The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer.
BACKGROUND
MUC1 and MUC3 are from a large family of glycoproteins with an aberrant expression profile in various malignancies. Much interest has been focused on the role of these proteins in the development and progression of colorectal cancer; however, no previous studies have included the highly confounding variable of vascular invasion in their survival analysis. Using high throughput tissue microarray technology we assessed the prognostic value of MUC1 and MUC3 expression in the largest cohort of colorectal cancer patients to date. We propose that tumours lacking expression of MUC1 and MUC3 will be more likely to metastasise, due to previously observed loss of cell-cell adhesion, and this will therefore lead to more aggressive cancers with poorer prognosis.


METHODS
A tissue micro-array was prepared from tumour samples of 462 consecutive patients undergoing resection of a primary colorectal cancer. A comprehensive prospectively recorded data base with mean follow up of 75 months was collected and included common clinicopathological variables and disease specific survival. Immunohistochemical analysis of MUC1 and MUC3 expression was performed using antibodies NCL-MUC1 and 1143/B7 respectively, results were correlated with the variables within the database.


RESULTS
Positive expression of MUC1 and MUC3 was seen in 32% and 74% of tumours respectively. On univariate analysis no correlation was seen with either MUC1 or MUC3 and any of the clinicopathological variables including tumour grade and stage, vascular invasion and tumour type. Kaplan-Meier analysis demonstrated a significant reduction in disease specific survival with MUC1 positive tumours (p = 0.038), this was not seen with MUC3 (p = 0.552). On multivariate analysis, using Cox proportional hazards model, MUC1 expression was shown to be an independent marker of prognosis (HR 1.339, 95%CI 1.002-1.790, p = 0.048).


CONCLUSIONS
MUC1 expression in colorectal cancer is an independent marker of poor prognosis, even when vascular invasion is included in the analysis. These results support previous studies suggesting a role for MUC1 in colorectal cancer development possibly through its effects on cell adhesion.
Duncan
Timothy J
TJ
Academic Department of Clinical Oncology, Institute of Immunology, Infections and Immunity, University of Nottingham, City Hospital, Nottingham, UK. tim.duncan@ntlworld.com
Watson
Nicholas F S
NF
Al-Attar
Ahmad H
AH
Scholefield
John H
JH
Durrant
Lindy G
LG
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D017024:Chemotherapy, Adjuvant; D003082:Colectomy / Q000379:methods; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D055263:Mucin-3 / Q000235:genetics / Q000378:metabolism*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D016019:Survival Analysis; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D018396:Mucin-1; D055263:Mucin-3