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L Skoog

Publications and source records attributed to L Skoog.

At least 73 records · Page 4Linked to original sources

c-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer.

Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

p53 expression and the result of adjuvant therapy of breast cancer.

Functional p53 protein is essential for the cellular response to drug-induced DNA damage. We investigated p53 accumulation in tumour specimens from premenopausal breast cancer patients who were randomised to adjuvant chemotherapy (CMF) or postoperative radiotherapy. Of the tumours from 139 patients, 20 showed abnormal accumulation as judged with immunohistochemistry (> 10% positive tumour cells). The risk of distant recurrence was similar in the two treatment groups for patients whose primary tumours lacked p53 accumulation, whereas there was a significant benefit from CMF for patients showing abnormal accumulation (relative risk 0.18, 95% CI, 0.04-0.93). This result suggests that p53-dependent apoptosis is not a general mechanism by which breast cancer cells respond during CMF chemotherapy.

Aneuploidy↗

Nonrandom numerical aberrations of chromosomes 7, 9, and 10 in DNA-diploid bladder cancer.

Double-target in situ hybridization technique (ISH) was applied to 37 cases of bladder cancer to detect numerical aberrations of chromosomes 7, 9, 10, and 11 by centromeric DNA probes. Of 33 evaluable cases, 29 (88%) demonstrated chromosome aberrations. In 17 cases with diploid pattern as measured by flow-cytometric DNA analysis (FCM), 15 (88%) demonstrated chromosome aberrations. Of these, trisomy 7, monosomy 9, and trisomy 10 were detected in three, three, and one case, respectively, as a single chromosome aberration. In 14 (88%) of 16 cases with an aneuploid DNA pattern, chromosome aberrations for two or more chromosomes were demonstrated. A significant correlation was observed between grade of chromosome aberrations and tumor grade (p < 0.01, Fisher's test), between number of spots for chromosome 7 and peak value in FCM (p = 0.015, by Spearman rank order test). In eight cases, chromosome aberrations in the tumor were compared with the corresponding pattern in the grossly normal and histologically benign mucosa. Trisomy 10 and monosomy 9 were detected as chromosome numerical aberrations in the histologically normal mucosa, consistent with aberrations in the corresponding patients. We conclude that trisomy 7, monosomy 9, and trisomy 10 may be early events in the evolution of bladder cancer.

Carcinoma, Transitional Cell↗

Loss of heterozygosity studies in tumors from families with breast-ovarian cancer syndrome.

A gene (BRCA1) predisposing for familial breast and ovarian cancer has been mapped to chromosome band 17q12-21. Based on the observation that ovarian tumors from families with breast and ovarian cancer lose the wild-type allele in the region for the BRCA1 locus, it has been suggested that the gene functions as a tumor suppressor gene. We have studied chromosomal deletions in the BRCA1 region in seven breast tumors, three ovarian tumors, one bladder cancer, and one colon cancer from patients in six families with breast-ovarian cancer, in order to test the hypothesis of the tumor suppressor mechanism at this locus. We have found a low frequency of loss of heterozygosity at this region, and our results do not support the idea that BRCA1 is a tumor suppressor gene. Alternatively, the disease segregating in these families is linked to one or more different loci.

Breast Neoplasms↗

S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer.

Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post-operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07-0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours.

Breast Neoplasms↗

Thyroid peroxidase immunodetection as a tool to assist diagnosis of thyroid nodules on fine-needle aspiration biopsy.

In a previous work we have reported the presence in 96.9% of malignant and 4.2% of benign thyroid tumors of an immunological abnormality of the enzyme thyroid peroxidase, impeding the fixation of the anti-thyroid peroxidase monoclonal antibody termed "MoAb47". The present study has been designed to establish the ability of thyroid peroxidase immunodetection to assist the diagnosis of malignancy in fine-needle aspiration of thyroid nodules. The fixation of anti-thyroid peroxidase monoclonal antibody was investigated by immunohistochemistry on fine-needle aspirates of 150 surgically removed thyroid nodules (20 papillary carcinomas, five follicular carcinomas, 90 colloid adenomas, nine fetal adenoma, 13 atypical adenomas, five oncocytic adenomas, six Hashimoto's thyroiditis and two Graves' disease). The percentage of positive cells has been compared to the final histological diagnosis. In samples from 113/125 benign nodules 80-100% cells presented a positive immunoreaction, whereas all samples from malignant tumors yielded less than 80% positive cells. Benign nodules exhibiting less than 80% positive cells corresponded to three degenerative colloid nodules, five atypical follicular adenomas, two oncocytomas and two thyroiditis. According to results obtained in this series, with the value of 80% as the limit for discrimination between benign and high-risk nodules, the sensitivity of thyroid peroxidase staining for diagnosis of malignancy would be 100%, its specificity 90% and its overall accuracy 92%. Thyroid peroxidase staining with monoclonal antibody MoAb47 on fine-needle aspirates is a useful adjunct to conventional cytology for the investigation of patients with thyroid nodules.

Biopsy, Needle↗

The general mammography screening program in Stockholm. Organisation and first-round results.

This presentation describes the organization and first-round results of the Stockholm mass mammography screening program, and discusses ways of checking the quality of an ongoing screening program. The Stockholm mammography screening program started in 1989 at five independent screening units, and comprises more than 150,000 women aged 50 to 69 years. The first round was completed in June 1991. Compliance during the studied period was 70.6%, and the recall rate was 3.0% of the attending women. Breast cancer was diagnosed in 676 women, of whom 90 (13.3%) had a cancer in situ. The cancer prevalence rate was thus 6.3 cancers per 1,000 screened women. Surgery was performed on 925 women, of whom 249 had benign lesions, giving a benign/malignant ratio of 0.37 to 1. Fifty-two per cent of the cancer patients were operated with breast conserving surgery. The median size of the invasive cancers was 12 mm; almost 80% were node-negative. Experience from the first two years of this mass mammography screening program shows that it meets the major quality requirements. One of the main future goals is to maintain the high quality of the program. Another important goal is a further increase in compliance.

Aged↗

Relationship of DNA ploidy and S-phase fraction to survival after first recurrence of breast cancer.

Flow cytometry was performed on frozen specimens from the primary tumour of 184 women with recurrent breast cancer. No significant association was seen between DNA ploidy and the other prognostic factors investigated. Patients with a high S-phase fraction had more often a negative estrogen receptor (ER) status and a short disease-free interval. A shorter survival after disease recurrence was seen both in patients with DNA aneuploid tumours and among those with a high S-phase fraction. Patients with DNA tetraploid tumours showed the longest survival after recurrence. In this subgroup, half of the patients survived more than 3 years after recurrence and the estimated survival rate at 10 years was 17%. In a Cox's regression analysis including 116 patients, site of recurrence, number of positive nodes at time of primary operation, size and ER content of the primary tumour as well as DNA ploidy showed additional prognostic value.

Breast Neoplasms↗

Fine needle aspiration biopsy for diagnosis and follow-up of prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

Fine needle aspiration biopsy (FNAB) and ultrasound-guided core biopsy using biopty gun both have a high, and approximately equal, accuracy in diagnosing and grading prostate cancer. The TRUS-guided technique provides a better estimation of the tumor extent and to some degree even of capsular involvement. It is therefore a recommendable part of the preoperative evaluation when radical prostatectomy is contemplated. On the other hand, the aspiration technique usually provides more epithelial cells. It entails a significantly lower risk of septic complications and of seeding tumor cells. It has also a lower cost than the core biopsies. The aspiration biopsy can easily be performed repeatedly in the follow-up procedure, which is of particular importance in cases managed with watchful waiting. We recommend the aspiration biopsy for routine use in the diagnostic work-up and follow-up. It is essential that not only the cytologic evaluation but as well the sampling from the prostate is performed with adequate expertise.

Biopsy, Needle↗

Genetic rearrangements in sporadic and familial gastric carcinomas detected with microsatellite markers.

Ten gastric carcinomas were studied for loss of heterozygosity by analysis of 21 microsatellite markers from 14 different chromosomes. Four patients had a family history of gastro-intestinal cancer, and six tumours were considered sporadic. We also studied a new mechanism in tumourigenesis recently reported in hereditary non polyposis colon cancer, a defect in mismatch repair that is seen as gain of new bands by the use of dinucleotide repeat markers. Loss of heterozygosity was detected with two markers in one primary tumour and with the majority of markers in one metastasis from a sporadic gastric tumour. Gain of microsatellite bands was seen in one tumour from a gene carrier in a family with hereditary non-polyposis colon cancer and in one sporadic tumour. Two tumours from patients with a family history of gastric cancer showed no rearrangements. Our results suggest that different types of genes are involved in initiation and progression of gastric cancer in sporadic and familial gastric cancer.

Adult↗

Deletion mapping of chromosome 8p in prostate cancer by fluorescence in situ hybridization.

Double-target fluorescence in situ hybridization (FISH) was applied to 42 cases of prostate cancer and seven cases of histologically proven benign prostate hyperplasia for the detection of structural aberrations of chromosome 8. Cosmid probes for two chromosome 8p loci (LPL/8p22 and D8S7/8p23) were used in 34 specimens of malignant tumors obtained by the touch biopsy technique. Deletion was defined as when the number of cosmid signals was lower than the number of centromere signals in more than 35% of all nuclei observed. In total, thirty of the 42 (71%) specimens demonstrated any type of 8p deletion. Out of the 34 cases in which deletion mapping could be evaluated, distal deletion (D8S7) was detected in 17 (50%), of which 10 also showed deletion of LPL. Deletion of LPL was detected in 18 cases (53%), of which 8 (24%) retained the D8S7 (interstitial deletion). When the deletion pattern was graded as (1) no deletion (2) partial deletion (either D8S7 or LPL deleted) and (3) both deletions, the degree of deletion was well correlated with the tumor grade (P = 0.0009) and with stage (P = 0.0072, Fisher's Exact test). These data support the hypothesis that tumor suppressor gene(s) may be located in the chromosomal region 8p22, hence 8p deletions may play a crucial role in the pathogenesis of prostate cancer.

Chromosome Deletion↗

Loss of heterozygosity in familial breast carcinomas.

Three loci have been implicated in the etiology of familial breast cancer; the BRCA1 locus on 17q, the p53 gene on 17p, and the androgen receptor gene on the X chromosome. However, it has been estimated that in approximately 50% of all breast cancer families the predisposing genetic defect is not linked to any of these three loci. In an attempt to identify chromosomal regions harboring putative breast cancer genes we performed allelotyping in 82 familial breast carcinomas. Polymorphic markers representing 45 different loci were analyzed and the most frequently involved chromosomal arms were 8p, 16q, 17p, 17q, and 19p.

Adult↗

Deletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases.

Genetic alterations that occur in human breast cancers are believed to be of importance for initiation as well as progression of the disease. In order to find a genetic alteration that may be used as a prognostic marker, 82 familial breast carcinomas were analyzed for loss of constitutional heterozygosity at polymorphic loci on all chromosomes. Frequently occurring allele losses were compared to estrogen receptor expression, lymph node metastases, tumor size at the time of operation, and distant metastases at the time of follow-up 2-15 years later. Loss of heterozygosity (LOH) on the long arm of chromosome 16 in the tumor at the time of operation was significantly correlated (P < 0.001) with the occurrence of distant metastases 1-13 years after the operation. In addition, LOH at 16q was not correlated with estrogen receptor status, lymph node positivity, or tumor size, nor was the occurrence of distant metastases correlated with any of these parameters. The results suggest the existence of a tumor suppressor gene on 16q that facilitates hematogenic spread of breast cancer and that LOH at this locus is an independent prognostic marker in breast cancer.

Breast Neoplasms↗

Adenoid cystic carcinoma of the breast: diagnosis by fine-needle aspiration.

Adenoid cystic carcinoma rarely occurs as a primary breast malignancy. When seen in fine-needle aspiration (FNA) material, it is identical to its counterpart in the salivary glands. We report six cases diagnosed by aspiration in patients aged 32-82 yr. The smears were highly cellular and featured extracellular spheres of metachromatic material. These were surrounded by small, uniform cells with bland nuclei and very little cytoplasm. Numerous similar cells occurred singly in the background. The cytologic differential diagnosis of adenoid cystic carcinoma includes other entities that produce extracellular metachromatic spheres including collagenous spherulosis. We describe and illustrate similar material originating in inspissated secretions or stromal fragments from fibrocystic change and fibroadenoma, as well as infiltrating ductal carcinoma. Diagnostic criteria for adenoid cystic carcinoma and the clinical relevance of distinguishing this rare tumor from typical infiltrating ductal carcinoma are discussed.

Adult↗

Nodular fasciitis: spontaneous resolution following diagnosis by fine-needle aspiration.

Nodular fasciitis can be histologically mistaken for a sarcoma. Typical cases are less than 5 cm and enlarge rapidly over days or weeks before diagnosis. The natural history of nodular fasciitis is unknown, since the diagnosis is usually based on excised lesions. Fine-needle aspiration of nodular fasciitis has been described, and features benign-appearing spindle cells (singly and in groups), collagen, and myxoid material. We describe 11 cases in which nonsurgical observation led spontaneously to complete resolution. Our study includes 7 males and 4 females (24 to 73 years of age; median = 42). Lesions were located in the arm (4), thigh (3), temporal area (2), breast (1) and the parotid (1) and ranged from 0.5 to 5.0 cm. (median = 1.5). They had been present for from less than 1 to 4 weeks (median = 2). In 9 cases, spontaneous resolution occurred in from 3 to 8 weeks (median = 4). Two other patients were lost to follow-up for up to 11 months, after which resolution was noted. Small palpable masses in the subcutaneous soft tissues which evolve over a short period of time and show the cytologic features of nodular fasciitis should be managed nonsurgically. If resolution does not occur within a few weeks, surgery can then be performed.

Adult↗

Four separate regions on chromosome 17 show loss of heterozygosity in familial breast carcinomas.

Two genes predisposing females to autosomal dominant breast cancer are located on chromosome 17. Mutations in the p53-gene on the short arm have been shown to predispose females to early onset breast cancer in families with the rare Li-Fraumeni syndrome. Another locus on 17q (BRCA1), was found to be linked to the disease in a subset of families with breast cancer. In order to determine the involvement of tumour suppressor genes at these loci in tumour development, we studied allele losses for markers on chromosome 17 in 78 familial breast carcinomas. The analysis used six polymorphic DNA markers, three on each arm. We found support for at least four separate regions displaying allele losses on chromosome 17: the p53-region, the distal part of 17p, the BRCA1 region and the distal part of 17q. The frequency of allele losses on distal 17p (16%) is low in these familial tumours compared with the previously reported incidence in sporadic tumours (> 50%), whereas the frequency of losses at the p53 locus and on 17q was similar to sporadic tumours (5%-40%). These data suggest that several regions on chromosomal 17 can harbour tumour suppressor genes involved in tumour development of familial breast cancer.

Alleles↗

Lack of correlation between anxiety parameters and oestrogen receptor status in early breast cancer.

Correlation between anxiety parameters and oestrogen receptor levels (ER) were investigated in 89 patients with primary breast cancer. Patients were divided into two groups, ER poor (< 0.05 fmol/microgram DNA) and ER rich (> 0.05 fmol/microgram DNA). No differences were found between anxiety levels, determined by a modified Hospital Anxiety and Depression (HAD) scale, in the two groups. This report does not support the findings from other studies, claiming an association between psychological parameters and oestrogen receptor status, which is believed to be a prognostic predictor.

Adult↗