Abstract
Purpose: To evaluate the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with Dukes' B2 and C colon carcinoma. Methods: We conducted a retrospective analysis to evaluate the prognostic value of TS, Ki-67, and p53 in 465 patients with Dukes' B2 (220 patients) or Dukes' C (245 patients) colon carcinoma. Patients represent a nonrandom subset obtained from five randomized phase III trials and were treated with either surgery alone (151 patients) or surgery plus fluorouracil-based chemotherapy (314 patients). All three markers were assayed using immunohistochemical techniques. Results: With a minimum follow-up of 5 years, our retrospective analysis failed to demonstrate a consistent and significant association between TS, Ki-67, or p53 and either disease-free survival or overall survival. Exploratory analyses did not reveal a convincing explanation for these results that are in conflict with the published literature. Notable interactions were observed. In particular, high Ki-67 levels were associated with increased (decreased) survival in patients with low (high) TS intensity. Patients whose tumors stained positively for p53 seemed to benefit substantially from the use of adjuvant chemotherapy compared with those who were not treated (P = .05). Conclusion: This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1735-1743 |
| Number of pages | 9 |
| Journal | Journal of Clinical Oncology |
| Volume | 20 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 1 2002 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer. / Allegra, Carmen J.; Parr, Allyson L.; Wold, Lester E.; Mahoney, Michelle R.; Sargent, Daniel J.; Johnston, Patrick Bruce; Klein, Pam; Behan, Katie; O'Connell, Michael J.; Levitt, Ralph; Kugler, John W.; Tirona, Maria Tria; Goldberg, Richard M.
In: Journal of Clinical Oncology, Vol. 20, No. 7, 01.04.2002, p. 1735-1743.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer
AU - Allegra, Carmen J.
AU - Parr, Allyson L.
AU - Wold, Lester E.
AU - Mahoney, Michelle R.
AU - Sargent, Daniel J.
AU - Johnston, Patrick Bruce
AU - Klein, Pam
AU - Behan, Katie
AU - O'Connell, Michael J.
AU - Levitt, Ralph
AU - Kugler, John W.
AU - Tirona, Maria Tria
AU - Goldberg, Richard M.
PY - 2002/4/1
Y1 - 2002/4/1
N2 - Purpose: To evaluate the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with Dukes' B2 and C colon carcinoma. Methods: We conducted a retrospective analysis to evaluate the prognostic value of TS, Ki-67, and p53 in 465 patients with Dukes' B2 (220 patients) or Dukes' C (245 patients) colon carcinoma. Patients represent a nonrandom subset obtained from five randomized phase III trials and were treated with either surgery alone (151 patients) or surgery plus fluorouracil-based chemotherapy (314 patients). All three markers were assayed using immunohistochemical techniques. Results: With a minimum follow-up of 5 years, our retrospective analysis failed to demonstrate a consistent and significant association between TS, Ki-67, or p53 and either disease-free survival or overall survival. Exploratory analyses did not reveal a convincing explanation for these results that are in conflict with the published literature. Notable interactions were observed. In particular, high Ki-67 levels were associated with increased (decreased) survival in patients with low (high) TS intensity. Patients whose tumors stained positively for p53 seemed to benefit substantially from the use of adjuvant chemotherapy compared with those who were not treated (P = .05). Conclusion: This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome.
AB - Purpose: To evaluate the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with Dukes' B2 and C colon carcinoma. Methods: We conducted a retrospective analysis to evaluate the prognostic value of TS, Ki-67, and p53 in 465 patients with Dukes' B2 (220 patients) or Dukes' C (245 patients) colon carcinoma. Patients represent a nonrandom subset obtained from five randomized phase III trials and were treated with either surgery alone (151 patients) or surgery plus fluorouracil-based chemotherapy (314 patients). All three markers were assayed using immunohistochemical techniques. Results: With a minimum follow-up of 5 years, our retrospective analysis failed to demonstrate a consistent and significant association between TS, Ki-67, or p53 and either disease-free survival or overall survival. Exploratory analyses did not reveal a convincing explanation for these results that are in conflict with the published literature. Notable interactions were observed. In particular, high Ki-67 levels were associated with increased (decreased) survival in patients with low (high) TS intensity. Patients whose tumors stained positively for p53 seemed to benefit substantially from the use of adjuvant chemotherapy compared with those who were not treated (P = .05). Conclusion: This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome.
UR - http://www.scopus.com/inward/record.url?scp=0036534002&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036534002&partnerID=8YFLogxK
U2 - 10.1200/JCO.2002.07.080
DO - 10.1200/JCO.2002.07.080
M3 - Article
C2 - 11919229
AN - SCOPUS:0036534002
VL - 20
SP - 1735
EP - 1743
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 7
ER -