Ki-67 and CEA expression as prognostic markers in Dukes' C colorectal cancer

doi:10.1016/j.canlet.2003.10.032

Cancer Letters

Volume 207, Issue 1, 15 April 2004, Pages 109-115

https://doi.org/10.1016/j.canlet.2003.10.032 Get rights and content

Abstract

This study investigated the relationship between clinicopathological or immunohistochemical factors and postoperative prognosis for Dukes' C colorectal cancer. Short-term survivors died from cancer within 2 years of surgery, whereas long-term survivors were disease-free for over 10 years. The groups differed in Ki-67 antigen and CEA expression in colon cancer, and CEA expression in rectal cancer that was limited to the metastatic lymph nodes. The immunohistochemical scores were higher in short-term survivors. Our data suggest that the characteristics of metastatic lymph nodes are important as a predictor of the aggressiveness of tumor behavior and that the expression of Ki-67 antigen or CEA there may be a useful indicators of patients' survival in Dukes' C colorectal cancer.

Introduction

The prognosis of patients with Dukes' C colorectal cancer has recently been improving [1]. However, there have been some cases of recurrence and death within a short period following a curative operation. In order to evaluate the prognostic factors in such patients, we compared clinicopathological and immunohistochemical factors between these patients and the patients with longer survival rates. Most studies evaluating immunohistochemical factors in primary colorectal cancer lesions have failed to indicate any correlation with prognosis [2], [3], [4], [5], [6], [7], whereas Ki-67 antigen expression in colorectal liver metastasis has been demonstrated to be an indicator of patients' survival [8]. Thus, we investigated the immunohistochemical scores not only in the primary tumors, but also in the metastatic lymph nodes. Our goal was to determine if either of these biological parameters could be used to predict the outcome of the patient's disease, and whether primary tumor or metastatic lymph nodes are useful as predictors of aggressive tumor behavior.

Section snippets

Subjects

Between January 1985 and December 2000, 234 patients with Dukes' C colorectal cancer underwent curative surgery at Sakai Municipal Hospital. Of these, 144 patients had colon cancer and 90 patients had rectal cancer. The 5-year survival rates of the patients with colon and rectal cancer are 70.1 and 45.4%, respectively. Four patients died due to recurrence of cancer within 1 year, 21 patients died within 2 years, and 40 patients died within 3 years of surgery. Sixty-four patients were

Backgrounds

The median survival time of the short-term and long-term survivors was 505 and 4150.5 days, respectively.

Of the short-term survivors, 11 patients had colon cancer and 10 patients had rectal cancer. In the case of colon cancer patients, the median time from operation to recurrence was 215.5 days. The first metastatic sites were the lungs (3 patients), liver (2 patients), peritoneum (2 patients), multiple organs (2 patients), and not known (2 patients). Nine patients received chemotherapy, 1

Discussion

Among the clinicopathological factors examined, only age at surgery was significantly different between the short-term and long-term survivors in both colon and rectal cancer. If the patients who were disease-free for over 5 years are considered as the long-term survivors, the significant difference that was observed in age at surgery between the two groups disappears. This might be due to the fact that life expectancy is shorter in older patients so survival for over 10 years postoperatively

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Ki-67 proliferative index has a prognostic and/or predictive value in different tumor types, however in colorectal cancer the results seem to be conflicting (Aoki et al., 1998; Ishida et al., 2004; Kimura et al., 2000; Kyzer and Gordon, 1997; Ofner et al., 1996; Palmqvist et al., 1999). Namely, Ki-67 cannot be correlated with the clinic and pathologic parameters that define CRC (location, age, sex, degree of differentiation, etc.), although a strong statistically significant correlation can be found with development of metastases (Aoki et al., 1998; Ishida et al., 2004; Kimura et al., 2000; Kyzer and Gordon, 1997; Ofner et al., 1996; Palmqvist et al., 1999). Therefore, Ki-67 has a limited usage as discriminatory prognosis factor in CRC.
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Interestingly, this set of CRC samples also exhibited a normal E-cadherin staining and a nuclear localization of β-catenin together with higher proliferation levels as estimated by Ki-67 labeling index. Although the use of Ki-67 antigen as prognostic marker is quite controversial in CRC, a recent report has demonstrated that, at least for Dukes' C cases, levels of immunohistochemical positivity for this antigen correlate with the clinical outcome of affected patients [26,27]. The remaining set of analyzed CRCs (29%) showed, on the contrary, a virtually normal expression of μ-protocadherin accompanied by retention of β-catenin on cell membrane of cancer cells and a lower proliferation activity.
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Ki-67 and CEA expression as prognostic markers in Dukes' C colorectal cancer

Abstract

Introduction

Section snippets

Subjects

Backgrounds

Discussion

Surg. Oncol.

Eur. J. Surg. Oncol.

Colorectal cancer statistics in Japan: data from JSCCR registration, 1974–1993

Int. J. Clin. Oncol.

Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis

Cancer

Heterogeneity in proliferation markers in colorectal cancer

Anticancer Res.

MIB1 in colorectal carcinoma: its evaluation by three different methods reveals lack of prognostic significance

Anal. Cell. Pathol.

Ki-67 expression in relation to clinicopathological variables and prognosis in colorectal adenocarcinomas

Acta Pathol. Microbiol. Immunol. Scand.

Determination of proliferative activity in colorectal carcinoma using monoclonal antibody Ki67

Dis. Colon Rectum

TNM Classification of Malignant Tumors