'Anti-metastatic' nm23 gene product expression in keratoacanthoma and squamous cell carcinoma.
An inverse correlation has been demonstrated between nm23 gene expression and metastasis. The gene is located on chromosome 17q (q1.1-q2.1), a region distinct from tumour suppressor gene p53. We have previously reported expression of mutant products of p53 gene to be significantly associated with worsening degrees of differentiation in squamous cell carcinoma. nm23 gene product, which shows complete identity to human erythrocyte nucleoside diphosphate kinase, was used to raise an affinity-purified polyclonal antibody Ab-11 which is applicable to formalin-fixed and paraffin-embedded tissues. Keratoacanthomas and squamous cell carcinomas of the epidermis form a fascinating human tumour model in which to test the hypothesis that the nm23 gene confers 'anti-metastatic' properties, since the former never metastasise while the latter have this potential. Two observers rated immunohistochemistry for the nm23 gene product as the proportion of tumour positive from grades 1-4 (corresponding to 25, 50, 75 and 100% of tumour cells stained). Nineteen typical keratoacanthomas, 20 well, 21 moderately and 8 poorly differentiated epidermal squamous cell carcinomas were studied. The Jonckheere-Terpstra test statistic of association between staining grade and lesion type was 762.5, p = 0.189 (2 tails), p = 0.0945 (1 tail). There was no statistically significant trend in tumour staining from keratoacanthoma through decreasing grades of differentiation of squamous cell carcinoma. nm23 product expression does not appear to correlate with differentiation, itself an indicator of metastatic potential, in this system of human squamous cell neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
Stephenson
T J
TJ
Department of Pathology, University of Sheffield Medical School, UK.
Royds
J A
JA
Bleehen
S S
SS
Silcocks
P B
PB
Rees
R C
RC
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007636:Keratoacanthoma / Q000235:genetics* / Q000473:pathology; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis*
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins