Biomedical subjects

E Munck-Wikland

Publications and source records attributed to E Munck-Wikland.

At least 19 recordsLinked to original sources

PubMed2001

Outcome of ipsilateral treatment for patients with metastases to neck nodes of unknown origin.

It is not uncommon for head and neck cancer patients to present with neck node metastases. Standard treatment for patients in whom no primary tumor is found include surgery and radiotherapy but there is still controversy about the type and extent of treatment. A retrospective review was carried out on 51 consecutive patients with cervical lymph node metastases of unknown origin, treated between 1980 and 1994 at Radiumhemmet, Karolinska Hospital. All patients received radiotherapy to the ipsilateral neck and the corresponding mucosa and surgery was performed in 55% of cases. The 5-year overall survival rate was 41%. A primary tumor was later found in 6 cases (12%). Two cases of cancer were detected after 5 years and classified as 'second primaries'. Results from this small retrospective material have to be interpreted with caution but indicate that limited, ipsilateral radiotherapy to mucosa and lymph nodes combined with surgery, when possible, may be justified.

Adult↗

PubMed2000

Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival.

Human papillomavirus (HPV) is more commonly found in tonsillar cancer than in other head and neck cancers. The importance of HPV status in tonsillar cancer for prognosis remains unclear. The aim of the present study was to investigate the frequency of HPV in tonsillar cancer and to correlate the presence of HPV with tumor stage, nodal status, grade of differentiation, risk of relapse, and survival. HPV DNA and HPV type were determined, using PCR, in pre-treatment biopsies from 60 cases of primary tonsillar cancer. All patients had undergone full-dose radiotherapy, 45% as the only treatment modality, and 55% in combination with surgery. HPV 16 was detected in 43% (26/60) of the cancers including 1 double infection of both HPV 16 and HPV 33. Patients with HPV(+) tonsillar cancer showed less risk of relapse within 3 years after diagnosis, with a better odds ratio of 4.18 as compared with HPV(-) patients (p = 0. 025). Furthermore, cause specific survival was significantly (p = 0. 047) better in patients with HPV(+) tonsillar carcinomas. At 3 years after diagnosis the survival rate was 65.3% in the HPV(+) group and 31.5% in the HPV(-) group, and at 5 years the survival rate was 53. 5% and 31.5%, respectively. The better outcome for patients with HPV(+) tonsillar cancer was independent of TNM stage, nodal status, gender and age. These results indicate that HPV status is a significantly favorable prognostic factor in tonsillar cancer and may be used as a marker in order to optimize the treatment of patients with this type of cancer.

Adult↗

PubMed1999

Prognostic impact of complete remission after preoperative irradiation of tonsillar carcinoma: a retrospective analysis of the radiumhemmet data, 1980-1995.

PURPOSE: This retrospective study was done to determine the outcome of patients with tonsillar carcinoma treated at Radiumhemmet, Karolinska Hospital, between January 1980 and December 1995 with radiotherapy alone or in combination with surgery. In addition the importance of tumor remission for patient survival was analyzed. METHODS AND MATERIALS: The analysis is based on 167 previously untreated patients with biopsy-proven, invasive tonsillar squamous cell carcinoma of the tonsillar region. All patients were consecutively admitted to the Department of General Oncology, Radiumhemmet, and treated with curative intent. The median follow-up time was 20 months. The median target dose was 64 Gy, delivered in fractions of 2 Gy 5 times weekly. Twenty-eight percent of the patients underwent surgery of the primary site and/or neck dissection after radiotherapy (RT). RESULTS: The overall local control rate for the whole patient group after radiotherapy was 79%. Probability of survival after 5 years for patients responding with complete remission (CR) was 43% and for patients with incomplete response (non-CR) 9%, (p<0.0001). The survival in the non-CR group treated with combination therapy was 20 months longer than in patients receiving radiotherapy alone (p<0.0001). There was no statistically significant difference in prediction of long-term survival when the patient population was stratified according to tumor differentiation grade, age, sex, nodal status, or treatment time. CONCLUSION: The strongest clinical predictor of survival was the degree of tumor remission after RT. For the non-CR group receiving combination treatment including surgery there was a survival benefit as compared to patients treated with RT alone (p<0.0001) although there were few long-term survivors in this patient group.

Carcinoma, Squamous Cell↗

PubMed1999

Predictive value of malignancy grading systems, DNA content, p53, and angiogenesis for stage I tongue carcinomas.

AIM: To assess the clinical value of malignancy grading systems compared with nuclear DNA content, protein p53, and angiogenesis for predicting recurrence of stage I (UICC, 1987) tongue carcinomas. METHODS: Histopathological malignancy grading according to Jakobsson and tumour front grading according to Bryne et al were performed on haematoxylin and eosin slides. DNA analysis was performed by image cytometry. Protein p53 and angiogenesis were evaluated by immunohistochemical analysis using antibody CM1 and antibody against factor VIII related antigen, respectively. RESULTS: 49 patients with stage I carcinomas of the mobile tongue were included, all treated by local surgical excision alone. Eight patients (16%) suffered from local recurrence during follow up, and 13 (27%) had regional recurrence. Both Jakobsson's malignancy grading system and p53 immunoreactivity proved to be useful predictors of regional recurrence in a Cox multivariate regression analysis. CONCLUSIONS: Histopathological malignancy grading systems provide valuable prognostic information and can still compete with current biological markers in this respect.

Adult↗

PubMed1998

Evaluation of tissue and serum VEGF in patients with head and neck carcinoma.

Serum vascular endothelial growth factor (VEGF) was measured in 54 cancer patients with head and neck carcinoma. In addition, tumor VEGF was examined by immunohistochemistry in sections of biopsies obtained within 4 weeks to serum sampling in 37 of these patients. Serum VEGF levels were higher in the sera of the tumor patients than in the sera of healthy control subjects (P < 0.005). Patients with stage II-IV tumors showed increased levels of serum VEGF, whereas patients with stage I tumors did not. The receiver operating characteristics (ROC) of serum VEGF were similar to those observed with TPS (tissue protein specific antigen). Immunohistochemistry of tissue sections showed that 24/37 tumors were VEGF positive. No connection was observed between strong VEGF staining of tumor tissue sections and high levels of serum VEGF. We conclude that serum VEGF could be a useful marker for monitoring head and neck carcinoma patients, but that serum and tissue VEGF levels do not appear to correlate with each other.

Journal Article↗

PubMed1998

Nuclear DNA content and p53 overexpression in stage I squamous cell carcinoma of the tongue compared with advanced tongue carcinomas.

AIMS: To evaluate the predictive value of the nuclear DNA content (image cytometry) and p53 overexpression (immuno-histochemistry using antibody CM-1) in uniformly treated stage I carcinomas of the mobile tongue. Also, to compare stage I carcinomas with advanced tongue carcinomas (stages II-IV). METHODS: Archival formalin fixed, paraffin wax embedded tumour specimens from 54 patients with stage I squamous cell carcinoma and 37 patients with advanced squamous cell carcinoma were analysed. Mean follow up time of the stage I carcinomas was 71 months (median, 62.5; range, 6-175). RESULTS: Twenty three patients (stage I) had recurring disease: 10 had local recurrence (in the tongue) and 13 had regional recurrence (cervical metastases). Locally recurring stage I carcinomas had a more pronounced DNA deviation than the other stage I carcinomas and this degree of deviation was comparable with the DNA content of advanced carcinomas. Stage I carcinomas that developed regional recurrences overexpressed p53 more frequently. In Cox multivariate regression analysis of time to recurrence, DNA deviation was a significant parameter in tumours that recurred locally (p = 0.032). p53 overexpression was the only parameter close to significance for regional recurrence (p = 0.065). CONCLUSIONS: Nuclear DNA content and p53 immunostaining are of value for the prediction of recurrence of stage I squamous cell carcinomas of the mobile tongue. Stage I tongue carcinomas that are prone to local recurrence show the same DNA content as do advanced tongue carcinomas.

Adult↗

PubMed1998

Stromelysin-3 mRNA expression in dysplasias and invasive epithelial cancer of the larynx.

Matrix metalloproteinases are believed to play an important role in tumor progression, invasion and metastasis. In order to investigate if the expression of stromelysin-3 (ST3) mRNA could add prognostic information concerning invasive laryngeal cancer and/or be indicative of a high risk for tumor progression in laryngeal dysplasias ST3 expression was analyzed by in situ hybridisation of formalin fixed paraffin embedded laryngeal specimens. Furthermore, all specimens underwent image cytometry (ICM) DNA analysis, and, p53 immunostaining. Invasive epithelial cancer, both localized (T1, T2) cancers, cured, as well as not cured, by radiotherapy, and cases with regional lymph node metastases were studied. Furthermore, high grade and low grade dysplasias, selected for rapid, slow and non-progression, as well as non-neoplastic inflammatory lesions were investigated. Expression of the ST3 gene was found in 9 out of 14 (64%) invasive cancer lesions, and in 3 out of 10 (30%) dysplasias, thus indicating that ST3 expression correlates to tumor progression. The ST3 positive laryngeal cancer lesions displayed a higher degree of DNA aberration than the ST3 negative lesions thus suggesting that ST3 positivity could indicate highly malignant tumors. Of the three ST3 positive dysplasias, the first progressed rapidly to cancer in situ with suspected microinvasion. The second ST3 positive dysplasia progressed to invasive cancer within five months. The third ST3 positive dysplasia had been radically excised and hereby cured. All but one of the dysplastic lesions showed p53 immunoreactivity, and all dysplasias exhibited aneuploid cells. ST3 expression appears to be a late event in the multistage process of carcinogenesis and could prove useful as an indicator of dysplasias with imminent risk for progression to invasive cancer.

Humans↗

PubMed1997

p53 immunostaining and image cytometry DNA analysis in precancerous and cancerous squamous epithelial lesions of the larynx.

BACKGROUND: Squamous epithelial cancer can develop from progressive epithelial changes connoted dysplasias. Histopathologic evaluation/grading of these lesions is difficult and gives poor information concerning the risk for progression to cancer. Squamous cell carcinoma of the head and neck (SCCHN) frequently show p53 alteration and DNA-ploidy aberration. Could these markers be used as indicators for malignancy risk in the larynx? METHODS: Immunohistochemical staining (IHC), with the CM-1 antibody against p53, and image cytometry (ICM) DNA analysis were performed in 60 lesions from 12 patients--and 21 controls--who were initially seen with laryngeal lesions prior to cancer in situ (cis) or invasive cancer diagnosis at the same site. RESULTS: All but one of the invasive cancers, and 77% of the lesions which preceded cancer or cancer in situ, showed positive p53 immunostaining, as compared with only 10% of the controls. All but one of the invasive cancer lesions, and 77% of the precancerous lesions, showed aberrant DNA-ploidy results, whereas all controls were diploid. When DNA and p53 analysis were combined, only one of the lesions preceding cis or invasive cancer was negative. CONCLUSIONS: Both p53 immunoreactivity and DNA-ploidy aberration appear to be early events in the multistep process of squamous epithelial carcinogenesis. Immunohistochemical staining p53 analysis and ICM DNA analysis does increase the diagnostic sensitivity for cancerous and true precancerous lesions in the larynx.

Adult↗

PubMed1996

Pseudomonas aeruginosa in otitis externa. A particular variety of the bacteria?

BACKGROUND: Pseudomonas aeruginosa rarely affects the epithelium in healthy persons except for the external ear canal, raising the possibility that P aeruginosa in otitis externa is a specific variety that displays particular characteristics. DESIGN: A cohort study was designed to outline distinct characteristics of P aeruginosa in otitis externa compared with P aeruginosa in other infections. The study period was October 1, 1994, to March 27, 1995. PATIENTS: Isolates of P aeruginosa from nonhospitalized patients were collected at the bacteriological laboratory at Karolinska Hospital, Stockholm, Sweden; there were 53 strains of P aeruginosa isolated from otitis externa and 59 strains of P aeruginosa from varicose ulcers and urinary tract infections. METHODS: Pseudomonas aeruginosa was characterized by pigmentation, growth habits, production of mucoid, and biochemical characteristics. RESULTS: Pseudomonas aeruginosa in otitis externa produced less pyocyanin and less urease and exhibited no mucoid-producing strains. CONCLUSIONS: Pseudomonas aeruginosa in otitis externa displayed fewer of the usual biochemical features of the species than did the strains isolated from other infections. Some of these features, such as the production of pyocyanin, are influenced by nutritional factors; strains found in otitis externa probably represent the type of strains present in the natural habitat in water, as opposed to the strains that have adapted to the environment of other human infections. Increased knowledge of the characteristics of the strains found in otitis externa is important in understanding the pathogenesis of the disease and why P aeruginosa is the dominant infectious agent in otitis externa.

Humans↗

PubMed1995

Interferon-alpha/beta can impede development of carcinogen-induced squamous-cell tumors in the esophagus of C57B1 mice.

The effect of treatment with murine interferon-alpha/beta preparations on diethylnitrosamine-induced squamous-cell tumors in the esophagus of C57B1 mice was investigated. Diethylnitrosamine was administered in the drinking water for 18 weeks. Interferon was given intraperitoneally during the same 18 weeks or from the end of the period of carcinogen exposure until termination of the experiment. In mice given interferon and diethylnitrosamine synchronously, a significantly lower tumor index (number of tumors/cm of esophageal mucosa) was observed as compared to all control groups. Treatment with interferon after the administration of the carcinogen was terminated had no effect on the appearance of tumors. These data suggest that interferon therapy can exert certain effects on carcinogenesis.

Animals↗

PubMed1995

Altered p53 in microdissected, metachronous, premalignant and malignant oral lesions from the same patients.

Aims-To determine whether mutant p53 alleles harboured by malignant tumours of the oral cavity were also present in previous premalignant lesions at the same site.Methods-Paraffin embedded tumour specimens along with their premalignant counterparts were analysed for p53 alterations using immunohistochemistry, microdissection, polymerase chain reaction amplification, and DNA sequencing.Results-Malignant lesions from five of eight patients showed overexpression of p53 protein by immunohistochemistry. Upon DNA sequencing, two of these five specimens had p53 mutations. Of the five patients whose cancers showed p53 overexpression by immunohistochemistry, three had previous premalignant lesions that also had immunohistochemically detectable p53 protein. However, DNA sequencing showed that none of these three had mutations in the p53 gene. The remaining five premalignant lesions had no immunohistochemically detectable p53 protein.Conclusions-Some premalignant lesions have increased p53 protein which can be detected by staining with antibody to p53. This staining is not caused by mutations in p53 that are found in subsequent tumours at the same site.

Journal Article↗

PubMed1994

Nuclear DNA content, proliferating-cell nuclear antigen (PCNA) and p53 immunostaining in predicting progression of laryngeal cancer in situ lesions.

Squamous epithelial cancer in situ (CIS) of the upper aerodigastric tract is a histopathologically well-defined condition. However, in clinical practice, morphological grading of dysplasia is difficult and shows large variability. The biology of CIS remains enigmatic, and there is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed image DNA cytometry (ICM) and immunohistochemical staining for PCNA as well as p53 in 38 laryngeal CIS lesions, of which 9 progressed to invasive cancer. The majority of the CIS lesions displayed high-grade DNA aberration, a high PCNA-positive rate, and every third lesion was p53-positive by immunostaining. The lesions which progressed to invasive cancer showed a clear tendency towards more pronounced DNA aberration, a higher percentage of intense PCNA staining and more frequent p53 positivity. By combining the results from the analyses of DNA, PCNA and p53 in a prognostic index for each individual case, we correctly classified 82% of the lesions as progressors or non-progressors.

Adult↗

PubMed1994

The relationship between aneuploidy and p53 overexpression during genesis of colorectal adenocarcinoma.

This paper describes the investigation of nuclear DNA content and p53 immunoreactivity in normal mucosa (n = 25), mildly (n = 15), moderately (n = 28) and severely atypical (n = 22) colorectal adenomas and in colorectal adenocarcinomas (n = 116). Twenty-seven per cent of the mildly atypical, 43% of the moderately, 77% of the severely atypical adenomas and 91% of the colorectal carcinomas were distinctly aneuploid. In the aneuploid lesions p53 immunoreactivity was not observed in mildly atypical adenomas, whereas 17% of the moderately atypical, 24% of the severely atypical adenomas and 66% of the adenocarcinomas were p53 positive. None of the diploid lesions were p53 immunoreactive. These data are interpreted to indicate that genomic instability as reflected by crude aneuploidy occurs early during genesis of colorectal carcinoma and represents a high risk factor for p53-gene mutation.

Adenocarcinoma↗

PubMed1993

Proliferating cell nuclear antigen (PCNA) expression and nuclear DNA content in predicting recurrence after radiotherapy of early glottic cancer.

Proliferating cell nuclear antigen (PCNA) is a DNA replication protein maximally elevated in late G1 and S phases of the cell cycle. By using monoclonal antibodies, the expression of PCNA can be quantified and the rate of tumour cell proliferation estimated. The degree of DNA aberration in a tumour cell population reflects its genetic instability and has been implicated as a prognostic factor in an increasing number of solid tumours. The nuclear DNA content can be assessed by densitometric image cytometry DNA analysis. Both PCNA and DNA analysis can be performed on histological sections from paraffin embedded biopsies. In search of efficient and reproducible methods to identify early glottic cancers with increased risk for recurrence after radiotherapy, the PCNA expression as well as the DNA content of the diagnostic biopsies from 28 T1N0M0 glottic cancers were assessed. The group of tumours which recurred locally after radiotherapy displayed lower PCNA expression and higher DNA aberration than the group of tumours which were cured. Moreover, a combination of both parameters improved the possibility to discriminate the two groups. For T1 glottic cancer displaying high grade of genetic instability or low grade of proliferation, treatment regimes other than radiotherapy and closer follow-ups could be considered.

Adult↗

PubMed1992

Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagus. A prospective randomized multicentre study: the second Scandinavian trial in esophageal cancer.

Survival and swallowing function were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radiotherapy was given to 51 patients, while 46 patients had two courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 years in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy.

Aged↗

PubMed1992

The prognostic value of cytometric DNA analysis in early stage tongue cancer.

In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies.

Adult↗

PubMed1991

Tumor markers.

Explore the source record for details and available documents.

Biomarkers, Tumor↗

PubMed1990

Analysis of serum placental alkaline phosphatase activity in testicular cancer and cigarette smokers.

Serum PLAP/PLAP-like enzymes are elevated in testicular cancer patients and also in heavy smokers. Such elevations were measurable with anti-PLAP polyclonal and monoclonal antibodies, and an antigenic heterogeneity was demonstrated in the circulating enzymes. Thus polyclonal antibody revealed more of tumor PLAP-like antigen while a monoclonal antibody H7 detected PLAP of smokers better. PLAP of smokers and PLAP-like enzyme of cancer (seminoma) patients showed similar characteristics with respect to glycosylation pattern, charge and hydrophobicity. By these properties they were differentiated from PLAP of placenta.

Alkaline Phosphatase↗