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2 Table 1 Flow chart for localizations of tumor markers and pancreatic exocrine enzymes by immunoperoxidase methods Table 2 Sensitivities of tumor markers and pancreatic exocrine enzymes for the diagnosis of pancreastic cancer and specificities of these markers studied in cases of chronic pancreatitis ć UAm/Cr: Am/Cr ratio in urine method normal range
3 Table 3 Correlation between various serum markers and urinary amylase in cases of pancreatic cancer Each value means correlation coefficient * p<0.05 Table 4 Distribution of various tumor markers and pancreatic exocrine enzymes in the tissues of normal part of pancreas studied in formalin-fixed, paraffin sections (19 cases) Table 5 Distribution of various tumor markers and pancreatic exocrine enzymes in the necrotic tissue (11 cases) and intralumi nal deposits of pancreas tumors (22 cases) studied in formalin-fixed, paraffin sec tions (): Case number of exceptional cases (Table 6) +: positive+: negative (): Case number of exceptional cases (Table 6) +: positive-: negative
4 6 Expression of tumor markers and pancreatic exocrine enzymes in the tissues of pancreatic tumors Table and their levels in serum and urine No. 4 `26 are cases of pancreatic cancer
5 œ a. CEA and TPA d. TPA and CA 19-9 b. CEA and CA 19-9 e. TPA and POA c. CEA and POA f. CA 19-9 and POA : pancreatic cancer : other tumors Fig. 1 Relationship between the expression of tumor markers in the tissues of pancreatic tumors
6 a. Localization of CEA on the luminal border, cytoplasma, marginal region of cancer cells and intra luminal deposits. The intensity of the staining is different from one cancer cell to another. 3.3 ~ 4 Left lower corner is the high power view. 3.3 ~20 b. Localization of TPA on the luminal border, cytoplasma and marginal region of cancer cells. No stain ing of the intraluminal deposits. Marginal region of the cell is more strongly stained than that of CEA. Acinar epithelial cells are also stained. 3.3 ~4 Left lower corner is the high power view. 3.3 ~20 Fig. 2 Well differentiated adenocarcinoma of the pancreas (Case No. 16 Table 6)
7 a. CA19-9-staining of the same specimen of fig. 2. Localization of CA19-9 resembles that of CEA. 3.3 ~ 4 Left lower corner is the high power view. 3.3 ~20 b. Modelately differentiated adenocarcinoma of the pancreas (Case No. 18 Table 6) Elastase 1-staining is strong on cytoplasma of cancer cells. 3.3 ~4 Left lower corner is the high power view. 3.3 ~20 Fig. 3
8 a. POA-staining showing granular pattern in cytoplasma of cancer cells and exceptional staining of intraluminal deposits. 3.3 ~4 Left lower corner is the high power view. 3.3 ~20 b. Localization of Ferritin. No staining on cancer cells but on surronding stroma. 3.3 ~4 Left lower corner is high power view. 3.3 ~20 Fig. 4 Modelately differentiated adenocarcinoma of the pancreas (Case No. 9 Table 6)
9 a. CEA c. CA 19-9 b. TPA d. POA Undiff. Undifferentiated Poor. diff. Poorly differentiated Moder. diff. Moderately differentiated Fig. 5 Relationship between the expression of tumor markers and tumor-cell differentiation in specimens of pancreatic cancer
10 œ a. CEA _??_ normal range C. CA 19-9 _??_ normal range Expression of CEA in the tissues Expression of CA 19-9 in the tissues b. TPA _??_ normal range : measured with RIA (_??_ normal range) : measured with EIA (_??_ normal range) d. POA Expression of TPA in the tissues Expression the tissues of POA in Fig. 6 Comparison of the expression of CEA, TPA, CA19-9 and POA in the tumor specimens with their levels in serum
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14 5. Hirai H: A collaborative clinical study of cacinoembryonic antigen in Japan. Cancer Res (1977) 37, Del Villano B C, Brennan S, Brock P, Bucher C, Liu V, McClure M, Rake B, Space S, Westric B, Shoemaker H and Zurawski VRJ: Radioimmunometric assay for a monoclonal antibody-defined tumor marker, CA19-9. Clin Chem (1983) 29, Gelder F B, Reese C J, Moosa A R, Hall T and Hunter R: Purification, partial characterization, and clinical evaluation of a pancreatic oncofetal antigen. Cancer Res (1978) 38,
15 14. Tsutsumi Y, Nagura H, Watanabe K: Immunohistochemical observations of carcinoembryonic antigen (CEA) and CEA-related substances in normal and neoplastic pancreas - Pitfalls and Caveats in CEA immunohistochemistry-. Am J Clin Pathol (1982) 82, Nathrath WBJ, Heidenkummer P Bjorklund V and Bjorklund B: Distribution of tissue polypeptide antigen (TPA) in normal human tissues: Immunohistochemical study on unfixed, methanol-, ethanol-, and formalin-fixed tissues. J Histochem Cytochem (1985) 33, Atkinson BE Ernst CS, Herlyn M, Steplewski Z, Sears HF and Koprowski H: Gastrointestinal cancer-associated antigen in immunoperoxidase assay. Cancer Res (1982) 42, Hobbs JR. Knapp ML and Branfoot AC: Pancreatic oncofetal antigen (POA): its frequency and localization in humans. Oncodev Biol Med (1980) 1, Denk H, Tappeiner G, Eckerstorfer R and Holzner JH: Carcinoembryonic antigen (CEA) in gas trointestinal and extragastrointestinal tumors and its relationship to tumor-cell differentiation. Int J Cancer (1972) 10, Goldenberg DM, Sharkey RM and Primus FJ: Immunocytochemical detection of carcinoembryonic antigen in conventional histopathology specimens. Cancer (1978) 42, Zamcheck N and Martin EW: Factors controlling the circulating CEA levels in pancreatic can cer: Some clinical correlations. Cancer (1981) 47,
16 Immunohistochemical study of tumor markers (CEA, TPA, CA19-9, POA and Ferritin) and pancreatic exocrine enzymes (Amylase and Elastase 1) in pancreatic tumors Isao WAKIYA First Department of Internal Medicine, Okayama University Medical School The distribution of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), pancreatic oncofetal antigen (POA), Ferritin, Amylase and Elastase 1 was studied immunohistochemically using an immunoperoxidase method in 26 conven tional histopathologic sections of pancreatic tumor. CEA and CA19-9 were regarded as markers secreted into the glandular lumina from cancer cells, but TPA and POA were not. The expression of these markers was different from one case to another and had no fixed pattern in cases of pancreatic cancer. The degree of CEA staining correlated positively with that of TPA. CEA, TPA and CA19-9 were demonstrated on the luminal border, cytoplasma and marginal region of cancer cells in various degrees, but POA was only found in the cytoplasma of cancer cells. CEA, TPA and CA19-9 tended to be stained more strongly as the pancreatic cancer was more highly differentiated. The specimens were more frequently stained with CEA and TPA than with CA19-9. In two cases, CA19-9 was not expressed in tumor specimens, although serum levels of this marker were abnormally elevated. In these cases CA19-9 in normal epithelium of the pancreatic duct and choledochus may have leaked into the blood stream. The same pro cess was considered in one case each of TPA and POA expression. TPA, Ferritin and Elastase 1 were expressed in two cases of islet cell tumor, while none of them was expressed in one case of apudoma. Elastase 1 was stained intensively on tumor cells in one case of pancreatic cancer and one case of islet cell tumor.
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