Poorly differentiated clusters predict colon cancer recurrence: An in-depth comparative analysis of invasive-front prognostic markers Journal Article


Authors: Konishi, T.; Shimada, Y.; Lee, L. H.; Cavalcanti, M. S.; Hsu, M.; Smith, J. J.; Nash, G. M.; Temple, L. K.; Guillem, J. G.; Paty, P. B.; Garcia-Aguilar, J.; Vakiani, E.; Gonen, M.; Shia, J.; Weiser, M. R.
Article Title: Poorly differentiated clusters predict colon cancer recurrence: An in-depth comparative analysis of invasive-front prognostic markers
Abstract: This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed. Prognostic accuracies for recurrence-free survival (RFS) were compared, and interobserver agreement among 3 pathologists was assessed. The study cohort consisted of 851 patients. Although all the histologic markers except WHO grade were significantly associated with RFS (PDCs, tumor budding, perineural invasion, and desmoplastic reaction: P<0.001; Crohn-like lymphoid reaction: P=0.021), PDCs (grade 1 [G1]: N=581; G2: N=145; G3: N=125) showed the largest separation of 3-year RFS in the full cohort (G1: 94.1%; G3: 63.7%; hazard ratio [HR], 6.39; 95% confidence interval [CI], 4.11-9.95; P<0.001), stage II patients (G1: 94.0%; G3: 67.3%; HR, 4.15; 95% CI, 1.96-8.82; P<0.001), and stage III patients (G1: 89.0%; G3: 59.4%; HR, 4.50; 95% CI, 2.41-8.41; P<0.001). PDCs had the highest prognostic accuracy for RFS with the concordance probability estimate of 0.642, whereas WHO grade had the lowest. Interobserver agreement was the highest for PDCs, with a weighted kappa of 0.824. The risk of recurrence over time peaked earlier for worse PDCs grade. Our findings indicate that PDCs are the best invasive-front histologic marker in terms of prognostic accuracy and interobserver agreement. PDCs may replace WHO grade as a prognostic indicator. © 2018 Wolters Kluwer Health, Inc.
Keywords: colon cancer; prognostic markers; invasive front; poorly differentiated clusters
Journal Title: American Journal of Surgical Pathology
Volume: 42
Issue: 6
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2018-06-01
Start Page: 705
End Page: 714
Language: English
DOI: 10.1097/pas.0000000000001059
PROVIDER: scopus
PMCID: PMC5943141
PUBMED: 29624511
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Meier Hsu
    169 Hsu
  2. Philip B Paty
    496 Paty
  3. Mithat Gonen
    1028 Gonen
  4. Jose Guillem
    414 Guillem
  5. Jinru Shia
    717 Shia
  6. Martin R Weiser
    534 Weiser
  7. Garrett Nash
    261 Nash
  8. Larissa Temple
    193 Temple
  9. Efsevia Vakiani
    263 Vakiani
  10. Jesse Joshua Smith
    217 Smith
  11. Lik Hang   Lee
    17 Lee