Forty four cases of human gastric carcinoma were classified as either diffuse or intestinal in type. Serial sections of the paraffin-embedded tumours were stained with either monoclonal antibodies raised against transforming growth factor (TGF-alpha) or proliferating cell nuclear antigen (PCNA) or an affinity purified polyclonal antibody raised against the intracellular domain of the epidermal growth factor receptor (EGFR). Significantly higher levels of staining were found in the intestinal-type carcinomas with all three antibodies. When the extent of staining was arbitrarily divided into low (up to one third of cells stained), medium (one third to two thirds) or a high number of cells stained (two thirds to all of the cells), a much higher proportion (44%) of intestinal type tumours coexpressed TGF-alpha and EGFR to a medium or high level compared to the diffuse group (23%). In the intestinal-type tumours, though not in the diffuse-type tumours, this subgroup of tumours was associated with higher levels of PCNA staining. The relative lack of TGF-alpha or its receptor may be a significant factor in the histogenesis of diffuse gastric carcinoma, and in intestinal-type tumours the coexpression of TGF-alpha and EGFR may be part of an autocrine loop which stimulates the cells to divide.

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