Poorly differentiated clusters as a prognostic marker at the invasive front of colon cancer.

Abstract

621 Background: Histology at the invasive front of colon cancer can predict malignant potential. However, the optimal histological marker is yet to be established. This study compares the various invasive front histologic markers. Methods: A single-institution prospective database was queried for consecutive patients who underwent curative resection for Stage I-III colon adenocarcinoma from 2007-14. Histologic features were reviewed by a pathologist, including poorly differentiated clusters (PDC), tumor budding (BD), perineural invasion (PN), desmoplastic reaction (DR) and Crohn’s like reaction (CLR) at the invasive front, and WHO grade of the whole tumor. PDC was defined as cancer clusters of ≥ 5 cancer cells that lack a gland-like structure, and was graded into G1 ( < 5), G2 (5-9) and G3 ( ≥ 10) by the highest number of the clusters /HPF. Clinical outcome included recurrence free survival (RFS) and peak hazard function of recurrence and death identified using the kernel-smoothing method. Predictive accuracy was measured with concordance probability estimate (CPE) for proportional hazards regression. Inter-observer agreement was assessed by weighted kappa values on diagnoses rendered by 3 pathologists on 50 randomly selected cases. Results: The study cohort consisted of 851 patients with a median follow up of 36 months. PDC, BD, PN, DR and CLR at the invasive front were significantly associated with RFS. When analyzed by stage, PDC, BD and PN were associated with RFS both in Stage II and Stage III, while the others were prognostic only in Stage III. CPE was the highest in PDC (0.642), indicating the best predictive accuracy, while it was the lowest in WHO grade (0.526). Weighted kappa was also the highest for PDC, indicating the best inter-observer agreement (PDC: 0.824, WHO grade: 0.568). The smoothed graph of the hazard function showed that the risk of recurrence was not only the highest but peaked earlier for PDC G3 (between0 and 12 months) than PDC G2 (between12 and 24 months) and G1 (no evident peak). Conclusions: Of the commonly evaluated histologic markers at the invasive front, PDC grade is the most predictive and reproducible. Further confirmatory investigations are warranted to determine if PDC can replace WHO grade.