Evaluation of Apoptosis as a Factor Affecting the Growth of Non-Polypoid Colorectal Adenomas

Abstract

Some colorectal adenomas show non-polypoid features endoscopically, e.g. nodule-aggregation or lateral spreading. To understand the developmental mechanism of non-polypoid adenomas better, we evaluated apoptosis indices in the upper and lower parts of 26 colorectal adenomas of non-polypoid appearance using TUNEL or single-stranded DNA (ssDNA) immunohistochemical staining. Regression analysis showed an extremely strong positive correlation between the apoptosis index (AI) values generated using each method. The AI of the lower section of lesion (4.54 +/- 1.86) was significantly higher than that of the upper part (1.21 +/- 1.47). In conclusion, ssDNA immunostaining is as useful as the TUNEL method in the evaluation of apoptosis in colorectal adenomas. It seems that vertical growth in non-polypoid adenomas is inhibited by apoptosis allowing horizontal growth to dominate and resulting in the characteristic, laterally spreading morphology.

Clinicopathological Characteristics in Large, Non-Polypoid Colorectal Adenomas with Granule-Aggregating Appearance

“…As in our previous report, 6 GAT is defined as follows: (i) Colorectal laterally spreading tumour with a granule-aggregating appearance composed of granules or elevations of small, flat lesions, projecting above the surrounding mucosa, macroscopically measuring 1 -2 mm; (ii) Maximal tumour diameter more than 10 mm; (iii) No apparent ulcer formation on the tumour surface; (iv) Tissue classified as 'tubular adenoma' and 'tubulovillous adenoma' with a villous component accounting for 0 -24% and 25 -74% of the tumour, respectively. All specimens were fixed with 10% buffered formalin, and routinely processed and embedded in paraffin for histological examinations.…”

“…We previously investigated the extent of apoptotic cell loss in large, H Yamada, H Hasegawa, H Iino et al Large, non-polypoid colorectal adenomas non-polypoid adenomas and found dominant apoptosis in lower parts of the tumour, which is thought to be a characteristic related to the unique mode of development of such tumours. 6 In the present study, we reviewed and morphometrically analysed 26 previously investigated large, non-polypoid adenomas in order to clarify their clinicopathological characteristics. 6…”

“…6 In the present study, we reviewed and morphometrically analysed 26 previously investigated large, non-polypoid adenomas in order to clarify their clinicopathological characteristics. 6 …”

Low Frequency of bcl-2 Expression in Large Non-Polypoid Colonic Neoplasms

“…Positively staining tumour cells with the morphological characteristics of apoptosis were identified using standard criteria, including chromatin condensation, nuclear disintegration and formation of crescent-shaped caps of condensed chromatin at the nuclear periphery. 12 Positively staining cells without signs of apoptosis or with cell bodies located in the stroma and lumens were excluded. Each lesion was divided into two parts, upper and lower half of the tumour, in which apoptotic cells were counted in each 1000 cell portion.…”

Gene expression profiling of laterally spreading tumors

“…Yamada et al in non-polypoid colorectal adenomas (non-PAs), significant differences between apoptosis in the upper and lower portions of lesions suggests that vertical growth in non-PAs seems to be inhibited by apoptosis. Consequently, horizontal growth comes to dominate over vertical growth, resulting in the laterally spreading morphology of non-PAs [ 31 ]. Based on these reports, we suggest that anti-apoptotic gene Bcl-2 which have differential gene expression between LSTs-adenoma and Ip-adenoma may play an important role in the morphogenesis of LSTs by being responsible for apoptotic expression.…”