The Significance of Tumor Markers for Proliferation and Apoptosis in Predicting Survival in Colorectal Cancer

Hilska, Marja; Collan, Yrjö; Laine, V.; Kössi, Jyrki; Hirsimäki, Pirkko; Laato, Matti; Roberts, Peter

doi:10.1007/s10350-005-0202-x

Cited by 65 publications

(63 citation statements)

References 43 publications

(45 reference statements)

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“…This fact suggests a different behaviour for telomerase depending on its localization ( Table 2). The findings of the present study are in accordance with other studies that identified differences in the etiologic, pathologic, and clinical behaviour of colon and rectal tumours: local recurrence occurs more frequently in patients with rectal cancer, and distant metastases occur more frequently in patients with colon cancer [73][74][75] . It is, therefore, reasonable to suggest that the etiologic factors and molecular bases may differ between colon and rectal cancers [72] .…”

Section: Telomerase As a Colorectal Cancer Markersupporting

confidence: 92%

Telomere function in colorectal cancer

Frías

Morán²,

Juan³

et al. 2009

WJGO

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Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.

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Section: Telomerase As a Colorectal Cancer Markersupporting

confidence: 92%

Telomere function in colorectal cancer

Frías

Morán²,

Juan³

et al. 2009

WJGO

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“…We observed an expression of p53 in 63% of the colorectal carcinomas which is in line with previous studies, where a range of 40 to 81% p53 positivity was found (10)(11)(12)(13). This wide range depends on different techniques used in these studies, such as different antibodies, scoring systems, cutoff-values and study populations.…”

Section: Discussionsupporting

confidence: 91%

“…Other studies reported an unfavourable prognosis in patients with p53-positive carcinomas (12,13,(24)(25)(26)(27)(28), but only few multivariate analyses yielded a significant result in these studies (25). However, other authors did not found a correlation of p53 and prognosis (11,16,29,30). Additionally, we observed that patients with p53-positive carcinomas tended to have a better recurrence-free survival.…”

Section: Discussioncontrasting

confidence: 55%

Combination of p53 expression and p21 loss has an independent prognostic impact on sporadic colorectal cancer

Noske

Lipka²,

Budczies³

et al. 2009

Oncol Rep

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Abstract. There is no clear evidence on the prognostic and predictive value of abnormal p53 expression in colorectal cancer. The major downstream protein, p21, a cell cycle inhibitor, is transcriptionally regulated by p53. The prognostic impact of p21 expression in colorectal carcinomas is still under debate. In this study, we investigated the expression of p21 and p53 in a prospective cohort of 116 sporadic colorectal carcinomas at UICCII/III stage. We observed an expression of p21 in 26% and p53 in 63% of the carcinomas by immunohistochemistry. Patients with p21-negative colorectal carcinomas had a significant better recurrence-free and overall survival than patients with p21-positive carcinomas (p=0.02 and p=0.005). Expression of p53 was related to a better overall survival (p=0.048). The combination of p21-negative/p53-positive expression was significantly related to better recurrence-free and overall survival (p=0.007 and p=0.0001) and gained independent prognostic significance (HR: 3.4, p=0.01). Moreover, patients with combined p21 -/p53 + expression had a remarkable benefit in overall survival after adjuvant chemotherapy as compared to the p21 -/p53 -subgroup (HR: 3.6, p=0.027). Our data suggest that the assessment of both p53 and p21 expression may provide prognostic information in colorectal cancer patients. This combination might be helpful to identify patients who could benefit from chemotherapy.

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“…40 Although histologic grades have been shown to be significantly associated with prognosis, 2,40 the ambiguity of intermediate-grade tumors 55,67 and the marked degree of interobserver variation, with as low as 50% agreement between pathologists in some studies, have led to questioning of the relevance of the current histologic grading system. 23,36,37 The propensity for uncontrolled cellular proliferation is a hallmark of cancer, 17 and as such, measures of cellular proliferation have been used extensively to prognosticate both human 14,18,19,41,46,47,63,64 and veterinary neoplastic diseases. 1,3,20,22,24,26,29,34,49,52,53,56 In veterinary medicine, the most commonly used methods to evaluate cellular proliferation include proliferating cell nuclear antigen (PCNA) and Ki67 immunostaining and argyrophilic nucleolar organizing region (Ag-NOR) histochemical staining.…”

mentioning

confidence: 99%

Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

et al. 2007

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Abstract. Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. The goals of this study were to evaluate and compare the utility of the proliferation markers Ki67, proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing region (AgNOR) as independent prognostic markers for canine MCTs and to evaluate the use of these markers in combination, as each marker assesses different aspects of cellular proliferation. An additional goal of this study was to evaluate the associations between cellular proliferation and c-KIT mutations and between cellular proliferation and aberrant KIT protein localization in canine MCTs. Fifty-six MCTs treated with surgical excision alone were included in this study. Each MCT was evaluated for Ki67 expression, PCNA expression, and KIT protein localization using immunohistochemistry; for AgNOR counts using histochemical staining; and for the presence of internal tandem duplication c-KIT mutations using polymerase chain reaction amplification. In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. On the basis of these results, we recommend that the evaluation of cellular proliferation, including evaluations of both Ki67 expression and AgNORs, should be routinely used in the prognostication of canine MCTs. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs.

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The Significance of Tumor Markers for Proliferation and Apoptosis in Predicting Survival in Colorectal Cancer

Abstract: Colon cancer and rectal cancer seem to have different biologic behavior, at least with respect to apoptosis, cytoplasmic p53 expression, and perhaps Ki-67 and carcinoembryonic antigen. Further studies are needed to clarify the significance of these factors.

Cited by 65 publications

References 43 publications

Telomere function in colorectal cancer

Telomere function in colorectal cancer

Combination of p53 expression and p21 loss has an independent prognostic impact on sporadic colorectal cancer

Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

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