Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer

Carmen J. Allegra, Allyson L. Parr, Lester E. Wold, Michelle R. Mahoney, Daniel J. Sargent, Patrick Bruce Johnston, Pam Klein, Katie Behan, Michael J. O'Connell, Ralph Levitt, John W. Kugler, Maria Tria Tirona, Richard M. Goldberg

Research output: Contribution to journalArticle

150 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1735-1743
Number of pages9
JournalJournal of Clinical Oncology
Volume20
Issue number7
DOIs
StatePublished - Apr 1 2002

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Thymidylate Synthase
Colonic Neoplasms
Colon
Carcinoma
Survival
Adjuvant Chemotherapy
Fluorouracil
Disease-Free Survival
Staining and Labeling
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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 journalArticle

Allegra, CJ, Parr, AL, Wold, LE, Mahoney, MR, Sargent, DJ, Johnston, PB, Klein, P, Behan, K, O'Connell, MJ, Levitt, R, Kugler, JW, Tirona, MT & Goldberg, RM 2002, 'Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer', Journal of Clinical Oncology, vol. 20, no. 7, pp. 1735-1743. https://doi.org/10.1200/JCO.2002.07.080
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. / Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 7. pp. 1735-1743.
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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.

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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.

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