Table 2. Studies investigating presence and/or expression of RNA and tumour-related proteins in sputum.

Study	Cases	Controls	Method	Protein/gene	Results cases	Results controls	Se (%)	Sp (%)	Positive cytology	Remarks
Sun et al (2009)	All	Benign pulmonary disease	RTQ–PCR, immunocytochemistry	APRILa	58/71 (82%)	2/62 (3%)	82	97	Cases 10/71 (14%): all SCC Immunocytol: 11/71 (16%)	Healthy subjects: 1/65 (2%). Cutoff value: mean±2 s.d. of mRNA expression in healthy subjects
Mecklenburg et al (2004)b	All	Benign pulmonary disease	RT–PCR	MAGE-1	2/14 (14%)	0/2 (0%)	14	100	cases 1/8 (13%)	Positive cytology sample was not tested with RT–PCR. Cytology of remaining samples not performed
				MAGE-2	1/14 (7%)	0/2 (0%)	7	100
				MAGE-3/6	0/14 (0%)	0/2 (0%)	0	100
				MAGE-4	2/14 (14%)	0/2 (0%)	14	100
				MAGE-12	2/14 (14%)	0/2 (0%)	14	100
				All combined	5/14 (36%)	0/2 (0%)	36	100
Jheon et al (2004)b	All	Benign pulmonary disease	RT–N-PCR	MAGE A1–6	72/134 (54%)	3/140 (2%)	54	98	Cases 6/31 (19%)	Also spontaneous sputum collected. Data of lung cancer patients from group I (collection at the day of thoracotomy) and II (lung cancer in clinical workup) combined. Follow-up (1 year): no cancer in controls
			TRAP method	Telomerase	8/27 (30%)		30
Pasrija et al (2007)b	All	Cancer-free subjects	TRAP method	Telomerase	23/34 (68%)	3/30 (10%)	68	90
Pio et al (2010)b	All	Cancer-free subjects	Anti-factor H antibodies	Complement factor Ha			80	88		Also spontaneous sputum collected. Se and Sp based on cutoff ROC curve
Kalomenidis et al (2004)	All	Benign pulmonary disease	IRMA	CEAa			57	95		Se and Sp based on cutoff ROC curves
			IRMA	NSEa			19	95
			IRMA	CYFRA 21-1a			36	95
Hillas et al (2008)b	All	COPD	IRMA	CEA			NS	NS	cases 4/50 (8%)	CEA median concentration. Cases: 713 ng ml−1, controls 518 ng ml−1
			IRMA	NSE			NS	NS		NSE median concentration. Cases: 12 ng ml−1, controls 13.7 ng ml−1
			RIA	CYFRA 21-1a			86	75

Abbreviations: All=all types of lung cancer included; CEA=carcinoembryonic antigen; COPD=chronic obstructive pulmonary disease; IRMA=immunoradiometric assay; NSE=neuron-specific enolase; NS=not specified; RIA=radioimmunoassay; ROC=receiver operating characteristic; RT–(Q)(N)–PCR=reverse transcriptase (quantitative) (nested)–polymerase chain reaction; Se=sensitivity; Sp=specificity; TRAP=telomeric repeat amplification protocol.

^aP<0.05 significance level between cases and controls.

^bInduced sputum.