P. B. Silcocks

Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma

The tumour suppressor gene p53, located on the short arm of chromosome 17, encodes for a nuclear protein which regulates cell proliferation by inhibiting cells entering S‐phase. p53 mutations are alleged to be the commonest genetic abnormality in human cancer. We studied mutant p53 oncoprotein expression, using PAb1801 monoclonal antibody immunohistochemistry, in 25 ‘ideal’ keratoacanthomas and 26 well‐, 19 moderately and 18 poorly differentiated squamous cell carcinomas of the skin. While there was a highly significant trend in the proportion of p53 oncoprotein‐positive lesions from keratoacanthomas to poorly differentiated squamous cell carcinomas (χ2= 17·13, df=l, exact P=0·00003), p53 expression was inadequate for distinguishing keratoacanthoma from well‐differentiated squamous cell carcinoma (χ2= 2·55, df = 1, exact P = 0·18; corresponding to a sensitivity of 0·84 and a specificity of only 0·36).

Clinicians and the coronial system: ability of clinicians to recognise reportable deaths.

OBJECTIVE--To assess the ability of clinicians to recognise deaths which require referral to the coroner. DESIGN--Postal questionnaire consisting of 16 fictitious case histories, 14 of which contained a clear indication for referral to the coroner. SETTING--Large teaching hospital. Coroners office. SUBJECTS--200 clinicians from general medical and surgical firms and senior staff of the local coroners office (two coroners officers and the two deputy coroners). MAIN OUTCOME MEASURES--Number of correct assessments on questionnaire. RESULTS--The mean recognition score for the clinicians was 9.11 (range 3-14) with no difference between the clinical grades. All of the coroners senior staff recorded maximum recognition scores of 16. CONCLUSIONS--The study highlights several features of the coronial system which are poorly understood by clinicians and provides the basis for an initiative to improve the medicolegal education of all clinicians.

DIAGNOSTIC ASSOCIATIONS OF P53 IMMUNOSTAINING IN FINE NEEDLE ASPIRATION CYTOLOGY OF THE BREAST

Duplicate cytospin preparations were made from 46 symptomatic breast fine needle aspirates. One of each pair was assigned to benign or malignant categories by one experienced observer as part of the ‘triple approach’patient assessment. the other was immunostained with DO7, a monoclonal antibody to recombinant p53 protein, and rated by another observer as positive or negative for nuclear staining, unaware of the cytodiagnosis. Positive controls included carcinomas known to have mutant p53, while negative controls were of the reagent substitution type. of the 26 aspirates with a benign cytodiagnosis (verified by the triple approach), 23 were p53 protein‐negative and three positive. of the 20 with a malignant cytodiagnosis (histologically confirmed), six were p53 protein‐negative and 14 positive (exact P<0.0001). As a diagnostic test this would give 70% sensitivity and 88% specificity.