PMID- 12480922
OWN - NLM
STAT- MEDLINE
DCOM- 20030110
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 82
IP  - 12
DP  - 2002 Dec
TI  - Down-regulation of HLA-A expression correlates with a better prognosis in 
      colorectal cancer patients.
PG  - 1725-33
AB  - To evaluate the prognostic impact of human leukocyte antigen class I (HLA-I) 
      expression on immune surveillance in colorectal cancer, we studied 88 curatively 
      resected tumors for HLA-A and HLA-B/C expression and correlated these data to 
      clinical and histopathological parameters. HLA-A was normal (all tumor cells had 
      HLA expression) in 32%, reduced (HLA-negative and -positive tumor cells 
      coexisted) in 56%, or absent (no tumor cells expressed HLA) in 12% of evaluable 
      cases. HLA-B/C was normal in 47%, reduced in 47%, and absent in 7% of the cases. 
      Considering both markers, total HLA-I expression was normal in 27%, reduced in 
      63%, absent in 7%, and could not be evaluated in 3% of the cases due to absent 
      HLA-A expression in tumor and normal cells. Down-regulation of HLA-A expression 
      significantly correlated with a lower tumor stage (p = 0.005), mucinous tumors (p 
      = 0.05), a lower incidence of recurrences (p = 0.03), and a longer disease-free 
      survival (p = 0.02). Down-regulation of HLA-B/C expression correlated with a 
      lower tumor stage (p < 0.001) and a longer disease-free survival (p = 0.04). In 
      multivariate analysis, HLA-A down-regulation was the only prognostic factor 
      correlated with a longer disease-free survival (p = 0.02). Six tumors were 
      negative for HLA-A and -B/C and did not recur during follow-up. Therefore, we 
      analyzed microsatellite instability (MSI) in these cases. Three of these six 
      tumors indeed showed down-regulation of MLH-1, MSH-2, or MSH-6, indicating a 
      MSI-high phenotype. Beta-2-microglobulin protein expression was lost in five of 
      six of the HLA-I-negative cases, but frame shift mutations in three repetitive 
      sequences in beta2-microglobulin were absent. In contrast, loss of MLH-1, MSH-2, 
      and MSH-6-protein expression was only observed in two of nine matched controls 
      with reduced or normal HLA-A and -B/C expression. Our data showed that HLA-I was 
      down-regulated in 72% of colorectal cancers and provided independent prognostic 
      information for a longer disease-free survival. The better prognosis may be 
      caused by elimination of HLA-negative cells by natural killer cells or by an 
      attenuated tumor aggressiveness, as is seen in tumors with a MSI-high phenotype.
FAU - Menon, Anand G
AU  - Menon AG
AD  - Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
FAU - Morreau, Hans
AU  - Morreau H
FAU - Tollenaar, Rob A E M
AU  - Tollenaar RA
FAU - Alphenaar, E
AU  - Alphenaar E
FAU - Van Puijenbroek, Marjo
AU  - Van Puijenbroek M
FAU - Putter, Hein
AU  - Putter H
FAU - Janssen-Van Rhijn, Connie M
AU  - Janssen-Van Rhijn CM
FAU - Van De Velde, Cornelis J H
AU  - Van De Velde CJ
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
FAU - Kuppen, Peter J K
AU  - Kuppen PJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
SB  - IM
MH  - Adenocarcinoma/*metabolism/pathology/surgery
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor
MH  - Colorectal Neoplasms/*metabolism/pathology/surgery
MH  - DNA, Neoplasm/analysis
MH  - Disease-Free Survival
MH  - Down-Regulation
MH  - Female
MH  - HLA-A Antigens/*biosynthesis/genetics
MH  - HLA-B Antigens/biosynthesis/genetics
MH  - HLA-C Antigens/biosynthesis/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Neoplasm Staging
MH  - Repetitive Sequences, Nucleic Acid/genetics
EDAT- 2002/12/14 04:00
MHDA- 2003/01/11 04:00
CRDT- 2002/12/14 04:00
PHST- 2002/12/14 04:00 [pubmed]
PHST- 2003/01/11 04:00 [medline]
PHST- 2002/12/14 04:00 [entrez]
AID - S0023-6837(22)03615-7 [pii]
AID - 10.1097/01.lab.0000043124.75633.ed [doi]
PST - ppublish
SO  - Lab Invest. 2002 Dec;82(12):1725-33. doi: 10.1097/01.lab.0000043124.75633.ed.