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Assessment of biomarkers in paired primary and recurrent colorectal adenocarcinomas

Authors
 Jinsil Seong  ;  Eun Ji Chung  ;  Hogeun Kim  ;  Gwi Eon Kim  ;  Nam Kyu Kim  ;  Seung Kuk Sohn  ;  Jin Sik Min  ;  Chang Ok Suh 
Citation
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, Vol.45(5) : 1167-1173, 1999 
Journal Title
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 
ISSN
 0360-3016 
Issue Date
1999
MeSH
Adult ; Aged ; Apoptosis*/genetics ; Biomarkers, Tumor/analysis* ; CDC2 Protein Kinase/analysis ; Cell Division ; Colonic Neoplasms/chemistry* ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/pathology ; Cyclin B/analysis ; Cyclin B1 ; Cyclin D1/analysis ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/analysis ; DNA Fragmentation ; Female ; Humans ; In Situ Nick-End Labeling ; Male ; Middle Aged ; Neoplasm Recurrence, Local/chemistry* ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; Proliferating Cell Nuclear Antigen/analysis ; Rectal Neoplasms/chemistry* ; Rectal Neoplasms/drug therapy ; Rectal Neoplasms/pathology ; Sigmoid Neoplasms/chemistry ; Sigmoid Neoplasms/drug therapy ; Sigmoid Neoplasms/pathology ; Tumor Suppressor Protein p53/analysis
Abstract
PURPOSE: Recurrent colorectal cancers respond poorly to anticancer treatment including radiotherapy. To better understand the biological characteristics of the recurrent colorectal tumor, we investigated various biomarkers regulating cell proliferation and cell loss in paired primary and recurrent colorectal tumor specimens within each individual. METHODS AND MATERIALS: From a total of 11 colorectal adenocarcinoma patients, 22 specimens of paired primary and recurrent tumors were obtained for analysis. Apoptosis was evaluated by TUNEL labeling of apoptotic DNA fragmentation. Other biomarkers including proliferating cell nuclear antigen (PCNA), p53, WAF1, p34cdc2, and cyclins B1 and D1 were analyzed by immunohistochemical stains. RESULTS: PCNA index (PCNAI) showed an increase in 6 and a decrease in 5 recurrent tumors compared to primary tumors. Median PCNAI in primary and recurrent tumors were 33.5 and 48.3, respectively (p = 0.16). In contrast, the apoptotic index (AI) decreased in 9 of 11 recurrent tumors compared to primary tumors. Median AI decreased from 4.3 in primary tumors to 1.4 in recurrent tumors (p = 0.04). The p53 expression increased in more than half of recurrent tumors compared to primary tumors. Mean staining score increased from 0.7 in primary tumors to 1.2 in recurrent tumors (p = 0.059). WAF1 and cyclin B1 did not show significant change. In contrast, both cyclin D1 and p34cdc2 increased significantly in recurrent tumors. These two biomarkers showed increased expression in 8 (cyclin D1) and 7 (p34cdc2) recurrent tumors, respectively, compared to their primary counterparts. Mean staining scores of both biomarkers in recurrent tumors increased by more than twofold compared to those in primary tumors and these differences were statistically significant (cyclin D1, p = 0.007; p34cdc2, p = 0.008). CONCLUSION: This study showed significantly decreased apoptosis in recurrent colorectal tumors compared to their primary counterparts. The underlying regulatory mechanisms included increased expression of p53 and altered cell cycle regulators such as increased cyclin D1 and p34cdc2. With further study, it may be used for developing a new therapeutic strategy for the treatment of recurrent colorectal cancer.
Full Text
https://www.sciencedirect.com/science/article/pii/S0360301699003028
DOI
10.1016/s0360-3016(99)00302-8
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173775
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