J Korean Surg Soc.  2013 Dec;85(6):283-289. 10.4174/jkss.2013.85.6.283.

Clinical utility of tumor marker cutoff ratio and a combination scoring system of preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4 levels in gastric cancer

• Lee JC
• Lee SY
• Kim CY
• Yang DH

• KMID: 2212551
• DOI: http://doi.org/10.4174/jkss.2013.85.6.283

Abstract

PURPOSE
The present study is to investigate the clinical utility of tumor marker cutoff ratio (TMR) and develop a TMR combination scoring system based on preoperative tumor marker (TM) levels to prognosis prediction in gastric cancer.
METHODS
We include 1,142 patients for whom two or more TMs were measured and who underwent radical gastrectomy between 1990 and 2003.
RESULTS
Five-year risk of recurrence (5 YRR) for carcinoembryonic antigen (CEA) TMRs were 18.3%, 29.8%, 61.4% for TMR < 1.0, 1.0 < or = TMR < 2.0, TMR > or = 2.0 respectively. 5 YRR for carbohydrate antigen 19-9 (CA 19-9) TMR were 19.7%, 35.6%, 58.4% for TMR < 1.0, 1.0 < or = TMR < 3.0, TMR > or = 3.0, respectively. 5 YRR for carbohydrate antigen 72-4 (CA 72-4) TMR were 15.2% and 33.6% for TMR < 1.0 and TMR > or = 1.0, respectively. We defined high TMR (TMR > or = 2.0 for CEA, TMR > or = 3.0 for CA19-9), low TMR (1.0 < or = TMR < 2 for CEA, 1.0 < or = TMR < 3.0 for CA 19-9 and 1.0 < or = TMR for CA72-4) and negative TMR (TMR < 1.0 for all TMs). A TMR combination scoring system was devised with negative scored as zero points, low as 1 and high as 2 for each TMR. TMR scores were divided into four categories (score 0, 1, 2, 3 and above) based on the calculated TMR score and 5 YRR were found to be 12.8%, 23.9%, 45.5%, and 68.3%, respectively (P < 0.05). Multivariate analysis showed that our scoring system was a significant independent prognostic factor.
CONCLUSION
Preoperative TMRs such as CEA, CA 19-9, and CA 72-4 show a correlation with prognosis and the TMR combination scoring system could be a useful tool for the prediction of prognosis in gastric cancer.

Keyword

Gastric cancer; Prognosis; Tumor markers

MeSH Terms

Biomarkers, Tumor
Carcinoembryonic Antigen*
Cinnarizine
Gastrectomy
Humans
Multivariate Analysis
Prognosis
Recurrence
Stomach Neoplasms*
Carcinoembryonic Antigen
Cinnarizine

Figure

• 

  Fig. 1 Diagram of patient selection. CEA, carcinoembryonic antigen; CA 19-9, carbohydrate antigen 19-9; CA 72-4, carbohydrate antigen 72-4; TM, tumor marker.

• 

  Fig. 2 Correlation of each stage and tumor marker cutoff ratio. There was a tendency toward increasing tumor marker levels with advancing cancer stage with (A) carcinoembryonic antigen (CEA) being positive in 6.1% of stage I, 16,7% in stage II, 19.9% in stage III, and 24.7% in stage IV cancers (P < 0.001). (B) For carbohydrate antigen 19-9 (CA 19-9), a similar increasing pattern was found with 4.0% positive in stage I, 6.8% in stage II, 13.9% in stage III, and 24.1% in stage IV cancers (P < 0.001). (C) Carbohydrate antigen 72-4 (CA 72-4) exceeded our defined threshold in 7.4% of stage I, 16.7% of stage II, 13.1% of stage III, and 33.3% of stage IV cancers, but there were no significant differences between the stages (P = 0.085). CI, confidence interval.

• 

  Fig. 3 Risk of recurrence by tumor marker cutoff ratio (TMR) of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and carbohydrate antigen 72-4 (CA 72-4). (A) CEA shows significant difference in 5-year risk of recurrence between the TMR < 1.0, 1.0 ≤ TMR < 2.0, and 2.0 ≤ TMR groups, with results of 18.3%, 29.8%, 61.4% (P < 0.001). (B) CA 19-9 shows 5-year risk of recurrence of 19.7%, 35.6%, 58.4% between the TMR < 1.0, 1.0 ≤ TMR < 3.0, and 3.0 ≤ TMR groups, respectively with significant difference (P < 0.001). (C) CA 72-4 shows significant difference between the TMR (<1.0) group and groups with TMR higher than 1.0, resulting in of 15.2% and 33.6%, respectively (P < 0.001). NS, nonspecific.

• 

  Fig. 4 Risk of recurrence according to the tumor marker cutoff ratio (TMR) combination scoring system. TMR combination scoring system (the sum of the scores) was divided into four categories (score 0, score 1, score 2, score 3 and above). Five-year risk of recurrence for each category were 12.8%, 23.9%, 45.5%, and 68.3%, respectively (P < 0.05).

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