Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?
OBJECTIVE
To characterize HLA class I antigen expression in non-small cell lung cancer (NSCLC) lesions, and to assess the clinical significance of these molecules' downregulation.


METHODS
One hundred and ninety primary formalin fixed, paraffin embedded NSCLC lesions were stained with HLA class I heavy chain-specific mAb HC-10. Results were scored as percentage of stained tumor cells and categorized into three groups: 0-24% (negative), 25-75% (heterogeneous) and >75% (positive). HLA class I antigen expression was correlated with clinical and pathologic predictors of time to progression and survival and analyzed using the chi-square test. Association between HLA class I antigen expression and survival was assessed using Cox regression models, while controlling for confounders.


RESULTS
HLA class I antigen expression was negative, heterogeneous and positive in 153, 25 and 12 primary NSCLC lesions, respectively. Independent variables significantly associated with survival included tumor stage, PS and weight loss. The median survival times were 40.6, 44.0 and 17.9 months for patients with a HLA class I antigen expression scored as negative, heterogeneous and positive, respectively.


CONCLUSIONS
HLA class I antigen defects were found with high frequency (93.6%) in NSCLC lesions. HLA class I antigen downregulation was associated with improved survival, although this association was not statistically significant. These results, which parallel similar findings in uveal melanoma and in breast carcinoma, raise the possibility that NK cells may play a role in the control of NSCLC tumors.
Ramnath
N
N
Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Nithya.ramnath@roswellpark.org
Tan
D
D
Li
Q
Q
Hylander
B L
BL
Bogner
P
P
Ryes
L
L
Ferrone
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism* / Q000401:mortality*; D015536:Down-Regulation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I