Prognostic value of humbug gene overexpression in stage II colon cancer.

Full Abstract

Overexpression of aspartyl (asparaginyl) beta-hydroxylase (AAH) has been demonstrated in hepatocellular carcinoma, cholangiocarcinoma, and pancreatic carcinoma. AAH has an important role in regulating cell motility and invasiveness. Humbug is a truncated homolog of AAH, with a role in calcium regulation. The present study examines the prognostic use of AAH and humbug gene expression in stage II colon cancer. One hundred thirty cases of TNM stage II colon carcinoma were retrieved from the Rhode Island Hospital pathology archives. Tissue microarrays were immunostained with the FB50 and 15C7 monoclonal antibodies generated to recombinant AAH. However, FB50 also recognizes humbug. In addition, AAH and humbug expression was analyzed in samples of colon cancer and adjacent normal mucosa by real-time quantitative reverse transcriptase-polymerase chain reaction. Humbug (FB50) expression was localized to the tumor cytoplasm, whereas normal colonic epithelium did not exhibit significant immunoreactivity. Humbug staining was detected in 85% of the neoplasms, 23% of which stained strongly. Strong humbug immunoreactivity positively correlated with nuclear grade (P = .006) and inversely with survival (P = .027). In contrast to humbug, AAH (15C7) immunoreactivity was seen in normal and neoplastic epithelium. There was no correlation between AAH immunoreactivity and tumor grade, or survival. Correspondingly, reverse transcriptase-polymerase chain reaction studies demonstrated up-regulation of humbug but not AAH in 95% of colon carcinomas relative to adjacent colon cancer-free mucosa (P < .0001). This study demonstrates that high levels of humbug immunoreactivity in colon carcinomas correlate with histologic grade and tumor behavior, suggesting that humbug can serve as a prognostic biomarker of TNM stage II colon cancers. In addition, molecular studies demonstrated that the increased levels of FB50 detected were due to humbug, as opposed to AAH overexpression.

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Author information

Author/s: Wang, JiYi (J); de la Monte, Suzanne M (SM); Sabo, Edmond (E); Kethu, Sripathi (S); Tavares, Rosemarie (R); Branda, Mark (M); Simao, Lelia (L); Wands, Jack R (JR); Resnick, Murray B (MB);

Affiliation: Department of Pathology, Liver Research Center, Rhode Island Hospital, Brown Medical School, Providence, RI 02903, USA.

Grants: 5 P20 RR017695-02 (Agency:NCRR NIH HHS) ; AA-02169 (Agency:NIAAA NIH HHS) ; AA-02666 (Agency:NIAAA NIH HHS) ; AA-11431 (Agency:NIAAA NIH HHS) ; AA-12908 (Agency:NIAAA NIH HHS) ; CA-35711 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Human pathology (Hum Pathol), published in United States. (Language: eng)

Reference: 2007-Jan; vol 38 (issue 1) : pp 17-25

Dates: Created 2006/12/15; Completed 2007/02/15; Revised 2007/12/03;

PMID: 17020779, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal - analysis; immunology
Antibody Specificity - immunology
Colonic Neoplasms - enzymology; genetics; pathology
Female
Gene Expression Regulation, Enzymologic - genetics
Gene Expression Regulation, Neoplastic - genetics
Humans

Immunohistochemistry
Isoenzymes - genetics; immunology; metabolism
Kaplan-Meiers Estimate
Male
Middle Aged
Mixed Function Oxygenases - genetics; immunology; metabolism
Neoplasm Staging
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis

Associated Chemicals: Antibodies, Monoclonal (0) ; Isoenzymes (0) ; Mixed Function Oxygenases (EC 1.-) ; aspartic acid 2-oxoglutarate-dependent dioxygenase (EC 1.14.11.-)

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