Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx.

Squamous epithelial cancer in situ (CIS) of the upper aerodigestive tract is a histopathologically well-defined condition. 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 immunohistochemical staining with a polyclonal antibody against recombinant gamma 2 chain of laminin-5 in 33 laryngeal CIS lesions. All six CIS lesions which progressed to invasive cancer, within a follow-up time of 5 years, were laminin-5 positive (100%), whereas only 10 out of 27 lesions which did not progress were positive (37%) (p < 0.01). Our data showed that a positive laminin-5 laryngeal CIS lesion indicates a high risk for progression to invasive cancer.

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.

TP53 mutations do not correlate with locoregional recurrence in stage I tongue carcinomas.

BACKGROUND: The abrogation of the TP53 gene is considered to play a central role in the development of human cancers. Exons 5-8 harbor mutations most frequently, mainly of the missense type, resulting in accumulation of the p53 protein. The importance of these alterations as prognostic factors, are issues of controversy. MATERIAL AND METHODS: Thirty-four patients suffering from stage I tongue carcinoma had been treated with a local surgical excision of the tumor. Seventeen patients had developed a local recurrence in the tongue or cervical (regional) metastases while 17 patients, matched for age and gender to the former group, had no recurring disease within follow-up. Protein p53 was detected through immunohistochemical (IHC) analysis using antibody CM1. Exons 5-8 of the TP53 gene were amplified through the Polymerase Chain Reaction (PCR). The presence of mutations analyzed by CDGE (Constant Denaturant Gel Electrophoresis) and detected mutations were subjected to sequencing. RESULTS: 20 out of 34 tumors (59%) showed mutated TP53, 18 tumors were IHC p53 positive, but the correlation between CDGE and IHC was only 56%. Sequencing of the gene was possible in 8 cases. CONCLUSIONS: Neither the presence of mutations nor immunostaining had any impact on the risk of recurrence expressed as life-table analysis of time to recurrence.

Preneoplastic oral lesions: the clinical value of image cytometry DNA analysis, p53 and p21/WAF1 expression.

BACKGROUND: Various mucosal lesions are frequently encountered in the oral cavity. Neither macroscopic nor microscopic evaluation of these lesions gives any reliable information concerning the risk of cancer development. MATERIAL AND METHODS: From 21 patients, 29 mucosal lesions were found to precede development of invasive squamous cell carcinoma or carcinoma in situ at the same location. The lesions were matched to 29 control lesions, with the same grade of dysplasia and from exactly the same locations but without subsequent cancer during a mean follow up of 112 months (46-194). The specimens were evaluated using Image Cytometry DNA analysis and immunohistochemical analysis of p53 and p21/WAF1 expression. RESULTS: Lesions prior to carcinomatous development displayed a higher degree of DNA aberration as compared with the control lesions. p53 and p21/WAF1 evaluation did not reveal any differences between cases and controls. CONCLUSION: Image Cytometry DNA analysis is an useful adjunct to histopathological evaluation of oral mucosal lesions for prediction of risk of malignant transformation.

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.

Nuclear DNA content and p53 immunostaining in metachronous preneoplastic lesions and subsequent carcinomas of the oral cavity.

BACKGROUND: Clinical evaluation of preneoplastic lesions of the oral cavity is difficult. Histopathologic grading of dysplasias shows large variability and does not give reliable information concerning the risk for progression to cancer. METHODS: DNA image cytometry and p53 immunostaining were performed to describe the pattern of DNA aberration and p53 overexpression in confined preneoplastic lesions and in the subsequent carcinomas developing at the same site in 20 patients. RESULTS: Hyperplastic and/or inflammatory lesions showed a diploid DNA pattern in 81% of the cases and 23% were p53-positive. Dysplastic preneoplastic lesions showed a nondiploid/ aneuploid DNA pattern in 73% and 64% were p53-positive. The subsequent invasive carcinomas were nondiploid/aneuploid in 86% and p53-positive in 69% of cases. CONCLUSIONS: Analysis of nuclear DNA content and p53 immunostaining appears to be useful as an adjunct to histopathology in the evaluation of true precancerous lesions.

Borreliosis as a cause of peripheral facial palsy: a multi-center study.

Borreliosis is known to be a common cause of peripheral facial palsy in Stockholm and its vicinity. The aim of the present study was to investigate the frequency and characteristics of borreliosis among patients with peripheral facial palsy in different parts of Sweden. All serological tests were performed in one laboratory. Ten Swedish Ear Nose and Throat clinics participated in a prospective 1-year study of patients seeking medical attention for acute peripheral facial palsy. Twenty-eight (6%) out of totally 446 patients fulfilled the criteria for the diagnosis of borreliosis. The frequency varied between 1 and 16% and was highest along the southeast coast of Sweden whereas no case was reported from the northern part of the country. Borreliosis was more common among children with facial palsy than among adults. The infection occurred during all seasons although it appears to be less frequent during the spring months. Only a minority of the borrelial patients had a history of a preceding tick bite or erythema migrans. The fairly low overall frequency of this secondary stage of borreliosis in the study may be a result of better knowledge of the disease and earlier treatment of its early manifestations. In Sweden's endemic areas borreliosis is a common cause of peripheral facial palsy, and therefore all patients with facial palsy in these regions should be examined for borrelial infection.

Nuclear-DNA content and p53 immunostaining in oral squamous-cell carcinoma - an analysis of a consecutive 10-year material.

In a retrospective analysis of 91 consecutive oral carcinomas we reviewed all patient records and weighed clinicopathological parameters against the results of image DNA cytometry and p53 immunhistochemical staining of the initial diagnostic biopsies. Eighty-seven percent of the biopsies were either aneuploid or nondiploid and there was a significant correlation between poorly differentiated tumours and aneuploidy. Sixty-nine percent of the tumours were p53 positive. DNA aberration or p53 positivity had no significant impact on prediction of survival or susceptibility to radiotherapy. In a multivariate analysis, T category had the greatest predictive value concerning survival. There was no correlation between p53 positivity and smoking.