KOC (K homology domain containing protein overexpressed in cancer)

A novel molecular marker that distinguishes between benign and malignant lesions of the pancreas

Rhonda K. Yantiss, Bruce A. Woda, Gary R. Fanger, M. Kalos, Giles F. Whalen, Hiroomi Tada, Dana Andersen, Kenneth L. Rock, Karen Dresser

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

KOC (K homology domain containing protein overexpressed in cancer) is a novel oncofetal RNA-binding protein highly expressed in pancreatic carcinomas. Recently, Corixa Corporation developed a monoclonal antibody specific for KOC that can be used with standard immunohistochemical techniques. The purposes of this study were 1) to assess KOC mRNA expression in pancreatic carcinoma, 2) to determine the pattern of KOC immunoexpression among benign, borderline, and malignant pancreatic epithelial lesions, and 3) to evaluate the utility of the KOC antibody in distinguishing between these entities. mRNA was isolated from fresh pancreatic tissues (19 carcinomas, 2 normal pancreas, 1 chronic pancreatitis) and amplified using standard RT-PCR techniques. Fifteen of 19 (79%) carcinomas overexpressed KOC mRNA relative to non-neoplastic tissue samples and expression increased progressively with tumor stage: the mean copy number of KOC mRNA transcripts was 1.5, 11.1, 31, and 28 for stage I, II, III, and IV carcinomas, respectively, compared with 0.9 and 1 for normal pancreatic tissue and chronic pancreatitis, respectively. Immunostains using the KOC antibody were performed on 50 surgical resection specimens (38 invasive adenocarcinomas, 3 intraductal papillary-mucinous neoplasms, 2 mucinous cystic neoplasms, 7 chronic pancreatitis). KOC staining was present in 37 of 38 (97%) carcinomas: the staining reaction was moderate or strong in 36 of 38 (94%) and present in >50% of the tumor cells in 35 of 38 (92%) cases. Severe dysplasia of the ductal epithelium, present in 19 foci of intraductal papillary mucinous carcinoma, mucinous cystadenocarcinoma, and grade 3 pancreatic intraepithelial neoplasia (PanIN3) showed strong or moderate staining in 15 (79%) cases, whereas foci of mild and moderate dysplasia (intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms with adenoma and/or moderate dysplasia, PanIN1, and PanIN2) were uniformly negative for this marker in 25 and 22 cases, respectively. In the normal pancreas, weak background staining of acini was present in 12 of 50 (24%) cases but was easily distinguishable from the type of staining identified in neoplastic epithelium, and benign ducts and ductules were negative in all cases. Four of 38 (11%) foci of chronic pancreatitis, present in the 7 resections performed for chronic pancreatitis as well as 31 foci of peritumoral chronic pancreatitis, showed weak staining in

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume29
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

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Pancreas
Chronic Pancreatitis
Staining and Labeling
Neoplasms
Carcinoma
Messenger RNA
Epithelium
Mucinous Cystadenocarcinoma
Mucinous Adenocarcinoma
Carcinoma, Intraductal, Noninfiltrating
RNA-Binding Proteins
Protein Domains
Antibodies
Papillary Carcinoma
Adenoma
Adenocarcinoma
Monoclonal Antibodies
Polymerase Chain Reaction

Keywords

  • 1MP3
  • CRD-BP
  • Immunohistochemistry
  • L523s
  • p62
  • Pancreatic carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

KOC (K homology domain containing protein overexpressed in cancer) : A novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. / Yantiss, Rhonda K.; Woda, Bruce A.; Fanger, Gary R.; Kalos, M.; Whalen, Giles F.; Tada, Hiroomi; Andersen, Dana; Rock, Kenneth L.; Dresser, Karen.

In: American Journal of Surgical Pathology, Vol. 29, No. 2, 02.2005, p. 188-195.

Research output: Contribution to journalArticle

Yantiss, Rhonda K. ; Woda, Bruce A. ; Fanger, Gary R. ; Kalos, M. ; Whalen, Giles F. ; Tada, Hiroomi ; Andersen, Dana ; Rock, Kenneth L. ; Dresser, Karen. / KOC (K homology domain containing protein overexpressed in cancer) : A novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. In: American Journal of Surgical Pathology. 2005 ; Vol. 29, No. 2. pp. 188-195.
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abstract = "KOC (K homology domain containing protein overexpressed in cancer) is a novel oncofetal RNA-binding protein highly expressed in pancreatic carcinomas. Recently, Corixa Corporation developed a monoclonal antibody specific for KOC that can be used with standard immunohistochemical techniques. The purposes of this study were 1) to assess KOC mRNA expression in pancreatic carcinoma, 2) to determine the pattern of KOC immunoexpression among benign, borderline, and malignant pancreatic epithelial lesions, and 3) to evaluate the utility of the KOC antibody in distinguishing between these entities. mRNA was isolated from fresh pancreatic tissues (19 carcinomas, 2 normal pancreas, 1 chronic pancreatitis) and amplified using standard RT-PCR techniques. Fifteen of 19 (79{\%}) carcinomas overexpressed KOC mRNA relative to non-neoplastic tissue samples and expression increased progressively with tumor stage: the mean copy number of KOC mRNA transcripts was 1.5, 11.1, 31, and 28 for stage I, II, III, and IV carcinomas, respectively, compared with 0.9 and 1 for normal pancreatic tissue and chronic pancreatitis, respectively. Immunostains using the KOC antibody were performed on 50 surgical resection specimens (38 invasive adenocarcinomas, 3 intraductal papillary-mucinous neoplasms, 2 mucinous cystic neoplasms, 7 chronic pancreatitis). KOC staining was present in 37 of 38 (97{\%}) carcinomas: the staining reaction was moderate or strong in 36 of 38 (94{\%}) and present in >50{\%} of the tumor cells in 35 of 38 (92{\%}) cases. Severe dysplasia of the ductal epithelium, present in 19 foci of intraductal papillary mucinous carcinoma, mucinous cystadenocarcinoma, and grade 3 pancreatic intraepithelial neoplasia (PanIN3) showed strong or moderate staining in 15 (79{\%}) cases, whereas foci of mild and moderate dysplasia (intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms with adenoma and/or moderate dysplasia, PanIN1, and PanIN2) were uniformly negative for this marker in 25 and 22 cases, respectively. In the normal pancreas, weak background staining of acini was present in 12 of 50 (24{\%}) cases but was easily distinguishable from the type of staining identified in neoplastic epithelium, and benign ducts and ductules were negative in all cases. Four of 38 (11{\%}) foci of chronic pancreatitis, present in the 7 resections performed for chronic pancreatitis as well as 31 foci of peritumoral chronic pancreatitis, showed weak staining in",
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AU - Yantiss, Rhonda K.

AU - Woda, Bruce A.

AU - Fanger, Gary R.

AU - Kalos, M.

AU - Whalen, Giles F.

AU - Tada, Hiroomi

AU - Andersen, Dana

AU - Rock, Kenneth L.

AU - Dresser, Karen

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KW - CRD-BP

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