Lack of cyclin D1 overexpression in gastric carcinogenesis

Aims: Cyclin D1 overexpression was examined in early gastric carcinomas and precursor lesions with the following aims; (1) to assess the chronology of cyclin D1 overexpression in various stages of gastric carcinogenesis, (2) to correlate cyclin D1 overexpression with the Lauren type, the grade of differentiation and the type of growth pattern of the tumours and (3) to correlate cyclin D1 overexpression with clinical parameters, in particular lymph node metastasis and overall prognosis. Methods and results: Forty-five paraffin-embedded gastrectomy specimens from early carcinomas were examined for the presence of various precursor lesions. The Lauren type, the grade of differentiation and the type of growth pattern were reassessed for all early carcinomas. Cyclin D1 overexpression was examined using the monoclonal antibody DCS-6. Cyclin D1 overexpression was absent from all precursor lesions. Ten early carcinomas (22%) were cyclin D1 positive without significant differences when stratified according to Lauren type, grade of differentiation, type of growth pattern or lymph node status. Univariate analysis failed to show a significant difference in 5-year surival rate between cyclin D1 positive and negative early carcinomas (90% vs. 94%). Conclusions: Cyclin D1 protein overexpression does not play a role in the progression from normal to neoplastic gastric mucosa and does not discriminate between intestinal and diffuse type early gastric carcinomas of Caucasian origin. Moreover, mechanisms other than cyclin D1 protein overexpression underlie the reported difference in biological behaviour of early gastric carcinomas with different types of growth pattern. Finally, although it appears that cyclin D1 does not have prognostic significance, studies on larger numbers, including advanced carcinomas, are warranted.