-one patients with esophageal squamous cell carcinoma were admitted in the present study. Expression of HSP70 was analyzed by immunohistochemistry and correlated with TNM classification, vessel invasion, p53 expression, and clinical outcome after operation. RESULTS: Overexpression of HSP70 was related to sex (p < 0.05), tumor configuration (p < 0.05), lymph node metastasis (p < 0.01), and lymphatic vessel invasion (p < 0.05). Expression of p53 and HSP70 were not correlated with each other (p = 0.824). Esophageal squamous cell carcinoma with HSP70 expression exhibited a significantly better prognosis compared with HSP70-negative esophageal squamous cell carcinoma in univariate analysis (p < 0.05), but no significance was found in multivariate analysis. CONCLUSIONS: We suggest that HSP70 expression might be of use to assess the progression, lymph node metastasis, and lymphatic vessel invasion of esophageal squamous cell carcinoma. Inasmuch as both lymph node metastasis and HSP70 expression are prognostic variables in esophageal squamous cell carcinoma, examination of HSP70 expression may be of use to assess clinical outcome after operation.

Adult↗
PubMedDate not supplied

Anorexia athletica.

In many sports, athletes with low body weight have a distinct advantage over their opponents; however, this advantage can easily turn into a noticeable disadvantage because low body weight may also be associated with health problems. The present review focuses on the problem of anorexia athletica, with its emphasis on leanness and thinness in female and male sports athletes. Athletes often restrict calories and/or overexercise to achieve or maintain low body and fat masses. There is a growing body of evidence that several metabolic and endocrine disturbances are the result of prolonged energy restriction. However, the long-term outcome of such sport-related disordered eating has not been thoroughly studied. Effective methods of treatment are scarce and similar to treatment of eating disorders. Scientific studies are needed that help establish alternative regulations for sports in which a low body weight is a primary advantage for performance.

Adipose Tissue↗
PubMedDate not supplied

VEGF-C expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus.

Vascular endothelial growth factor C (VEGF-C) is known to act in lymphangiogenesis. Recent reports suggest VEGF-C plays a role in the spread of several cancers to the lymph system. Lymphatic spread is a critical prognostic factor in esophageal cancer, however, the molecular mechanism involved in the spread of cancerous cells remains unclear. In the present study the clinicopathological implication of VEGF-C was analyzed using immunohistochemistry. Seventy-one patients with esophageal squamous cell carcinoma (ESCC) resected in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for VEGF-C and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically. Only histological grade (differentiation) was shown to have a statistically significant correlation with VEGF-C expression (p=0.028). Age (p=0.064), lymph node metastasis (pN) (p=0.085) and vascular invasion (p=0.092) tended to correlate with VEGF-C expression although on analysis this correlation was not statistically significant. The results suggested there is no prognostic implication for VEGF-C in ESCC (p=0.80). There is no significant correlation between VEGF-C expression and clinicopathological parameters involved in lymphatic spread. However, VEGF-C expression might play an important role in metastasis of ESCC since histological grade was closely related to lymph node metastasis and distant metastasis.

Adult↗
PubMedDate not supplied

Biological analysis of gastrointestinal stromal tumors.

The biological behaviour of a gastrointestinal stromal tumor (GIST) cannot be easily predicted from preoperative clinical examination alone. As a result, there is little standardization in the surgical treatment of GIST. In this study, we analyzed the clinicopathology and immunohistochemistry of 20 cases of GIST to clarify factors associated with tumors showing malignant potential. Immunohistochemical analysis of KIT, CD34, vimentin, alpha-smooth muscle actin (SMA), s-100, p53, ki-67, bcl-2 and bax expression was performed on 20 surgically resected GIST. An apoptotic index (AI) was calculated for each sample using a TdT-mediated dUTP-biotin nick end-labeling method. With regard to bcl-2, t(14;18) translocations were also investigated using a polymerase chain reaction based method. Finally, the relationship between these biological results and clinicopathological data was analyzed. Of the 20 cases studied, two patients died due to lung or liver metastasis. All cases stained positive for vimentin, nine cases were positive for alpha-SMA and three cases positive for s-100. All cases were stained for both KIT and CD34, which tended to correlate with malignant potential. There was significant difference in frequency of bcl-2 overexpression (p<0.05) and trend in Ki-67 labeling index (p=0.098) between benign and malignant cases. However, with regard to bcl-2, no chromosomal t(14;18) translocations were detected in four analyzed cases. In GIST, overexpression of bcl-2 may play an important role in increasing malignant potential. Furthermore, Ki-67 L.I. and bcl-2 overexpression may be useful in predicting malignant potential, and therefore help to determine the surgical treatment, follow-up manner, and the necessity of adjuvant therapy.

Adult↗