Abstract
To investigate alpha catenin expression in surgically resected human colorectal cancers to evaluate its prognostic value during long term follow up. Immunohistochemistry was used to compare the expression of alpha catenin with conventional prognostic factors in 187 colorectal cancer patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the intensity of expression of alpha catenin and its distribution in cancer cells is correlated with survival was tested with the long-rank test, hazard ratios, and their confidence intervals. Uniform membranous alpha catenin staining localised to the intercellular borders was observed in 46% of the tumours; 55% of all tumours had either heterogeneous or negative alpha catenin expression, and staining intensity was either negative or weak in 42% of the tumours. The cancer related and recurrence-free survival rates were lower among patients with a weak alpha catenin intensity in tumour epithelium (p < 0.001), a low fraction of positive tumour cells (p < 0.001), and an additional cytoplasmic accumulation of alpha catenin (p < 0.001). In multivariate analysis, the intensity of alpha catenin expression in tumour epithelium predicted cancer related survival independently; alpha catenin localisation in tumour epithelium was an independent prognostic factor of recurrence-free survival in the group as a whole and in the T1-3N0M0 tumour subgroup. A low proportion of positive carcinoma cells, additional cytoplasmic accumulation of alpha catenin, and reduced expression intensity in tumour epithelium predict a poor survival rate. The results suggest that alpha catenin has prognostic significance in colorectal cancer.
MeSH Terms
Adult
Aged
Aged, 80 and over
Analysis of Variance
Biomarkers, Tumor/metabolism
Cadherins/metabolism
Colorectal Neoplasms/metabolism,surgery
Cytoskeletal Proteins/metabolism
Disease-Free Survival
Female
Follow-Up Studies
Humans
Immunoenzyme Techniques
Male
Middle Aged
Neoplasm Proteins/metabolism
Prognosis
Survival Rate
Treatment Outcome
alpha Catenin
Chemicals
Biomarkers, Tumor
CTNNA1 protein, human
Cadherins
Cytoskeletal Proteins
Neoplasm Proteins
alpha Catenin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ropponen K M
Department of Pathology and Forensic Medicine, Kuopio University Hospital, University of Kuopio, Finland.
Eskelinen M J
Lipponen P K
Alhava E M
Kosma V M
References (22)
22 references, click to expand
-
Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps.
Am J Pathol. 1997 Jun;150(6):1977-84
PMID: 9176391
-
Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors.
Cancer Res. 1996 Sep 15;56(18):4154-8
PMID: 8797585
-
Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer.
Virchows Arch. 1994;424(4):375-81
PMID: 8205352
-
Tumour recurrence is associated with Jass grouping but not with differences in E-cadherin expression in moderately differentiated Dukes' B colorectal cancers.
J Clin Pathol. 1997 Mar;50(3):218-22
PMID: 9155672
-
Expression of E-cadherin, alpha-catenin, beta-catenin and plakoglobin in esophageal carcinomas and its prognostic significance: immunohistochemical analysis of 96 lesions.
Oncology. 1997 Mar-Apr;54(2):158-65
PMID: 9075789
-
E-cadherin and its associated protein catenins, cancer invasion and metastasis.
Br J Surg. 1996 Apr;83(4):437-46
PMID: 8665230
-
Role of the E-cadherin/alpha-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells.
Ann Surg Oncol. 1995 Sep;2(5):378-85
PMID: 7496831
-
Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer.
Int J Cancer. 1997 Aug 22;74(4):374-7
PMID: 9291424
-
Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin.
Histopathology. 1996 Aug;29(2):139-46
PMID: 8872147
-
Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma.
Int J Cancer. 1997 Oct 21;74(5):523-8
PMID: 9355975
-
Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis.
J Pathol. 1997 Jul;182(3):331-8
PMID: 9349237
-
Colon cancer: a review of the epidemiology.
Epidemiol Rev. 1993;15(2):499-545
PMID: 8174669
-
Statistical aspects of the analysis of data from retrospective studies of disease.
J Natl Cancer Inst. 1959 Apr;22(4):719-48
PMID: 13655060
-
Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells.
J Cell Biol. 1991 Jul;114(2):319-27
PMID: 1649199
-
Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer.
J Pathol. 1997 Jul;182(3):318-24
PMID: 9349235
-
Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer.
Cancer Res. 1992 Sep 15;52(18):5104-9
PMID: 1516067
-
Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer.
Virchows Arch A Pathol Anat Histopathol. 1992;421(2):149-56
PMID: 1514246
-
E-cadherin and alpha-catenin expression in human esophageal cancer.
Cancer Res. 1994 Jan 1;54(1):291-6
PMID: 8261454
-
Patterns of alpha- and beta-catenin and E-cadherin expression in colorectal adenomas and carcinomas.
J Pathol. 1997 Jul;182(3):325-30
PMID: 9349236
-
APC expression in normal human tissues.
J Pathol. 1997 Apr;181(4):426-33
PMID: 9196441
-
The interactions of APC, E-cadherin and beta-catenin in tumour development and progression.
J Pathol. 1997 Jun;182(2):128-37
PMID: 9274521
-
Reduced alpha-catenin and E-cadherin expression in breast cancer.
Lab Invest. 1995 May;72(5):506-12
PMID: 7745946