Tumor budding in colorectal carcinoma: Confirmation of prognostic significance and histologic cutoff in a population-based cohort

Rondell Graham, Robert A. Vierkant, Lori S. Tillmans, Alice H. Wang, Peter W. Laird, Daniel J. Weisenberger, Charles F. Lynch, Amy J. French, Susan L Slager, Yassaman Raissian, Joaquin J. Garcia, Sarah E. Kerr, Hee Eun Lee, Stephen N Thibodeau, James R Cerhan, Paul John Limburg, Thomas Christopher Smyrk

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Abstract

Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for "high" tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between 2 gastrointestinal pathologists and a group of 4 general surgical pathologists. High budding (≥ 10 tumor buds in a ×20 objective field) was present in 32% of cases, low budding in 46%, and no budding in 22%. High tumor budding was associated with advanced pathologic stage (P < 0.001), microsatellite stability (P=0.005), KRAS mutation (P=0.010), and on multivariate analysis with a >2 times risk of cancer-specific death (hazard ratio=2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer-specific death. The interobserver agreement was good with weighted k of 0.70 for 2 gastrointestinal pathologists over 121 random cases and 0.72 between all 6 pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown that a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports.

Original languageEnglish (US)
Pages (from-to)1340-1346
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume39
Issue number10
StatePublished - Oct 1 2015

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Colorectal Neoplasms
Population
Neoplasms
Hematoxylin
Eosine Yellowish-(YS)
Coloring Agents
Pathologists

Keywords

  • Bud count
  • Colorectal carcinoma
  • Cutoff
  • KRAS
  • Poor prognosis
  • Tumor budding

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Graham, R., Vierkant, R. A., Tillmans, L. S., Wang, A. H., Laird, P. W., Weisenberger, D. J., ... Smyrk, T. C. (2015). Tumor budding in colorectal carcinoma: Confirmation of prognostic significance and histologic cutoff in a population-based cohort. American Journal of Surgical Pathology, 39(10), 1340-1346.

Tumor budding in colorectal carcinoma : Confirmation of prognostic significance and histologic cutoff in a population-based cohort. / Graham, Rondell; Vierkant, Robert A.; Tillmans, Lori S.; Wang, Alice H.; Laird, Peter W.; Weisenberger, Daniel J.; Lynch, Charles F.; French, Amy J.; Slager, Susan L; Raissian, Yassaman; Garcia, Joaquin J.; Kerr, Sarah E.; Lee, Hee Eun; Thibodeau, Stephen N; Cerhan, James R; Limburg, Paul John; Smyrk, Thomas Christopher.

In: American Journal of Surgical Pathology, Vol. 39, No. 10, 01.10.2015, p. 1340-1346.

Research output: Contribution to journalArticle

Graham, R, Vierkant, RA, Tillmans, LS, Wang, AH, Laird, PW, Weisenberger, DJ, Lynch, CF, French, AJ, Slager, SL, Raissian, Y, Garcia, JJ, Kerr, SE, Lee, HE, Thibodeau, SN, Cerhan, JR, Limburg, PJ & Smyrk, TC 2015, 'Tumor budding in colorectal carcinoma: Confirmation of prognostic significance and histologic cutoff in a population-based cohort', American Journal of Surgical Pathology, vol. 39, no. 10, pp. 1340-1346.
Graham, Rondell ; Vierkant, Robert A. ; Tillmans, Lori S. ; Wang, Alice H. ; Laird, Peter W. ; Weisenberger, Daniel J. ; Lynch, Charles F. ; French, Amy J. ; Slager, Susan L ; Raissian, Yassaman ; Garcia, Joaquin J. ; Kerr, Sarah E. ; Lee, Hee Eun ; Thibodeau, Stephen N ; Cerhan, James R ; Limburg, Paul John ; Smyrk, Thomas Christopher. / Tumor budding in colorectal carcinoma : Confirmation of prognostic significance and histologic cutoff in a population-based cohort. In: American Journal of Surgical Pathology. 2015 ; Vol. 39, No. 10. pp. 1340-1346.
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