Cell proliferation at the leading invasive front of colonic carcinomas. Preliminary observations

Dilated neoplastic glands, some with a layer of flat tumour cells and others lacking a group of consecutive lining tumour cells (i.e., glandular gaps called pores), were previously found at the leading invading tumour edge of colorectal carcinomas. Through the glandular pores, the retained intraglandular material was siphoned off directly into the juxtaposed extracellular matrix (ECM). The tumour cell fabricates, rich in proteolytic enzymes, disrupted the paratumoral anatomy of the ECM and encouraged further tumour penetration. In this work, cell proliferation in the neoplastic glands of the outermost advancing front of seven colonic carcinomas was studied with the proliferation marker Ki67. A total of 105 neoplastic glands were investigated in the seven tumours. In 33 of the 35 neoplastic glands with flat tumour cells, no Ki67 expression could be recorded in the flat cells. In the other two neoplastic glands, only occasional flat tumour cells showed Ki67 expression. The remaining (non-flat) neoplastic cells in the lateral and proximal aspects in the same 35 glands showed Ki67 expression. In 19 out of the 35 neoplastic glands with pores, the tumour cells at the tip of the pores (non-flat) showed Ki67 expression. In the remaining 16 neoplastic glands with pores, the tumour cells at the tip of the pores showed no Ki67 expression. In 15 out of the 35 neoplastic complete glands (i.e., having neither flat tumour cells nor epithelial pores) variable amounts of tumour cells lacking Ki67 expression were seen at the leading invading front. In the remaining 20 complete glands, all tumour cells showed Ki67 expression at the leading invading front. These preliminary results showed, for the first time, that human colonic flat neoplastic cells arrest their proliferation at the invading tumour front. The possibility that these Ki67-negative tumour cells were arrested in G1-phase was entertained. It is not inconceivable that this unexpected paradoxical biological behaviour of flat tumour cells might be connected with the formation of glandular pores at the level of advancing invasion in colonic carcinomas.