PMID- 14691914
OWN - NLM
STAT- MEDLINE
DCOM- 20040206
LR  - 20190722
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 34
IP  - 12
DP  - 2003 Dec
TI  - Major histocompatibility complex status in breast carcinogenesis and relationship 
      to apoptosis.
PG  - 1283-9
AB  - Major histocompatibility complex (MHC) molecules are of central importance in 
      regulating the immune response against tumors. In this study we used 
      immunohistochemistry to study human leukocyte antigen (HLA) class I and II 
      antigen expression in normal breast tissues and benign, preneoplastic, primary, 
      and metastatic breast lesions using antibodies against beta-2-microglobulin 
      (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and 
      benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total 
      loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, 
      in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node 
      metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 
      30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 
      metastatic case were positive for this antigen. Both HLA class I and II antigen 
      expression were more frequently down-regulated in metastatic lesions than in 
      primary breast lesions (P <0.05), and a tendency toward a simultaneous defective 
      expression of HLA class I and II antigens was observed in primary carcinomas (P = 
      0.07). However, no correlation was found between the expression of any of the 
      aforementioned molecules and pathological parameters or survival. Interestingly, 
      HLA class I expression was expressed more frequently in tissues with high 
      apoptotic activity and was significantly associated with the expression of the 
      proapoptotic bax gene (P = 0.02), and was inversely associated with expression of 
      the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA 
      class I and II antigen expression are early events in breast carcinogenesis and 
      play significant roles in metastatic progression. In addition, their expression 
      is correlated with apoptosis-regulating proteins, which may influence the 
      cytotoxicity of T cells against HLA class I-specific tumor antigens.
FAU - Redondo, Maximino
AU  - Redondo M
AD  - Department of Biochemistry, Hospital Costa del Sol, Marbella, Spain.
FAU - Garcia, Julian
AU  - Garcia J
FAU - Villar, Eduardo
AU  - Villar E
FAU - Rodrigo, Isabel
AU  - Rodrigo I
FAU - Perea-Milla, Emilio
AU  - Perea-Milla E
FAU - Serrano, Alfonso
AU  - Serrano A
FAU - Morell, Miguel
AU  - Morell M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (BAX protein, human)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis/*physiology
MH  - Breast Neoplasms/*genetics/*immunology/pathology
MH  - Cell Transformation, Neoplastic/genetics/immunology
MH  - Female
MH  - Genes, bcl-2/physiology
MH  - Histocompatibility Antigens Class I/biosynthesis
MH  - Histocompatibility Antigens Class II/biosynthesis
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis/genetics/immunology/pathology
MH  - Major Histocompatibility Complex/*physiology
MH  - Middle Aged
MH  - Neoplasm Invasiveness/genetics/immunology
MH  - Precancerous Conditions/genetics/immunology/pathology
MH  - Proto-Oncogene Proteins/metabolism
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - bcl-2-Associated X Protein
MH  - beta 2-Microglobulin/biosynthesis
EDAT- 2003/12/24 05:00
MHDA- 2004/02/10 05:00
CRDT- 2003/12/24 05:00
PHST- 2003/12/24 05:00 [pubmed]
PHST- 2004/02/10 05:00 [medline]
PHST- 2003/12/24 05:00 [entrez]
AID - S0046817703004714 [pii]
AID - 10.1016/j.humpath.2003.06.001 [doi]
PST - ppublish
SO  - Hum Pathol. 2003 Dec;34(12):1283-9. doi: 10.1016/j.humpath.2003.06.001.