Article

KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas.

Department of Pathology, UMass Memorial Health Care, Worcester, MA 01655, USA.
American Journal of Surgical Pathology (Impact Factor: 4.59). 02/2005; 29(2):188-95.
Source: PubMed

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 <10% of the ductules. We conclude that KOC is a sensitive and specific marker for carcinomas and high-grade dysplastic lesions of the pancreatic ductal epithelium. Therefore, immunostains directed against KOC may be of diagnostic utility in the evaluation of pancreatic lesions, particularly when biopsy material is limited.

0 Followers
 · 
104 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMP3, a member of insulin-like growth factor II m RNA binding protein family, seems to be promising in the diagnosis of carcinomas of many organs as well as malignant melanomas and some sarcomas. It is postulated that it might be a marker of malignancy. The results of the few prior studies indicate that IMP3 has the potential to be useful in distinguishing benign and malignant tumors of thyroid. We aimed to evaluate the immunohistochemical expression of IMP3 in non-neoplastic nodules and benign and malignant tumors of the thyroid. Diagnostic accuracy study. Overall, 92 thyroid lesions, including 22 nodular hyperplasia (NH), 14 follicular adenoma (FA), 9 follicular carcinoma (FC), 37 papillary carcinoma (PC) (15 follicular variant), 3 well differentiated carcinoma-not otherwise specified (WDC-NOS), 4 poorly differentiated carcinoma (PDC) and anaplastic carcinoma (AC) were included. Immunohistochemically, cytoplasmic expression of IMP3 was evaluated in terms of extent and intensity of the staining semi-quantitatively and an immunohistochemical score (IHS) was obtained for each case. A score higher than 2 was considered positive staining. In contrast with previous studies, we observed positive staining in benign lesions, especially in benign tumors. For identifying malignant tumors, the sensitivity of IMP3 was 82.1%, specificity was 33.3%, positive predictive value (PPV) was 65.7% and negative predictive value (NPV) was 54.5%. In distinguishing neoplastic and hyperplastic lesions, the sensitivity was 50%, specificity was 15.7%, PPV was 15.7% and NPV was 50%. The IMP3 expression was similar for FA and well differentiated carcinomas (p=0.434), but there was a significant difference between hyperplastic nodules and FA (p=0.011). Our data suggest that IMP3 is effective in discriminating hyperplastic and neoplastic lesions but not useful in differentiating benign tumors from malignant tumors.
    Balkan Journal of Medical Genetics 02/2015; 32(1):30-7. DOI:10.5152/balkanmedj.2015.15547 · 0.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin-like growth factor-II mRNA-binding protein-3 (IMP3) is an important factor in carcinogenesis, although its clinical significance in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study investigated the associations between IMP3 expression and the clinicopathological parameters. IMP3 expression was assessed in 191 resected ESCC specimens, and the associations between IMP3 expression in ESCC, the clinicopathological parameters and patient prognosis were examined. Using immunohistochemistry, 113 (59.2%) tumors were identified as IMP3-positive. IMP3 positivity correlated significantly with high pathological (p)Stage, pT stage and pN stage. The IMP3-positive patients exhibited a poorer prognosis compared with the IMP3-negative patients. In univariate analyses, histology [hazard ratio (HR), 1.94; 95% confidence interval (CI), 1.18-3.49; P=0.0082], pT (HR, 2.34; 95% CI, 1.55-3.62; P<0.0001), pN (HR, 2.85; 95% CI, 1.81-4.69; P<0.0001), lymphatic invasion (HR, 2.08; 95% CI, 1.26-3.70; P=0.0036), venous invasion (HR, 1.79; 95% CI, 1.21-2.64; P=0.0039), neoadjuvant chemotherapy (NAC) (HR, 2.01; 95% CI, 1.35-3.00; P=0.0005) and IMP3 expression (HR, 2.12; 95% CI, 1.40-3.29; P=0.0003) were significantly associated with overall survival. Using multivariate analyses, histology (HR, 1.87; 95% CI, 1.13-3.29; P=0.014), pN (HR, 2.19; 95% CI, 1.36-3.66; P=0.0010), NAC (HR, 1.88; 95% CI, 1.24-2.86; P=0.0028) and IMP3 expression (HR, 1.84; 95% CI, 1.18-2.93; P=0.0064) were significant prognostic factors. IMP3 may therefore be a prognostic factor for patients with ESCC who have undergone a curative resection.
    Oncology letters 11/2014; 8(5):2027-2031. DOI:10.3892/ol.2014.2465 · 0.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that IGF2BP3 promoted the invasiveness and metastasis of pancreatic cancers through locally translated IGF2BP3-bound transcripts. In neural cells, transcripts sorted into cytoplasmic RNA granules are transported to dendrites and translated in these dendrites, thereby mediating long-term synaptic plasticity; however, such cytoplasmic RNA granules are not known to contribute to the progression of pancreatic cancer. We show evidence that IGF2BP3 and IGF2BP3-bound transcripts are localized in cytoplasmic RNA granules that accumulate in membrane protrusions of pancreatic cancer cells. Specific IGF2BP3-bound transcripts-ARF6 and ARHGEF4-that are preferentially translated in membrane protrusions induce further formation of membrane protrusions; consequently, IGF2BP3 promotes cell invasiveness and tumor metastasis. Our results provide insight into the link between regulation of localized translation in cell protrusions and the invasiveness and metastasis of pancreatic cancers. New therapies that prevent local translation in cell protrusions may hold significant clinical promise.
    Oncotarget 08/2014; 5(16):6832-6845. · 6.63 Impact Factor