Relevance of Ki-67 antigen expression and K- ras mutation in colorectal liver metastases

Petrowsky, Henrik; Sturm, Isrid; Graubitz, O.; Kooby, David A.; Staib-Sebler, E.; Gog, C.; Köhne, C.-H.; Hillebrand, Timo; Daniel, Peter T.; Fong, Yuman; Lorenz, Matthias

doi:10.1053/ejso.2000.1029

Cited by 83 publications

(70 citation statements)

References 48 publications

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“…This marker is associated with tumor proliferation, invasiveness, and prognosis (Cattoretti et al, 1992;Petrowsky et al, 2001). In pituitary adenomas the value of Ki-67 is controversial, in relation to the aggressive behavior (de Aguiar et al, 2010;Zhao et al, 1999), and in pituitary carcinoma appear to predict rapid disease progression (Dudziak et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenomas – Clinico-Pathological, Immunohistochemical and Ultrastructural Study

Ortíz-Plata¹,

Tena-Suck²,

Pérez-Neri³

et al. 2012

Pituitary Adenomas

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Section: Discussionmentioning

confidence: 99%

Pituitary Adenomas – Clinico-Pathological, Immunohistochemical and Ultrastructural Study

Ortíz-Plata¹,

Tena-Suck²,

Pérez-Neri³

et al. 2012

Pituitary Adenomas

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“…It is satisfactory using KL-1 monoclonal antibody to detect micrometastasis in the lungs and livers of the mice in this study. Ki-67, aproliferation-associated antigen [43][44][45][46] , is expressed in all phases of the cell cycle (G1, S, G2, and M) except for G0 [47] . It is thought to be a useful predictor of aggressive tumor behavior and an indicator of patient survival [43] .…”

Section: Discussionmentioning

confidence: 99%

“…Ki-67, aproliferation-associated antigen [43][44][45][46] , is expressed in all phases of the cell cycle (G1, S, G2, and M) except for G0 [47] . It is thought to be a useful predictor of aggressive tumor behavior and an indicator of patient survival [43] . Mib-1 is raised against recombinant parts of the Ki-67 antigen [48][49][50][51][52] .…”

Section: Discussionmentioning

confidence: 99%

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

Cui

Krueger²,

Henne‐Bruns³

et al. 2001

WJG

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AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis. METHODS Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were i n v e s t i g a t e d b y i m m u n o s t a i n i n g w i t h biotinylated mab KL-1 and by RT-PCR using CK20 specific primers. RESULTS There were totally 9 of 16 surgical s p e c i m e n s g r o w i n g i n n u d e m i c e subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tu m o r . I n t h e g r o u p o f f r e s h t u m o r tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically transplanted tumors resemble the original tumor morphologically and biologically, including T A A e x p r e s s i o n s u c h a s C E A b y immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR. CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new d i a g n o s t i c m e t h o d s a n d t h e r a p e u t i c s t r a t e g i e s f o r m e t a s t a s e s i n c l u d i n g micrometastases.

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“…High proliferation (Ki-67 50%) was proved to be reliable and reproducible index. CRC patients with lesions with higher Ki-67 expression had significantly decreased survival than their counterparts, with lesions expressing lower levels of Ki-67 [29] .…”

Section: Introductionmentioning

confidence: 94%

The Interplay between p53 and p21 Tumor Suppressor Proteins in the Transformation of Colorectal Adenoma to Carcinoma

Abdulamir¹,

Hafidh²,

Mahdi³

et al. 2008

American J. of Immunology

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This study was carried out for evaluating the interplay of p53, p21 and Ki-67 proteins along the colorectal adenoma-carcinoma oncogenic transformation sequel. Therefore, Fifty colorectal cancer and 14 adenoma patients were involved. The histopathological expression of p53, p21 and Ki-67 proteins was evaluated by immunohistochemistry assay. The results revealed that remarkable overexpression of p53 protein was seen in the tumorous sections of cancer patients more than that in adenoma patients (p<0.05), while no p53 overexpression was found in the corresponding nontumorous sections. The positive expression of p21 protein was lower in the tumorous sections of cancer patients than that of adenoma patients (p<0.05) and was higher in the non-tumorous than the corresponding tumorous sections of both CRC and adenoma patients (p<0.05). The expression of p53 and p21 proteins in cancer patients was inversely correlated to each other (p<0.05) and the expression of p21 rather than p53 protein was associated with colorectal cancer staging and grading (p<0.05). Ki-67 was higher in cancer than in adenoma patients and higher in the tumorous tissue sections than the corresponding non-tumorous sections (p<0.05). The overexpression of p53 and downexpression of p21 proteins in colorectal cancer might be responsible largely for triggering the transformational changes in normal mucosa to develop adenoma and trigger also the malignant cascade from adenoma to carcinoma. P53 overexpression was shown to occur due to the mutated dysfunctional p53 gene product which loses its transcriptional activator necessary for p21 expression. The level of p21 protein which is a quantitatively affected by the loss of p53 activation is responsible for the association with cancer staging and grading that serves as a good indicator for the disease progression.

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Relevance of Ki-67 antigen expression and K- ras mutation in colorectal liver metastases

Cited by 83 publications

References 48 publications

Pituitary Adenomas – Clinico-Pathological, Immunohistochemical and Ultrastructural Study

Pituitary Adenomas – Clinico-Pathological, Immunohistochemical and Ultrastructural Study

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

The Interplay between p53 and p21 Tumor Suppressor Proteins in the Transformation of Colorectal Adenoma to Carcinoma

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