Immunohistochemical detection of mutant p53 protein in regional lymph nodes is associated with adverse outcome in stage II colorectal cancer.
Epidemiologic data identifies a cohort of Duke's B (CRC) patients whose survival more closely matches that of Duke's C. Lymph node micrometastases may account for this discrepancy. Lymph node expression of mutant p53 protein (Mp53P) has been linked to a reduction in survival in Japanese Duke's B patients. We aimed to determine the significance of nodal p53 expression in European Duke's B patients using immunohistochemistry. The study comprised 134 consecutive patients who had resections for CRC between 1984 and 1991. End points were 5 year disease free survival or CRC related death. Thirty-four subjects did not achieve end points and were excluded. We examined tumour and nodal sections for Mp53P by immunohistochemistry and correlated this with survival using a Kaplan-Meier (KM) and a Cox Proportional hazards model (CPHT). Five year survival was 73%. Fifty-eight percent of primary tumours expressed Mp53P. Tumour p53 expression did modulate survival behavior. Twenty-six percent of subjects' lymph nodes expressed Mp53P. Fifty-three per cent of those with positive and 17% of those with negative lymph nodes died of recurrence. The relative risk for nodal Mp53P expression was 3.1. There was a significant univariate relationship between lymph node p53 expression and mortality. (Log Rank p = 0.028). Multivariate analysis also showed a significant relationship with mortality. (CPHT p = .03). We conclude that lymph node expression of Mp53P is associated with increased mortality in Duke's B CRC.
Clarke
G
G
Department of Gastroenterology, Mater Misericordiae Hospital, Dublin, Ireland. gclarke@rics.bwh.harvard.edu
Ryan
E
E
Crowe
J
J
O'Keane
J C
JC
MacMathúna
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics*
D016159:Tumor Suppressor Protein p53