Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival.
OBJECTIVE
Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb.


METHODS
Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen.


RESULTS
HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival.


CONCLUSIONS
The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.
Graus
F
F
Service of Neurology, Hospital Clínic i Provincial, Barcelona, Spain. graus@medicine.ub.es
Dalmou
J
J
Reñé
R
R
Tora
M
M
Malats
N
N
Verschuuren
J J
JJ
Cardenal
F
F
Viñolas
N
N
Garcia del Muro
J
J
Vadell
C
C
Mason
W P
WP
Rosell
R
R
Posner
J B
JB
Real
F X
FX
D000912:Antibodies, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D018288:Carcinoma, Small Cell / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D002493:Central Nervous System Diseases / Q000276:immunology; D051959:ELAV Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D016601:RNA-Binding Proteins / Q000276:immunology*; D012044:Regression Analysis; D015996:Survival Rate; D016896:Treatment Outcome
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D051959:ELAV Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins