DNA image cytometry predicts disease outcome in stage II colorectal carcinoma

Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to study the prognostic value of nuclear DNA content in stage II CRC of patients with long-term followup.

Isolated nuclei from 50 microm-thick paraffin sections of tissue samples from 253 patients with stage II CRC, who had undergone bowel resection at Turku University Central Hospital were cytocentrifuged on slides, stained with Feulgen staining, and DNA was measured using a computer-assisted image analysis cytometry system. Different approaches were applied in analysis of DNA histograms.

DNA content did not show any relation with age (p < 0.96), sex (p < 0.35), tumor invasion (p < 0.77), or grade (p < 0.31). Aneuploid DNA content was significantly more frequent in the cancer of the left colon and rectum than the right colon (p = 0.02). S-phase fraction analysis revealed that a higher proportion (62%) of the older patients (>65 years) had high proliferation rates than did the younger patients (p < 0.05). Patients with narrow range histograms had a better disease-free survival (DFS) (narrow range: 70%, wide range: 60% at 10 years). Tumors with >9c nuclei were associated with significantly better DFS and disease-specific survival (DSS) as compared with the patients who did not have >9c nuclei in their tumor samples (p < 0.003 and p < 0.0001, respectively). Multivariate survival (Cox) model showed that only classification of the basic pattern of the histogram [odds ratio OR) = 29.14; 95% confidence interval (CI) 2.350-361.57] (p = 0.009) and recurrence (OR = 165.35; 95% CI 48.42-564.7) (p = 0.0001) proved to be independent predictors of clinical outcome.

Our results seem to suggest it truly is possible, by using DNA cytometry, to find groups with different prognosis among stage II cases. Those with a high recurrence rate should be considered for adjuvant chemotherapy.