carcinoembryonic antigen (CEA) takes credit for being the first tumor to be tested for colon cancer in 1965 (1). Since then, CEA has been explored extensively.
PREOPERATIVE CARCINOEMBRYONIC ANTIGEN; A PROGNOSTIC INDICATOR OF TUMOR GRADE, LYMPH NODE METASTASES AND STAGING Satkunan M, DZ Andee, Z Zaidi, S Hassan Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia
INTRODUCTION Colorectal carcinoma (CRC) is the commonest gastrointestinal malignancy in Malaysia as well as across the globe. In the domain of gastrointestinal surgery, colorectal cancer along with stomach cancer is the two most extensively researched malignancies. While the human chorionic gonadotropin (HCG) takes credit for being the first tumor marker in modern medicine, carcinoembryonic antigen (CEA) takes credit for being the first tumor to be tested for colon cancer in 1965 (1). Since then, CEA has been explored extensively. It is widely accepted that CEA is not recommended as a screening tool (2). Hence there is interest among researchers to study CEA for its role to prognosticate patients with colorectal cancer in the pre-operative period. Though CEA is used to dictate the overall prognosis, there is little evidence to show the ability of pre- operative CEA to predict tumor grade.
Characteristics Age (Median)
Total n= 20 50.3 years
Percentage
8 12
40% 60%
Sex a. Male b. Female Total Race a. Malay b. Chinese Total CEA a. 5ng/ml Total Tumor Grade a. Well differentiated Adenocarcinoma b. Moderately differentiated Adenocarcinoma c. Signet Ring Cell Carcinoma Total LN status a. Positive b. Negative Total Stage a. stage 1 b. stage 2 c. stage 3 d. stage 4 Total
20 19 1
95% 5% 20
7 13
35% 65% 20
1 18 1
5% 90% 5% 20
15 5
75% 25% 20
1 4 9 6
5% 20% 45% 30% 20
Distant Metastasis
6
30%
Table 1: Clinico- pathological Characteristics
METHODOLOGY This a retrospective analysis of patients diagnosed to have colorectal cancer from 1st January 2013 to 31st December 2013 in Hospital Universiti Sains Malaysia. A total of 20 patients were diagnosed to have CRC and were included in this review. Pre- operative CEA was taken in all patients and they all underwent surgical resection. Their histopathology reports were reviewed with particular interest in tumor grade and lymph node harvest in association with the pre- operative CEA.
Raised CEA levels (>5ng/ml) Tumor Grade a. Well differentiated b. Moderately differentiated c. Signet Ring Cell Total
n= 13
Percentage
0
100%
13 0
A total of 20 patients were recruited in this study. Patient demographics, pre- operative CEA, tumor grade, lymph node harvest and overall staging of the study subjects were collected and tabulated in the table below (Table 1). A raised CEA was taken as levels exceeding 5ng/ml. There were thirteen patients (65%) found to have raised CEA levels. Tumor grades were classified as well differentiated, moderately differentiated, poorly differentiated, signet ring carcinoma as well mucinous cell carcinoma. Majority of our patients amounting to 18 in number (90%) were found to have moderately differentiated adenocarcinoma while one (5%) had well differentiated and one (5%) had signet ring carcinoma. Among patients with raised CEA levels, 77% of them were found to have lymph node metastasis. In patients with elevated CEA, six were diagnosed to have stage III (46%), four patients diagnosed with stage IV disease (31%), two with stage II disease (15%) and one with stage 1 disease (8%).
Tumor Grade a. Well differentiated b. Moderately differentiated c. Signet Ring Cell Total
Percentage
1 5
14% 72% 14%
1 7
77% 23%
10 3
Lymph Node Metastasis a. Positve b. Negative Total
3 4
Stage a. I b. II c. III d. IV Total
0 2 3 2
43% 57% 7
13 Stage a. I b. II c. III d. IV Total
1 2 6 4
8% 15% 46% 31% 13
29% 42% 29% 7
Table 3: Incidence of Tumor Grade, Lymph node metastasis and Disease stage in patients with normal CEA
DISCUSSION CEA is a glycoprotein made up of 60% carbohydrate with a molecular weight of 180- 200 kDA (3). Following its discovery more than 40 years later CEA continues to be one of the most used tumor marker in surgery and the most used tumor marker in colorectal surgery. There has extensive reviews conducted in attempts to co- relate CEA with tumor stage, tumor grade and overall prognosis. An early study done by Wanebo and colleagues demonstrated the correlation between raised CEA levels with advancing stage of CRC (4). In relation with tumor grade, Bhatnagar et al showed that well differentiated tumors produced more CEA when compared to moderate and poorly differentiated tumors (5). In our series of patients, we find raised CEA levels to be associated with moderately differentiated tumors as opposed to that of Bhatnagar and colleagues. At present, there is little data associating raised CEA levels and lymph node metastasis. The available data seem to vary between institutions. Ladenson and colleagues report the incidence of an elevated CEA in Duke’s C stage to be 45% while a review by Wang et al reports the incidence to be at 71% (6, 7). In our review, we find the incidence of lymph nodes in patients with raised level to be as high as 77% which further validates the role of preoperative CEA in prognosticating patients with CRC. With respect to disease staging, majority of our patients with elevated preoperative CEA were found to have stage III and stage IV disease (77%) upon pre- surgery staging. This confirms and supports other evidences that a high preoperative CEA is associated with a poorer disease staging (8). In conclusion, our study supports the use of CEA as a preoperative indicator of tumor grade, stage and lymph node metastasis. A raised preoperative CEA has likelihood of presenting with a higher tumor grade, lymph node metastasis and a poorer disease stage. Therefore, from our study we find the use of preoperative CEA to be a good indicator of the aggressiveness of the disease.
REFERENCES 1) 2) 3) 4) 5) 6) 7) 8)
n= 7
13
Lymph Node Metastasis a. Positve b. Negative Total
Table 2: Incidence of Tumor Grade, Lymph node metastasis and Disease stage in patients with elevated CEA
RESULT
Raised CEA levels (>5ng/ml)
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