p53 and thymidylate synthase expression in untreated stage II colon cancer: associations with recurrence, survival, and site

• Published in: Clinical cancer research Vol. 4; no. 5; pp. 1227 - 1234
• Main Authors: LENZ, H.-J, DANENBERG, K. D, LEICHMAN, C. G, FLORENTINE, B, JOHNSTON, P. G, GROSHEN, S, LINYUN ZHOU, YI PING XIONG, DANENBERG, P. V, LEICHMAN, L. P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-05-1998
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Colonic Neoplasms - enzymology; Colonic Neoplasms - metabolism; Colonic Neoplasms - mortality; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Proteins - metabolism; Neoplasm Recurrence, Local; Neoplasm Staging; Retrospective Studies; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Analysis; Thymidylate Synthase - metabolism; Tumor Suppressor Protein p53 - metabolism; Tumors; Human; Immunohistochemistry; Relapse; Right colon; Prognosis; Enzyme; Transferases; Exploration; Malignant tumor; Thymidylate synthase; Survival; Retrospective; Colonic disease; Pathology; TP53 Gene; Methyltransferases; Digestive diseases; Intestinal disease; Colon; Left colon; Localization; Tumor suppressor gene
• ISSN: 1078-0432; 1557-3265

We initiated a retrospective study to determine whether p53 status and thymidylate synthase (TS) protein expression in primary
colon tumors influence recurrence and survival for patients with stage II colon cancer. Tumor specimens from 45 consecutive
untreated patients with stage II colon cancer were examined for p53 and TS protein expression using immunohistochemistry.
The median follow-up was 5.1 years. Eighteen patients had left-sided tumors, and 27 had right-sided tumors. Fourteen of 45
patients (31%) developed recurrence. p53 overexpression was detected in the tumors of 18 patients (40%); 10 patients (55%)
with p53 overexpression recurred; and 4 of 27 (15%) without evidence of p53 overexpression recurred (P = 0.002). High TS expression
was detected in the tumors of 16 patients (36%): 8 patients (50%) with high TS expression recurred, and 6 patients (21%) with
low TS expression recurred (P = 0.027). Patients with p53 overexpression had a significantly poorer survival than did those
patients without p53 overexpression (P < 0.001). High TS expression was associated with poor survival (P = 0.004). p53 overexpression
and high TS expression were significantly associated with left-sided tumors (P = 0.003 and P = 0.022). Thirteen of 16 patients
(81%) with high TS expression also overexpressed p53, and 24 of 29 patients (81%) with low TS expression did not manifest
p53 overexpression (P < 0.001). p53 and TS expression in primary stage II colon cancer are associated and appear to influence
recurrence and survival. In this pilot study, left-sided tumors demonstrate significantly more p53 overexpression and significantly
higher TS expression than do right-sided tumors, which may explain the significantly poorer survival for patients with left-sided
tumors.