Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: results from IALT, JBR.10 and ANITA.
BACKGROUND
CALGB 9633 was a randomized trial of observation versus adjuvant chemotherapy for patients with stage IB non-small cell lung cancer (NSCLC). In CALGB 9633, the presence of mucin in the primary tumor was associated with shorter disease-free survival (DFS; hazard ratio (HR) = 1.9, p = 0.002) and overall survival (OS; HR = 1.9, p = 0.004).


METHODS
To validate these results, mucin staining was performed on primary tumor specimens from 780 patients treated on IALT, 351 on JBR.10 and 150 on ANITA. The histochemical technique using mucicarmine was performed. The prognostic value of mucin for DFS and OS was tested in a Cox model stratified by trial and adjusted for clinical and pathological factors. A pooled analysis of all 4 trials was performed for the predictive value of mucin for benefit from adjuvant chemotherapy.


RESULTS
The cross-validation group had 48% squamous, 37% adenocarcinoma and 15% other NSCLC compared with 29%, 56%, and 15%, respectively in CALGB. Among 1262 patients with assessable results, mucin was positive in IALT 24%, JBR.10 30%, ANITA 22% compared with 45% in CALGB. Histology was the only significant covariate (p < 0.0001) in multivariate analysis with mucin seen more commonly in adenocarcinoma (56%) compared with squamous (5%) and other NSCLC (15%). Mucin was a borderline negative prognostic factor for DFS (HR = 1.2 [1.0-1.5], p = 0.06) but not significantly so for OS (HR=1.1 [0.9-1.4], p = 0.25). Prognostic value did not vary according to histology: HR = 1.3 [1.0-1.6] in adenocarcinoma vs. 1.6 [1.2-2.2] for DFS in other histology (interaction p = 0.69). Mucin status was not predictive for benefit from adjuvant chemotherapy (test of interaction: DFS p = 0.27; OS p = 0.49).


CONCLUSIONS
Mucin was less frequent in the cross-validation group due to its higher percentage of squamous cell carcinomas. The negative impact of mucin was confirmed for DFS but not for OS. Mucin expression was not predictive of overall survival benefit from adjuvant chemotherapy.
Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA(2). Electronic address: grazians@upstate.edu.
Stephen L
SL
Graziano
Benjamin
B
Lacas
Robin
R
Vollmer
Robert
R
Kratzke
Helmut
H
Popper
Martin
M
Filipits
Lesley
L
Seymour
Frances A
FA
Shepherd
Rafael
R
Rosell
Anne Sophie
AS
Veillard
Miquel
M
Taron
Jean-Pierre
JP
Pignon
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism*; D015999:Multivariate Analysis; D011013:Pneumonectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
D009077:Mucins
Adenocarcinoma; Mucin; Non-small cell lung cancer; Predictive factors; Prognostic factors