Prognostic and Diagnostic Significance of β-Catenin Nuclear Immunostaining in Colorectal Cancer

Abstract

In the present study, we investigated the prognostic and diagnostic significance of ␤-catenin nuclear immunostaining in 60 specimens of normal colorectal tissue; 180 specimens of colorectal polyps, adenomas, and carcinomas; and 40 specimens from patients with the simultaneous occurrence of polyps, adenomas, and carcinomas. Additional specimens from 59 patients with colorectal carcinoma and 14 patients with adenoma who subsequently developed carcinoma were examined for possible survival study. Immunohistochemical staining showed that the occurrence of nuclear ␤-catenin correlated with the sequential stages in colorectal carcinogenesis, in which positive staining was observed in 0% of normal tissues, 8% of polyps, 92% of adenomas, and 100% of carcinomas. High immunohistochemical scores in colorectal carcinoma were significantly associated with lymph node metastasis and poor survival. Adenomas associated with synchronous or metachronous carcinomas showed significantly higher levels of nuclear ␤-catenin compared with adenomas without associated carcinomas. Nuclear translocation of ␤-catenin was rare or absent in other types of cytokeratin 20 positive adenocarcinomas examined (99 cases). Thus, it was positive in only 7% of colonic mucinous adenocarcinomas, 3% of pancreatic adenocarcinomas, 8% of ovarian mucinous cystadenocarcinomas, and 0% of gastric adenocarcinomas. However, 100% of primary and metastatic colorectal adenocarcinomas were positive for nuclear staining for ␤-catenin. Thus, nuclear staining for ␤-catenin may serve as an additional parameter to help distinguish colorectal adenocarcinomas from adenocarcinomas of other tissue sites. Collectively, the present large-scale study has clearly addressed the clinical significance of ␤-catenin nuclear translocation with respect to tumor progression, survival, and differential diagnosis.

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

“…When the Wnt/ β-catenin pathway has an abnormal signal, the epithelial cells accumulate β-catenin in the nucleus and/or cytoplasm (Morin et al 1997;Miller et al 1999;Polakis 2000). The level of β-catenin expression correlates with the stages of progression in colorectal carcinoma (Wong et al 2004), and β-catenin expression at the invasive front is a risk factor for lymph node metastasis in early carcinoma and a poor prognostic factor for disease-specific survival in advanced carcinoma (El-Bahrawy et al 2001;Utsunomiya et al 2001;Masaki et al 2003). These results suggested that β-catenin is useful for the diagnosis of tumor budding in submucosal invasive colorectal carcinoma.…”

Clinical Significance of Cytokeratin 20-Positive Circulating Tumor Cells Detected by a Refined Immunomagnetic Enrichment Assay in Colorectal Cancer Patients

“…Quantification of CK20 pCTCs as detected by this refined immunomagnetic enrichment assay has high potential for the differential diagnosis of colorectal cancer and their serial measurements may be clinically useful to monitor disease progression. Finally, the success of this refined immunomagnetic enrichment assay has opened up new possibilities in CTC detection as CTC shedding from various cancers may be further characterized after immunomagnetic enrichment with their respective specific tumor markers using immunocytochemical staining (27), in situ hybridization (28), or even molecular profiling using quantum dot technology (29,30).…”

Clinicopathological Significance of Fascin1 and Β-Catenin Expression in Colorectal Adenocarcinoma; An Immunohistochemical Study"

“…Wong [27]alsonoticed no nuclear β-catenin accumulation in normal tissues, whereas it was seen in 8% of polyps, 92% of adenomas, and 100% of carcinomas.…”

“…Thus, tumors having a large portion of Fascin1-positive cells might have a high potential for invasive manners. [27]noticed that the expression of nuclear β-catenin increased during the development of carcinoma. There is also evidence that carcinoma in situ CRCs are frequently associated with high nuclear β-catenin expression [28].…”