Poorly differentiated clusters with larger extents have a greater impact on survival: a semi-quantitative pathological evaluation for 239 patients with non-mucinous pT2-3 colorectal carcinoma

BACKGROUND Poorly differentiated clusters (PDCs) at the invasive front of tumors in colorectal cancer (CRC) have recently been highlighted as histological prognosticators. We aimed to assess the clinical importance of extent of PDCs in CRC. METHODS A total of 239 patients with non-mucinous pT2 and pT3 CRC were pathologically reviewed. PDCs were defined as cancer clusters composed of ≥5 cancer cells lacking full glandular formation. Patients were classified according to the number of PDCs observed under a × 20 objective lens. Patients with <5 clusters were classified as G1, those with 5 to 9 clusters were classified as G2, and those with ≥10 clusters were classified as G3. In addition, in order to semi-quantitatively evaluate the PDCs, the extent of the highest grade of PDCs at the tumor's invasive front was measured and summated, if separately distributed. We identified cutoffs for the extents of PDCs and compared the results with the patients' survival rates. RESULTS The number of patients with G1, G2, and G3 clusters was 140, 46, and 53, respectively. The presence of G3 PDCs was significantly correlated with lymphatic permeation (P < 0.0001) and node involvement (P < 0.0001). The 5-year overall survival rates of G1, G2, and G3 were 91%, 88%, and 76%, respectively. Based on the Kaplan-Meier method, 5- and 10-mm cutoffs were identified as the statistically reliable stratification for the extents of G3 clusters, and 15, 20, and 18 G3 patients exhibited extents of <5 mm, 5 to 9 mm, and ≥10 mm, respectively; however, cutoffs for the extents of G1 and G2 clusters were not obtained. In the subgroup analysis, when the extents of G3 clusters were subclassified into <5 mm as G3a, 5 to 9 mm as G3b, and ≥10 mm as G3c, the 5-year overall survival rates were 83%, 62%, and 44%, respectively. CONCLUSIONS G3 PDCs were highly indicative of tumor aggressiveness. Quantitative evaluation that takes into account the extent of PDCs would provide more concise prognostic information. Our results suggest that G3 PDCs with a larger extent are closely associated with unfavorable patient outcome.