P16 CDKN2 ALTERATIONS AND PRB EXPRESSION IN ESOPHAGEAL SQUAMOUS CARCINOMA/

Background-Upregulation of the cell cycle associated genes, p16/CDKN2 and the retinoblastoma susceptibility gene (Rb), is commonly seen duri ng the proliferation of normal cells. An inverse relation between the expression of p16/CDKN2 and Rb has been noted in many tumours, but has not yet been determined in oesophageal squamous carcinoma. Aims-To in vestigate p16/CDKN2 genetic alterations and both the p16/CDKN2 and the Rb protein (pRb) immunophenotypes in oesophageal squamous carcinoma. Methods-Twenty primary oesophageal squamous carcinomas were examined f or mutations in p16/CDKN2 by the polymerase chain reaction, single str anded conformational polymorphism, and DNA sequencing. Synthesis of p1 6/CDKN2 and pRb proteins was determined by immunohistochemistry in 19 specimens of formalin fixed, paraffin wax embedded tissues. Results-Mu tations of p16/CDKN2 were not detected in exons 1 and 2. In only one c ase, G to C and C to T base changes were detected in a non-coding regi on of exon 3. Expression of p16/CDKN2 and Rb was observed in both norm al and neoplastic areas of tissue sections, indicating neither consist ent homozygous deletion nor consistent hypermethylation of the genes i n tumours. Fourteen tumours showed an inverse expression of p16/CDKN2 and Rb. An increased percentage of cells that immunostained positively for p16/CDKN2 but not for pRb was observed in eight tumours, five of which had no detectable pRb, suggesting defective Rb expression in the se oesophageal squamous carcinomas. Conclusions-These results indicate that p16/CDKN2 mutations occur infrequently in oesophageal squamous c arcinoma. The alteration of the Rb gene is suggested as an important s tep in the development of these tumours.