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J Torhorst

Publications and source records attributed to J Torhorst.

At least 37 records · Page 2Linked to original sources
PubMed1998

Tissue microarrays for high-throughput molecular profiling of tumor specimens.

Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.

Animals↗
PubMed1998

[Initial experiences with the Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic excision of non-palpable breast lesions].

The advanced breast biopsy instrumentation (ABBI) allows the radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Forty-six patients with suspicious clusters of microcalcifications (n = 37) and with round lesions (n = 9) of the breast were investigated using the ABBI. Tissue cylinders were successfully removed in 98% of cases. No wound complications occurred and cosmesis was excellent. Histopathology revealed 35 benign (76%) and 11 malignant (24%) lesions. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.

Adult↗
PubMed1997

Altered expression of mdm-2 and its association with p53 protein status, tumor-cell-proliferation rate and prognosis in cervical neoplasia.

Recent results suggest that p53 inactivation is required for cervical-carcinoma development. The mdm-2 oncogene, which forms an auto-regulatory feedback loop with the normal p53 protein, has been found amplified in human carcinomas, thus abolishing the anti-proliferative function of p53. To investigate whether the mdm-2/p53 interaction plays a role in cervical neoplasms, we performed an immunohistochemical study in archival fixed, embedded specimens that included 178 pre-cancerous lesions (CIN) and invasive squamous-cell carcinomas of clinical stage IB. In addition to p53, we assessed the p53-associated protein, mdm-2, and the Ki-67 labelling index (LI). The presence of HPV was assessed by in situ DNA hybridization. Tumor expression of all nuclear proteins was scored as fraction of positive CIN or cancer nuclei. The analysis demonstrated a significant association of the Ki-67 LI with grade of atypia in cervical neoplasms. p53 accumulation and mdm-2 expression are higher in invasive carcinomas than in pre-cancerous lesions. No correlation was observed with HPV status. An inverse correlation was found between increased tumor-cell proliferation and mdm-2 expression in invasive carcinomas (p < 0.0001). mdm-2 expression was significantly associated with p53 accumulation (p < 0.02). However, the investigated nuclear proteins were not associated with overall survival in patients with invasive carcinomas. Cox stepwise-regression analysis revealed regional lymph node status and depth of invasion to be independent parameters.

Biomarkers, Tumor↗
PubMed1997

Angiogenesis in cervical neoplasia: microvessel quantitation in precancerous lesions and invasive carcinomas with clinicopathological correlations.

Recently, angiogenic properties have been shown in preinvasive cervical lesions. Our goal was to determine the angiogenesis in cervical intraepithelial neoplasia (CIN) and the relationship between microvessel counts, histopathological parameters, and clinical outcome in invasive cervical carcinoma. One hundred thirty-eight cervical specimens were evaluated; among these 20 were designated normal epithelium, 20 low-grade CIN, 40 high-grade CIN, and 58 invasive carcinoma. Histological sections immunostained for CD31 were quantitatively evaluated for microvessel density. The tumor proliferation rate was determined by the Ki-67 Labeling Index. Comparison of microvessel counts from normal epithelium with those from CIN and invasive carcinoma showed significant increases in precancerous lesions and invasive cancer (P < 0.0001). Microvessel density was found to be associated with the overall survival in women with invasive carcinoma (P < 0.01). There was a significant correlation of microvessel density (P < 0.05) with relapse-free survival in patients with regional lymph node metastasis. A Cox stepwise regression analysis revealed microvessel density, together with depth of invasion, regional lymph node status, and vascular invasion, to be a strong independent prognostic indicator for overall survival in patients with clinical stage IB cervical carcinoma.

Carcinoma, Squamous Cell↗
PubMed1997

DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.

Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity--found in 49.5% of the tumours--was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 +/- 10.2) than in p53-negative tumours (10.3 +/- 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Aneuploidy↗
PubMed1997

Investigation of the Bcl-2 and C-myc expression in relationship to the Ki-67 labelling index in cervical intraepithelial neoplasia.

This is the investigation of the relationship between the neoplastic cell proliferation and the expression of bcl-2 and c-myc in human papillomavirus (HPV)-negative and HPV-positive cervical intraepithelial neoplasms (CIN). The expression of bcl-2 and c-myc was studied using quantitative immunohistochemistry in 20 specimens of normal cervical squamous epithelium and 73 specimens of CIN. To analyze the neoplastic cell proliferation rate, the Ki-67 labelling index was determined; the latter was significantly different between normal epithelium and various grades of CIN (p < 0.0001). The highest proliferation rate was found in high-grade CIN. In precancerous lesions, we found the number of bcl-2 positive cells lower than in normal epithelium, but with a significant difference between low-grade and high-grade CIN (p < 0.0001). The highest percentage of bcl-2 positive neoplastic cells was found in high-grade CIN. C-myc was rarely expressed in normal epithelium. Similar to the Ki-67 labelling index, c-myc immunostaining correlated with the histological grade of CIN, with the highest percentage of c-myc positive nuclei occurring in high-grade CIN (p < 0.0001). In contrast to bcl-2 immunoreactivity, the c-myc significantly was more expressed in high-risk HPV-positive than in HPV-negative lesions. The c-myc expression in CIN is closely related to the neoplastic cell proliferation rate. With progression of intraepithelial neoplasia, bcl-2 production in neoplastic cells increases with high co-expression of c-myc.

Female↗
PubMed1997

[Breast preserving therapy of breast carcinoma: analysis of over 1,300 patients treated in the Basel region].

From 1977 to 1994 a total of 1329 breast cancer patients have been treated with breast conserving surgery in the region of Basel. This analysis is based on 832 patients treated from 1977 to 1990 according to a prospective treatment protocol, which was adjusted only once (1985). In comparison with the most known international publications this analysis represents one of the greatest homogeneous series of breast conserving treatment. We observe an overall 5-year survival of 91% and a 10-year survival rate of 77%. 94% of the women remain locally recurrence free at 5 years and 86% at 10 years respectively. At 5 years, freedom of local recurrence totals to 97% in patients without (pN0) and to 89% in patients with tumor involvement of the axillary lymph nodes (pN+) (p = 0.00008), as well as to 96% for pT1 and 91% for pT2-tumors (p = 0.08328). In our analysis the R0-resection significantly influences local recurrence free survival.

Adult↗
PubMed1996

Assessment of EGFR and TGF-alpha expression in relationship to HPV status and Ki-67 distribution in cervical intraepithelial neoplasms.

Expression of epidermal-growth-factor receptor (EGFR), transforming growth factor alpha (TGF-alpha) and Ki-67 proliferation antigen in cervical intra-epithelial neoplasms were analyzed. To examine the interrelationship of TGF-alpha, EGFR, Ki-67 and HPV status in dysplasia and carcinoma in situ, formalin-fixed tissue sections of 92 women were immunostained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The presence of HPV was assessed by in situ DNA hybridization. The highest positive TGF-alpha expression was seen in the group of mild dysplasia. The difference was significant between the relatively high expression in mild dysplasia and the low occurrence in severe dysplasia and carcinoma in situ as well. The same relation could be found between TGF-alpha expression in papilloma-virus-negative dysplasia and those with the presence of HPV 16/18. In contrast to these findings, the Ki-67 proliferation marker was intensely detectable in severe dysplasia and carcinoma in situ. Ki-67-stained neoplastic cell nuclei were found in a significantly higher percentage of HPV-positive than in HPV-negative lesions. TGF-alpha over-expression is obviously combined with low proliferating activity and vice versa. Irrespective of the grade of dysplasia or HPV status, EGFR was expressed abnormally as compared with normal squamous epithelium. Over-expression of TGF-alpha in mild dysplasia could be associated with the autocrine pathway of cell-growth regulation. In the presence of HPV 16/18 the EGFR/TGF-alpha pathway for growth stimulation is probably not involved.

Carcinoma in Situ↗
PubMed1996

Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma.

The prognosis of operated patients with non-small cell lung cancer (NSCLC) is poor despite thorough pre-operative staging. An improved preselection is needed of patients likely to profit from surgery. This study was undertaken to evaluate the prognostic significance of nuclear p53 overexpression in a cohort of 247 surgically treated patients with NSCLC. It showed that the prevalence of immunohistochemically detectable p53 overexpression varied between different tumour types. p53 overexpression was equally frequent in large cell carcinoma (53 per cent) and in squamous cell carcinoma (54 per cent), but significantly less frequent in adenocarcinoma (34 per cent; P = 0.009). p53 overexpression was particularly rare in bronchioloalveolar carcinoma (positivity in 1 of 17 cases). These variations may reflect aetiological differences between the histological subtypes. p53 overexpression was also associated with high tumour grade (P = 0.0157) and the presence of lymph node metastasis (P = 0.0259), but not with advanced tumour stage. Survival analysis showed no difference in clinical outcome between p53-positive and p53-negative tumours within 101 node-positive tumours. In contrast, survival time was significantly better in p53-negative tumours than in p53-positive tumours within the group of 113 node-negative tumours (P = 0.032). Stepwise regression analysis showed that p53 overexpression is an independent prognostic factor in node-negative NSCLC.

Biomarkers, Tumor↗
PubMed1996

Multiple primary cancers and estimation of the incidence rates and trends.

The use of different registration rules from one registry to another, both generally and also for paired organs, leads to variations in the proportion of multiple primary cancers: in men, from 0.4 to 4.9% for the colon, 0.1 to 2.7% for the lung, and 4.1 to 8.6% for the mouth and pharynx. Subjective factors, often impossible to verify, contribute to these variations. The impact on the estimation of incidence rates and trends is not negligible for cancers of the mouth and the pharynx and for all the cancers taken together. The trend towards an increase of cancers of the mouth and pharynx in the Bas-Rhin disappeared when the incidence was expressed taking only the first cancer (incidence by individual) into consideration, and the differences in incidence between the Calvados and the Bas-Rhin registries for the same site also disappeared. In the absence of harmonisation of the rules and methods followed for registration, incidence by individual is the only approach which makes it possible to compare incidence rates and trends between registries.

Breast Neoplasms↗
PubMed1996

BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Germline mutations in the BRCA1 gene have been associated with familial breast/ ovarian cancer in large families showing high penetrance of the disease. Little is known, however, about the contribution of BRCA1 mutations to breast/ovarian cancer in small families with few affected members or in isolated early onset cases. Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients who either came from small families with as few as one affected first degree relative, or in patients who had no family history but had developed breast cancer under 40 years of age. Using the protein truncation test, we were able to identify three unique BRCA1 germline mutations (4.8%). Two of the probands had only one affected first degree and several second degree relatives and the third had three affected first degree relatives including two sisters who, when tested, were also found to carry the mutation. There was no family history of ovarian cancer in any of the three families.

Adult↗
PubMed1996

[Latissimus dorsi for autologous volume substitution in defects after breast saving therapy].

The present paper is based on the prospective data on breast conserving therapy recorded since 1977 in the "Basel protocol". Here both surgical and radio-oncological procedures are standardized, and a form sheet is provided for registering the pathological findings. Since our data showed that local recurrence free survival of patients treated by tumor resection only just in sano or questionably in sano was statistically significantly worse, it was decided to fill the volume defect occurring during breast conserving therapy with autologous tissue, in selected cases. Also an adjuvant radiation therapy was performed. Since January. 1st, 1992 we performed volume substitution by a latissimus dorsi flap in 27 patients treated by a surgically "enlarged" breast conserving concept. A classical skin muscle island, a deepithelized skin muscle island or a mere muscle island flap were performed. Aim of this pilot study was to further optimize early and late cosmetic results, to enlarge indication for breast conserving therapy and improve loco-regional tumor control.

Adult↗
PubMed1995

Detection of new mutations in six out of 10 Swiss HNPCC families by genomic sequencing of the hMSH2 and hMLH1 genes.

The cancer predisposition in most HNPCC families is believed to be associated with mutations in the human mismatch repair gene homologues hMSH2 and hMLH1. We searched for mutations in our collection of 10 Swiss HNPCC families by sequencing the exons and exon/intron boundaries of the hMSH2 and hMLH1 genes. In four families we found different mutations which are expected to lead to protein truncations of either the hMSH2 or the hMLH1 proteins owing to premature in frame stop codons or splice defects. In two more families we detected mutations leading to an amino acid deletion and an amino acid substitution in an evolutionary conserved residues respectively. None of these mutations has been reported in other families, which is consistent with the notion that HNPCC associated hMSH2 and hMLH1 mutations are heterogeneous and there is no striking founder effect in the Swiss population. Whenever this could be investigated, the presence of the mutations was confirmed in other family members who showed manifestations of HNPCC. Interestingly, an obligate carrier in one of the families developed a brain tumour at the age of 29, histologically verified as a glioblastoma multiforme, which was recently linked to HNPCC in the context of Turcot's syndrome.

Adenocarcinoma, Mucinous↗
PubMed1994

[Results following resection in early stomach carcinoma].

The results of surgical resection in early gastric cancer were analyzed retrospectively. These operations were performed between 1982 and 1991 on 52 consecutive patients (29 women, 23 men; average age 64 [35-85] years). The tumours were resected by total gastrectomy in 11, by subtotal gastrectomy in 31, and by Billroth I resection in 10, followed by limited lymphadenectomy of the perigastric group of lymph-nodes (D1 dissection). There was one operative death (1.9%). The tumor was confined to the mucosa in 36 patients (69%), while submucosal infiltration was present in 16 (31%) and metastases to the regional lymph-nodes in seven (13%). Follow-up examination took place in all patients, after an average period of observation of 6.1 years. For the total group the 5-year survival rate, including operative mortality, was 83.7%. It correlated with the depth of penetration of the tumour and nodal involvement. 5-year survival rate for mucosal tumour was 90%, with submucosal infiltration 66.7% (P < 0.03), without lymph-node metastasis 86.4%, with it 68.6% (P < 0.05). The extent of resection and the tumour classification (according to Laurén--intestinal or diffuse) did not influence survival.--Early gastric cancer, contrary to that in the advanced stages, has a very good prognosis. But it is significantly altered by the depth of penetration of the tumour and nodal metastasis.

Adult↗
PubMed1994

Estimating the incidence of cancers in Switzerland: 1983-1987.

Estimates have recently been made of the incidence of cancers in the countries of the European Community. Similar estimates are given for Switzerland, based on data from the six Swiss cantonal cancer registries, all of which have been operating for at least 12 years. These registries cover Basel, Geneva, Neuchatel, St Gall and Appenzell, Vaud and Zurich, which account for about 50% of the Swiss population as a whole. Two different methods were used to extrapolate from the incidences observed in the regions covered by cancer registration to the entire country. The first method is based solely on the distribution of populations according to the country's main linguistic groups, whereas the second relies on mortality data. Estimates obtained by the second approach are presented and their reliability is discussed. Comparison of the age incidence curve with that of Denmark tends to confirm the validity of the estimations. Estimated standardised rates (world population) for all sites except nonmelanomatous skin cancer are 294.3 for males and 214.2 for females. Comparisons with other European countries show that in males, lung cancer is relatively less common in Switzerland, whereas in females, breast cancer is relatively more frequent.

Adolescent↗
PubMed1993

[Familial incidence of colorectal carcinoma and its significance for a screening program (the example of Upper Basel area)].

Primary prevention of colorectal carcinoma aims at interruption of the adenoma-carcinoma sequence. Colonoscopy is the most reliable screening method, but up to now has only been recommended for persons at high risk. The ongoing 10-year study defines a possible risk group and determines the efficacy of a preventive screening program based on family history. This paper reports on the descriptive statistics of the first five years. All patients with colonic carcinoma diagnosed between 1987 and 1991 living in the upper part of Canton Basel-Land were registered. According to the family history, patients with at least one first degree relative with colonic carcinoma were defined as index patients. Their first degree relatives entered a prospective screening program which includes colonoscopy. 230 colonic carcinomas were diagnosed in the upper part of Basel-Land, representing an incidence of 48/year/100,000 persons. They included 3 (1.3%) hereditary and 227 (98.7%) sporadic carcinomas. 23 (10%) patients had a positive family history. These patients defined 94 relatives at risk. The incidence of colonic carcinoma in the Canton studied does not differ from that reported in Switzerland. Therefore, this part of Basel-Land can be considered representative. The 1.3% hereditary carcinomas are in contrast to the published data of 6%.

Adenomatous Polyposis Coli↗