Expression and clinical significance of cell cycle regulatory proteins in gallbladder and extrahepatic bile duct cancer

Wan Bae Kim, Hyung Joon Han, Hyun Joo Lee, Sung Soo Park, Tae Jin Song, Han Kyeom Kim, Sung Ock Suh, Young Chul Kim, Sang Yong Choi

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    15 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)23-34
    Number of pages12
    JournalAnnals of Surgical Oncology
    Volume16
    Issue number1
    DOIs
    Publication statusPublished - 2009 Jan

    Bibliographical note

    Funding Information:
    1Department of Surgery, Korea University Medical College Guro Hospital, 80 Guro-dong, Guro-gu, Seoul 152-703, South Korea; 2Department of Pathology, Korea University Medical college, 80 Guro-dong, Guro-gu, Seoul, South Korea; 3Korea Lung Tissue Bank Assigned and Supported by the Korea Science & Engineering Foundation by the Ministry of Science & Technology, Seoul, South Korea; 4Department of Surgery, Korea University Medical college Ansan Hospital, Gojan 1-dong, Danwon-gu, Gyeonggi-do, Ansan-si 425-707, South Korea; 5Department of Surgery, Korea University Medical College Anam Hospital, Aanm-dong 5-ga, Seongbuk-gu, Seoul 136-705, South Korea

    Funding Information:
    ACKNOWLEDGEMENTS This work was supported by a grant (no. R21-2002-000-00015-0) from the National Research Resource Bank Program of the Korea Science and Engineering Foundation by the Ministry of Science & Technology.

    ASJC Scopus subject areas

    • Surgery
    • Oncology

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