Morphologically distinct patterns of apoptosis correlate with size and high-grade dysplasia in colonic adenomas

Aims: To examine the relationship of morphological patterns of apoptosis in colonic adenomas to standard pathological variables. Methods and results: Apoptosis patterns were evaluated in 184 consecutive colonic adenomas and 14 adenocarcinomas, using haematoxylin and eosin sections. Apoptosis identification was selectively validated by electron microscopy. There were three patterns of apoptosis: (i) confluent basal apoptosis; (ii) crypt lumen apoptosis, both assessed semiquantitatively; and (iii) scattered apoptosis (not quantified). Adenoma site, size, type, mitoses, and grade of dysplasia were also assessed. MIB-1 immunostaining was performed in 20 cases. In 142 adenomas (77%) confluent basal apoptosis (n = 124) and/or crypt lumen apoptosis (n = 69) were identified; 42 (23%) had scattered apoptosis only. Significant correlations were: (i) extensive confluent basal apoptosis with small adenomas ≤5 mm (P < 0.0001); (ii) crypt lumen apoptosis with large adenomas >5 mm (P < 0.0001) and (iii) with high-grade dysplasia (P < 0.0003); and (iv) coexistence of both patterns (n = 51) with large adenomas >5 mm (P < 0.0001). Neither apoptosis pattern correlated with other variables. Adenocarcinomas had minimal confluent basal apoptosis (5/14), conspicuous crypt lumen apoptosis (14/14), intraglandular coagulative necrosis, and scattered apoptotic tumour cells. Conclusions: Confluent basal apoptosis is maximal early in colonic tumorigenesis. The 'switch' to a predominant crypt lumen apoptosis pattern suggests that a different apoptosis induction mechanism might be associated with the transition to adenocarcinoma.