Low tumour cell proliferation at the invasive margin is associated with a poor prognosis in Dukes’ stage B colorectal cancers

Abstract

SummaryThe conflicting results about the prognostic impact of tumour cell proliferation in colorectal cancer might be explained by the heterogeneity observed within these tumours. We have investigated whether a systematic spatial heterogeneity exists between different compartments, and whether the presence of such a systematic heterogeneity has any impact on survival. Fifty-six Dukes' stage B colorectal cancers were carefully morphometrically quantified with respect to the immunohistochemical expression of the proliferative marker Ki-67 at both the luminal border and the invasive margin. The proliferative activity was significantly higher at the luminal border compared with the invasive margin (P < 0.001), although the two compartments were also significantly correlated with each other. Tumours with low proliferation at the invasive margin had a significantly poorer prognosis both in univariate (P = 0.014) and in multivariate survival analyses (P = 0.042). We conclude that Dukes' B colorectal cancers exhibit a systematic spatial heterogeneity with respect to proliferation, and tumours with low proliferation at the invasive margin had a poor prognosis. The present data independently confirm recent results from the authors, and provide new insights into the understanding of tumour cell proliferation in colorectal cancer.

Clinical Significance of Preoperative Serum Sialic Acid Levels in Colorectal Cancer: Utility in the Detection of Patients at High Risk of Tumor Recurrence

“…At present, the Dukes' stage of the tumor is the most commonly used predictor of tumor recurrence in colorectal cancer (1,(24)(25)(26). However, the information provided by Dukes' stage is only available postoperatively, and considerable variation in prognosis has been demonstrated within each stage (27,28). Therefore, according to our findings preoperative serum TSA and TSA/TP levels could represent additional prognostic markers for colorectal cancer that are available before surgery.…”

“…Of the two markers studied, only TSA/TP allowed the differentiation of two groups of patients with different clinical outcomes within Dukes' stage B. This result is of interest since Dukes' stage B tumors account for more than one-third of all colorectal cancer cases and, although these tumors are pathologically homogeneous, they exhibit clinical heterogeneity (27,28). In fact, some patients in Dukes' stage B have been described to have a poorer prognosis than patients in Dukes' stage C (29).…”

Immunohistochemical Expression of Ki67 and HER2 in Colorectal Cancer Compared to Adenomatous and Normal Samples

“…Salminen et al reported that the high proliferation activity of Ki67 was associated with increased survival rate of patients with CRC (35). In addition, Melling et al and Palmqvist et al found that the low expression of Ki67 index was associated with poor prognosis and metastasis of cancer cells and its higher expression was seen in normal colorectal tissues compared to the CRCs (15,36). On the other hand, it has been shown in several studies that the high expression of Ki67 was associated with poor prognosis at the higher stages of cancer in prostate and gastrointestinal tumors, endocrine malignancies, and breast cancer (17,18,37).…”

Slow proliferation as a biological feature of colorectal cancer metastasis

“…It is noteworthy that budding cells have undergone an epithelialmesenchymal transition (EMT) and are growth arrested due to increased expression of the cell-cycle-dependent kinase inhibitor, P16 and other unknown mechanisms (Jung et al, 2001). Furthermore, low cellular proliferation at the invasive margin has been associated with poor prognosis in CRC (Palmqvist et al, 1999). Therefore, CRCs with a high proportion of dedifferentiated cells or with an extensive tumour -host interface may be more slowly proliferating but aggressive.…”