Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression Is associated with vessel invasion and shortened survival.
Mucins play pivotal roles in influencing cancer biology, for example affecting carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to investigate the significance of expression profiles of two mucins in particular, MUC1 and MUC2, their correlations with various clinicopathological features, and prognosis in gallbladder adenocarcinoma (GBAC). We performed immunohistochemistry from patients with surgically resected GBAC, using antibodies against mucin core proteins MUC1/DF3 and MUC2/Ccp58 in 81 paraffin-embedded tumor samples. MUC1 or MUC2 expression was considered to be high when ≥ 20% or 10% of the GBAC cells showed positive staining, respectively. High MUC1 expression was revealed to have a significant relationship to the presence of pathologically lymphatic and vascular invasion, and regional lymph node metastasis. By contrast, high MUC2 expression showed a significant correlation with pathologically perineural invasion, T stage ≥ 3, and post-operative recurrence. Moreover, MUC1 showed significantly positive co-expression and potentially complementary correlations with MUC2. Multivariate analyses demonstrated that the high MUC1 expression group had significantly shorter disease-specific survival times. However, the combination of both high MUC1 and MUC2 expression did not predict worse outcome in GBACs. Therefore, although each mucin has a somewhat important role in the pathogenesis of GBAC progression, MUC1 can independently predict vessel invasion and poor prognosis in patients with GBAC. The detection of MUC1 might well offer a useful parameter for providing clinical management and treatment against postsurgical GBACs.
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Tsubasa
T
Hiraki
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. sohsuke@m.kufm.kagoshima-u.ac.jp.
Sohsuke
S
Yamada
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Michiyo
M
Higashi
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Kazuhito
K
Hatanaka
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Seiya
S
Yokoyama
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Ikumi
I
Kitazono
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Yuko
Y
Goto
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Mari
M
Kirishima
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.|Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Surinder K
SK
Batra
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Suguru
S
Yonezawa
Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Akihide
A
Tanimoto
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D005706:Gallbladder Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis / Q000096:biosynthesis*; D055262:Mucin-2 / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; C524625:MUC2 protein, human; D018396:Mucin-1; D055262:Mucin-2