Metastatic pattern in colorectal cancer is strongly influenced by histological subtype

Abstract

Background: Clinical studies regarding colorectal cancer (CRC) have suggested differences in metastatic patterns between mucinous adenocarcinoma (MC), signet-ring cell carcinoma (SRCC) and the more common adenocarcinoma (AC). The current study systematically evaluates metastatic patterns of different histological subtypes in CRC patients and analyzes metastatic disease upon primary tumor localization.

Patients and methods: A nationwide retrospective review of pathological records of 5817 patients diagnosed with CRC who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA). To substantiate clinical relevance, metastatic patterns were compared with the prospective randomized multicenter Total Mesorectal Excision (TME) trial, which investigated efficacy of preoperative radiotherapy in rectal cancer patients.

Results: In the autopsy study, 1675 patients had metastatic disease. MC and SRCC patients more frequently had metastatic disease (33.9% and 61.2% versus 27.6%; P < 0.0001) and had metastases at multiple sites more often compared with AC patients (58.6% and 70.7% versus 49.9%; P = 0.001). AC predominantly metastasized to the liver, and MC and SRCC more frequently had peritoneal metastases. Metastatic patterns were also related to the primary tumor site, with a high rate of abdominal metastases in colon cancer patients, whereas rectal cancer patients more often had metastases at extra-abdominal sites. Results from the TME trial confirmed findings in rectal cancer patients from the autopsy study.

Conclusion: There are profound differences in metastatic patterns between histological subtypes and the localization of the primary tumor in CRC. Findings from this study should encourage to take these factors into account for follow-up strategies and future studies.

Keywords: colorectal cancer; metastases; mucinous adenocarcinoma; signet-ring cell carcinoma.

Figure 1.

(A) Distribution of metastases according to histology. AC, adenocarcinoma, MC, mucinous adenocarcinoma, SRCC, signet-ring cell carcinoma, LN, lymph node. **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. (B) Distribution of metastases according to tumor site. LN, lymph node. *P ≤ 0.05, ****P ≤ 0.0001.

Figure 2.

(A) Relative frequencies of combinations with liver metastases in AC, MC and SRCC patients, P < 0.0001. (B) Relative frequencies of combinations with lung metastases in AC, MC and SRCC patients, P = 0.75. (C). Relative frequencies of combinations with peritoneal metastases in AC, MC and SRCC patients, P < 0.0001.

Figure 3.

Distribution of metastases in rectal cancer patients from the TME-trial and autopsy study. AC, adenocarcinoma, MC, mucinous adenocarcinoma, LN, lymph node. *P ≤ 0.05, **P ≤ 0.01, ****P ≤ 0.0001.