Pepsinogens I and II in carcinoma of the stomach: an immunohistochemical study.

Pepsinogen I is normally produced by the chief and mucus neck cells of the fundic glands, while pepsinogen II is produced by these cells and by the cardiac and pyloric glands. In this study we used antisera specific for human pepsinogen I and II to identify these antigens in tumor tissue from 64 patients with gastric carcinoma. In addition, we examined the relationship between tumor positivity and preoperative serum levels of pepsinogens I and II. Histologically, 44 of the 64 cancers were of the intestinal type (gland forming) and 20 were of the diffuse type. Of the intestinal type tumors, 16 (36.4%) contained pepsinogen II, while only 2 (4.5%) contained pepsinogen I; one tumor contained both antigens. Pepsinogen II-positive cells were found in undifferentiated and in moderately well-differentiated intestinal type tumors, but not in intestinalized gastric mucosa or in tumors arising from intestinalized glands. This suggests that tumors containing PG II arise from antral gland mucosa even when most of the antrum has undergone intestinal metaplasia. None of the 20 diffuse tumors was positive for pepsinogen I and only 3 (15%) were positive for pepsinogen II. Serum pepsinogen II levels were available in 35 patients. The mean (+/- SE) level in 6 patients with pepsinogen II-positive tumors was 29.1 +/- 3.3 micrograms/l. This was higher than the mean level of 16.0 +/- 2.1 micrograms/l in the 29 patients with pepsinogen II-negative tumors (p = 0.011). Serum pepsinogen I was elevated to 152 micrograms/l in 1 of 2 patients with a pepsinogen I-positive tumor. The results suggest that tumor pepsinogen I and II enter the circulation and contribute to their respective serum levels.