Table 1. Timeline of diagnostic technologies used for the detection of tumor autoantibodies in cancer.

Year of invention	Technology for tumor autoantibody detection	Application in cancer diagnostics	References
1965	Radioiodination of serum antibody	This technology was applied to determine the in vivo localization of radioantibodies in human brain tumors using animal models.	[24]
1966	Passive haemagglutination	Tumor autoantibodies were detected in patients with colonic cancer or other diseases.	[94]
1968	Immunofluorescence	Presence of tumor autoantibodies against malignant human melanoma was demonstrated in this study.	[63]
1970	Compliment fixation method and Passive agglutination technique	Autoantibodies against T like antigen were detected in breast carcinoma.	[88]
1975	Indirect Immunofluoresence	Tumor autoantibodies were detected in patients with breast carcinoma.	[100]
1979	Radioiodination of Staphylococcus protein A (SPA)	This assay was employed for the detection of antibodies in melanoma and colon carcinoma patients.	[66]
1982	Immunoprecipitation and sodium dodecyl poly-acrylamide gel (SDS-PAGE)	Autoantibodies against cellular p53 were detected in the sera obtained from patients with breast cancer.	[22]
1985	Immunoelectrophoresis and radioimmunoelec-trophoresis In conjunction with I-125 labeled CEA	Autoantibodies against CEA were detected in the serum of colonic cancer patients.	[90]
1986	Polyethylene glycol (PEG) and C1q solid-phase microassay (C1q-SPMA)	Circulating immune complexes were detected in sera or ascites of patients with hepatocellular carcinoma.	[18]
1989	Adapted immunoenzymatic assay (ELISA method)	This technolgoy was applied for the detection of autoan-tibodies against membrane phospholipids such as, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, ganglioslides, sphingomyelin, sph-ingosin, and cardiolipin in the serum of patients with malignant tumors.	[29]
1990	Avidin-biotin immunoperoxidase method and highly sensitive quantitative western blot analysis	Anti-Hu antibodies were detected in the serum of patients diagnosed with small cell lung cancer.	[23]
1994	Recombinant baculovirus containing tumor Ag and western blot	Autoantibodies to Her2/neu were detected in breast cancer patients.	[25]
1995	Enzyme linked immunosorbent assay (ELISA)	This technology was used for the detection of serum p53 antibodies in patients with benign or malignant pancreatic and biliary diseases. Another group reported the detection of p53 antibodies in the sera of lung cancer patients in the same year.	[48,103]
1995	SEREX technology3	Circulating autoantibodies against melanoma antigens, renal carcinoma antigens, brain tumor antigens, antigens expressed in Hodgin diseases were detected in serum of cancer patients.	[78]
1996	This methodology was basedonthe preparation of bacterially synthesized glutathione S-transferase (GST)-tumor Ag fusion proteins and western blot analysis	Autoantibodies directed against L-myc oncogene products were detected in the sera of patients with lung cancer.	[106]
1996	Time-resolved immunofluorometric procedure	Circulating p53 antibdies were detected in patients with ovarian carcinoma.	[5]
1997	SEREX technology	Autoantibodies against cancer testis antigen NY-ESO-1 were detected in osephageal squamous cell carcinoma patients.	[19]
1998	SEREX technology	Forty eight human colon cancer antigens (NY-CO-1-NYCO-48) were identified by SEREX analysis in patients with colon cancer.	[79]
1998	ELISA (PEM.C1g) employed a 60 mer MUC1 peptide conjugated to bovine serum albumin and peroxidase-labeled antihuman immunoglobulin G or M antibodies	Circulating antibodies to polymorphic epithelial mucin (MUC1) were detected in breast and ovarian carcinoma patients.	[93]
2000	Indirect immunofluorescence test (IFT)	Antineural and antinuclear autoantibodies were detected in patients with non-small cell lung cancer.	[7]
2000	SDS-PAGE and western blot analysis	This technology was applied for the detection of antibodies against endostatin in patients with multifocal glioblastoma.	[73]
2001	Two dimensional (2D) PAGE, western blotting, and Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)	Occurrence of autoantibodies against novel tumor antigen RS/DJ-1were detected in breast cancer patients.	[49]
2002	ELISA, immunoblot and indirect fluorescence.	p53 antibodies were detected in breast cancer.	[92]
2003	Two dimensional liquid chromatography and protein microarrays	The study showed that microarrays of fractionated proteins could be a powerful tool for tumor antigen discovery and cancer diagnosis.	[10]
2005	Expression of recombinant tumor antigen, SDS-PAGE, western blotting and ELISA	Increased level of Fas (CD95) autoantibodies was detected during colon carcinogenesis.	[74]
2006	Expression of recombinant His-tagged tumor Ag, and ELISA	Circulating autoantibodies of cancer testis antigen NY-ESO-1 were detected in lung cancer patients.	[89]
2006	SEREX and Luminex technology	Autoantibodies against IL-8 were elevatedinpatients with ovarian cancer.	[54]
2006	Epitomics: Combination of phage display cloning of tumor Ag, differential biopanning and protein microarray	Autoantibodies directed against 65 tumor antigens were detected in patients with ovarian cancer.	[16]
2006	Reverse capture autoantibody microarray	This technology was applied for antigen-autoantibdy profiling with sera from prostate cancer and benign prostate hyperplasia.	[70]
2007	Serological proteome profiling (SERPA)	Autoantibodies signatures produced in response to the breast or colorectal cancer was reported.	[39]
2008	Nucleic acid programmable protein microarray (NAPPA) and ELISA	This technology reported that of 1705 nonreduntant expressed antigens, dominant antibodies were detected in patients diagnosed with melanoma, breast and ovarian cancer.	[3]
2008	Luminex bead array technology	This technology allowed rapid detection of tumor autoantibody repertoire in the serum of cancer patients using in vitro expressed epitope-tagged tumor Ag (either GST or FLAG tagged) that were captured later onto anti-epitope coupled Luminex SeroMap beads.	[105]
2010	Chemoenzymatic synthesis of O-glycopeptides and O-Glycopeptide array print	Autoantibody signatures to aberrant O-glycopeptide epitopes in the serum of cancer patients were reported.	[96]
2010	RAPID ELISA	Autoantibodies to p53 were detected in 42% of patients with advanced serous ovarian cancer.	[4]

³SEREX database can be found at their web site (http://ludwig-sun5.unil.ch/CancerImmunomeDB/).