Expression and clinical significance of cell cycle regulatory proteins in gallbladder and extrahepatic bile duct cancer.
Disruption of cell cycle controls is a pathognomonic feature of all malignant cells. Therefore, we immunohistochemically investigated the relationship between cell cycle regulatory proteins and clinicopathologic features in order to identify the biomarkers related to the outcome of patients with biliary tract cancer (BTC). A cohort of paraffin-embedded specimens were selected from 36 patients, including 18 gallbladder and 18 extrahepatic bile duct cancers, who underwent curative or palliative surgical resection at Korea University Medical Center from June 1998 to December 2004. Tissue microarrays were used to investigate the immunohistochemical staining for p21, p27, p53, cyclin D1, bcl2, and Ki-67. Univariate and multivariate survival analyses were performed to determine the prognostic significance of each protein expression. Absence of p21 expression independently predicted poor outcome in all cases. Well-differentiated tumor was found to be an independent good prognostic factor in gallbladder cancer. Absence of p21 expression and moderately to poorly differentiated tumor were found to be an independent poor prognostic factor in patients with negative for neural invasion. Absence of p21 and bcl2 were found to be an independent poor prognostic factor in patients with no lymph node metastasis. Absence of p21 expression was a significant independent poor prognostic factor in BTC, partly in patients with biologically less aggressive phenotypes. This finding suggests that determination of p21 expression in surgically resected specimens may provide prognostic information in addition to conventional pathologic findings for patients with BTC, especially those who have biologically less aggressive phenotypes.
Kim
Wan-Bae
WB
Department of Surgery, Korea University Medical College Guro Hospital, 80 Guro-dong, Guro-gu, Seoul, 152-703, South Korea.
Han
Hyung-Joon
HJ
Lee
Hyun-joo
HJ
Park
Sung-Soo
SS
Song
Tae-Jin
TJ
Kim
Han-Kyeom
HK
Suh
Sung-Ock
SO
Kim
Young-Chul
YC
Choi
Sang-Yong
SY
D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D015331:Cohort Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D007723:Korea; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27