Diagnostic Implication of Measurement of Serum Type I Procollagen Carboxyterminal Peptide in the Patients with Scirrhous Carcinoma of the Stomach

Scirrhous carcinoma of the stomach is characterized by the extensive deposition of collagen with sparse tumor cell infiltration in the desmoplastic stroma, and clinically by the worst prognosis of any type of gastric carcinoma. Although many biochemical parameters have been used in the diagnostic method, the x-ray examination and endoscopic examination are still the most reliable diagnostic methods. In the present study, we evaluated the use of radioimmunoassay （RIA） for type I procollagen carboxyterminal peptide （type I C-peptide） which is liberated from type I procollagen during its conversion to collagen, in serodiagnosis of scirrhous carcinoma of the stomach. The results obtained are as follows; 1） By CM-cellulose column chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis （SDS-PAGE） and amino acid analysis, the interstitial fibrous tissue of a scirrhous carcinoma was revealed to be composed mainly of type I and type III collagens. 2） On the basis of the above observation, an RIA for type I C-peptide purified from a culture medium of human fibroblast （IMR-90） was established and applied for the measurement of serum type I C-peptides levels. The mean serum level of type I C-peptide in 39 normal subjects was found to be 41.7±19.7 ng/ml. In all the benign digestive diseases which included chronic gastritis, gastric ulcer, gastric polyp and chronic pancreatitis, serum type I C-peptide levels stayed within the normal range. The mean serum levels and the positive ratio of type I C-peptide in 11 patients with scirrhous carcinoma of the stomach were 91.2±41.9 ng/ml and 54.5 percent, respectively, at stage II and III. In 10 patients with other types of gastric? carcinoma, the mean type I C-peptide levels were well within the normal range. 3） At stage IV of the scirrhous carcinoma, serum type I C-peptide level appeared to increase, although statistically not significant, reflecting the extent of tumor burden. In non-scirrhous gastric carcinoma, serum type I C-peptide levels also increased at stage IV, particularly in the cases with liver metastasis, suggesting that the non-scirrhous carcinoma are producing the collagen, although to a lesser degree as compared to scirrhous carcinoma, and in the liver where the metastatic foci are surrounded by an abundant blood stream, the peptides are readily released into circulation. 4） Similar elevations of serum type I C-peptide were observed in the patients with metastasis to the liver from carcinoma of the colon, esophagus, pancreas and gallbladder indicating that the synthesis of collagen also occurs in these carcinomas. 5） Serum type I C-peptide levels corresponded to the clinical course of 5 patients with scirrhous carcinoma of the stomach who underwent either operation or chemotherapy. Collectively, the measurement of serum type I C-peptide concentrations will provide a new means for diagnosis and monitoring the scirrhous carcinoma of the stomach, especially for those patients with no liver metastasis.