title: Loss of PAR-3 protein expression is associated with invasion, lymph node metastasis, and poor survival in esophageal squamous cell carcinoma.
abstract: Disrupted cell polarity is a feature of epithelial cancers. The partitioning defective 3 (PAR-3) protein, a key component of the PAR complex that regulates the polarization of cells, is involved in tight junction formation at epithelial cell-cell contacts. Our previous study detected a homozygous deletion of the PAR-3 gene in esophageal squamous cell carcinoma (ESCC) cell lines and frequent copy number loss of the PAR-3 gene in primary ESCC. Here, we aimed to investigate the clinicopathological relevance of altered expression of the PAR-3 protein in primary ESCC. We immunohistochemically analyzed expression of the PAR-3 protein, as well as that of other tight junction proteins, ZO-1 and claudin-1, in 74 primary ESCCs. While the PAR-3 protein was expressed in the cytoplasm of basal cells, it was localized on the plasma membrane of suprabasal cells of normal squamous epithelium of the esophagus. Of the 74 ESCC tumors, 20 (27%), 11 (15%), and 13 (18%) were negative for PAR-3, ZO-1, and claudin-1 proteins, respectively. Negative PAR-3 protein expression, but not negative ZO-1 or claudin-1 expression, was significantly associated with deeper tumor invasion (P<.01), positive lymph node metastasis (P=.03), and advanced tumor stage (P=.01). Patients with PAR-3-negative tumors showed marginally significantly shorter overall survival after surgery than those with PAR-3-positive tumors (P=.053). In conclusion, these results suggest that PAR-3 protein expression is frequently lost in primary ESCC and that loss of the PAR-3 protein is associated with aggressive clinicopathological features of ESCC.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kitaichi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan. Electronic address: yasuik@koto.kpu-m.ac.jp.
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gen
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Dohi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Iwai
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tomie
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Terasaki
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Umemura
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Michihisa
authors.initials: M
authors.lastname: Moriguchi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sumida
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mitsuyoshi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Kobe, 650-0017, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell; D018797:Cell Cycle Proteins / Q000032:analysis*; D062445:Claudin-1 / Q000032:analysis; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D062826:Zonula Occludens-1 Protein / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; D018797:Cell Cycle Proteins; D062445:Claudin-1; D008565:Membrane Proteins; C509689:PARD3 protein, human; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: Claudin-1; Esophageal squamous cell carcinoma; PAR-3; Tight junction; ZO-1