The presence of carcinoembryonic antigen (CEA) was assessed in cancer tissues of 53 patients with esophageal carcinoma. Positive rates of CEA staining in tissues were 81.1%. Well differentiated carcinomas tended to be well stained. The survival time in positive tissue CEA patients was longer than that in negative one. The measurement of a presence of tissue CEA is of help to judge the prognosis

Ayabe Hiroyoshi

Ide Seiichiro

Kawahara Katsunobu

Nakamura Akihiro

Sasaki Nobufumi

Shingu Hiroshi

Tagawa Yutaka

Takahashi Takao

Tomita Masao

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Acta Med. Nagasaki 38:158 - 160CEA in Esophageal Cancer TissuesMasao Tomita, Hiroyoshi Ayabe, Katsunobu Kawahara, Yutaka Tagawa, Akihiro Nakamura, Nobufumi Sasaki, Takao Takahashi, Seiichiro Ide and Hiroshi ShinguThe First Department of Surgery, Nagasaki University School of MedicineThe presence of carcinoembryonic antigen (CEA) was assessed in cancer tissues of 53 patients with esophageal carcinoma.  Positive rates of CEA staining in tissues were 81.1%. Well differentiated carcinomas tended to be well stained. The survival time in positive tissue CEA patients was longer than that in negative one. The measurement of a presence of tissue CEA is of help to judge the prognosis.Table 1. Number of cases on the serum CEA level and CEA stain of esophageal cancerS-CEA No. of cases (%) CEA stain No. of cases (%) negative 44 (91.7) negative 10 (18.9) positive 4 ( 8.3) positive 43 (81.1)  total 48(100) total 53(100)Introduction It has been well known that carcinoembryonic antigen (CEA) is one of the tumor-markers, in particular, it is sensitive to well differentiated adenocarcinoma. Further-more, changes in CEA is of clinical value in knowing occurrence and appearance of recurrence in the follow-up study.  The CEA measurement in patients with carcinoma of the esophagus is of great benefit in the diagnosis of carcinoma of the breast, the lung and the stomach as well as the colon.   In this study, the serum CEA levels were compared with the intensity of tissue CEA staining of esophageal carci-nomas to elucidate CEA transition from the cancer-bearing tissues to the serum in terms of pathohistological factors.levels were not correlated with the tissue CEA staining which implied CEA production in carcinoma cells. Positive tissue CEA staining was rarely seen in undifferentiated carcinoma.  Table 2 showed a relationship between histologic find-ings and positive rates of tissue CEA staining. The positive rate of tissue CEA staining shows higher tendency in well differentiated adenocarcinoma rather than poorly one. According to growth patterns of the tumors, the rates of tissue did not vary with growth patterns.Table 2. Correation between CEA stain and histologic classification-differentiation and growth patternMaterial and Method Surgical specimens obtained from 53 patients with carci-noma of the esophagus were subjected in this study. Fifty-three patients comprised 52 of squamous cell carcinoma and one of adenocarcinoma according to histologic types.  The sex distribution was 42 men and 11 women. The patients' ages ranged from 44 to 80 with a mean age of 63.7 years old.  The relationship in positive rates between tissue and serum CEA was shown in Table 1. There was no close correlation. CEA production, which was thought to be represented in positive tissue CEA staining, was not neces-sarily reflected in the serum CEA levels. The serum CEA                                 no. of cases                      well. mod. poor.   CEA stain - 0 6 1  CEA stain + 14 20 3 N. S.                                  no. of cases                       expan. mod. inv. mark. inv.   CEA stain - 1 5 1  CEA stain + 7 18 12 N. S. Each a growth pattern showed almost the same rate as tissue CEA staining.  In view of the gross appearance, a high tissue CEA staining rate was seen in the superficial type and moder-ately clear margin as shown in Table 3. However, the positive rates of tissue. CEA staining were not affected by gross appearances or histologic types.Table 3. Correation between CEA stain and gross classification-gross types and margin                                 no. of cases                       prot. super. ulcer.   CEA stain - 4 0 6  CEA stain + 8 5 30 N. S.                                  no. of cases                    well. mod. ill.   CEA stain - 7 2 1  CEA stain + 20 19 4 N. S. There was statistically significant difference (p < 0.05) in positive tissue CEA rates between with and without vascular invasion in spite of no significant difference between with and without lymphatic vessel invasion.  A comparative study was made between the intensity of tissue CEA staining and the serum CEA levels.  Fig. I shows postoperative changes in serum CEA levels in accordance with the intensity of tissue CEA staining. As for the depth of cancer infiltration and nodal involve-ment as shown in Table 4, tissue CEA staining rates were not well correlated with the depth of cancer invasion and node metastasis. It is indicated that the tissue CEA produc-tion was actively achieved even in early cancers such as ao and no as well as advanced one such as a3 and n4.Table 4. Correation between CEA stain and histologic invasion to the adventitia, degree of lymph node metastasis                                 no. of cases                   aO al a2 a3   CEA stain - 1 3 2 2  CEA stain + 13 6 11 8 N. S.                                  no. of cases                 nO nl n2 n3 n4   CEA stain - 2 0 0 1 2  CEA stain + 11 3 10 5 8 N. S.Fig. 1. Correation between CEA stain and serum CEA level The more tissue CEA staining was intensive, the less a decrease in postoperative serum CEA levels was seen. Even in those who showed a weak tissue CEA staining, postoperative changes in serum CEA levels varied with wide variety.  The survival times were compared between those with and without tissue CEA staining.  The survival curve showed a better result in those with positive tissue CEA staining than negative one as indicated in Fig. 2. It is obvious that tissue CEA staining is an Concerning a histologic finding of vascular invasion, carcinomas without vascular invasion were more likely to be stained by CEA antigen when compared with carcinoma with vascular invasion as shown in Table 5.Table 5. Correation between CEA stain and lymphatic invasion, blood vessel invasion                                 no. of cases                  ly (-) ly (+)   CEA stain - 1 7   CEA stain + 14 22 N. S.                                  no. of cases                    v (-) v (+)   CEA stain - 1 7  CEA stain + 20 16 P < 0.05 Fig. 2. Survival rates according to tissue CEA stainindependent indicator for the prognosis of patients with carcinomas of the esophagus.Discussion It has been well known that CEA is a representative tumor marker with progression and extension of carcinomas on the basis of the fact that gene expression of growing tumors moves backward to the embryonic period.'-S'  Recent studies clarified that CEA is producing even in the normal epithelium and CEA is no longer a specific tumor marker.  Positive rates of serum CEA in carcinoma of the esoph-agus ranges from 23 to 46 percent.'' However, it is very rare that the serum CEA levels are high as seen in carci-noma of the colon.   It is documented that the serum CEA measurement is not useful as a diagnostic tool of squamous cell carcinoma. However, observation of changes in serum CEA levels is necessary for judging the therapeutic effect in the follow-up study. It is of great value to monitor the therapeutic effect in the course of the disease and predict recurrence, and also a high serum CEA level after surgery means poor surgical radicality.   Several tumor markers have been detected and used for the diagnosis of squamous cell carcinomas. However, the early diagnosis is limited by using tumor markers.  Difficulty in early diagnosis by using tumor markers is based on the fact that the serum CEA levels are low in spite of high tissue CEA staining rates (81.1%) in this study. Well differentiated carcinomas were forced to be morefrequently stained with CEA antigen. And also it is con-cluded that the tissue CEA measurement is of help to judge the prognosis.  Positive tissue CEA staining is one of the prognostic factors from a result of this study that the survival time in those who show positive tissue CEA staining is longer than those with negative one.  It is evident that CEA is detected in the normal mucosa. Specificity and significance of CEA as a tumor marker are not made clear yet. The mechanisms of CEA generation, transportation and excretion are concerned in association with cancer specificity.  Further researches should be accumulated to elucidate a CEA character in progression of carcinomas.References 1) Gold P and Freedman SO: Specific carcinoembryonic antigens of the   humans of the human digestive system. J Exp Med 122:467-481, 1965. 2) Oikawa S, Nakazato H and Kosaki G: Primary structure of human   carcinoembryonic antigen (CEA) deduced from cDNA sequence. Bio-  chem Biophys Res Commun 142:511-518, 1987. 3) Thompson JA, Grunert F and Zimmermann W: Carcinoembryonic   Antigen Family: Molecular Biology and clinical perspectives. J Clin   Lab Anal 5:344-366, 1991. 4) Yamashita K, Totani K, Kuroki M et al: Structural studies of the   carcinoembryohydrate moieties of carcinoembryonic antigen. Cancer   Res 47:3451-3459, 1987. 5) Matsuoka Y, Hara M, Takatsu K et al: Presence of antigen related to   the carcinoembryonic antigen in feces of normal adults. Gann   64:203-206, 1978. 6) Shimano T, Inaji H, Tomonaga S et al: The measurement of tumor   marker and its clinical significance. (1) CEA measurement instrument.   Reagent 4:419-423, 1986.

CEA in Esophageal Cancer Tissues

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CEA in Esophageal Cancer Tissues

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