Clinical significance of sperm protein 17 expression and immunogenicity in esophageal cancer.
We recently identified sperm protein 17 (Sp17) transcripts in esophageal squamous cell carcinomas (ESCCs) by differential display. This study was designed to determine the clinical significance of Sp17 protein in different stages of esophageal tumorigenesis and to test the hypothesis that aberrant localization of Sp17 protein to immunosurveillant site may lead to production of anti-Sp17 antibodies in serum, which may be of clinical relevance in ESCCs. Sp17 transcripts were detected by RT-PCR in 26 of 30 (86%) ESCCs, while no transcripts were detected in normal esophageal tissues. Rabbit polyclonal antibody was raised against an immunogenic peptide of Sp17 and used to evaluate protein expression by immunohistochemistry. Expression of Sp17 protein was observed in 60/80 (75%) of ESCCs and 27/30 (90%) dysplastic tissues, while no detectable Sp17 expression was observed in 13 distant histologically normal epithelia. Sixteen of the 60 immunopositive ESCCs showed nuclear expression in addition to cytoplasmic localization of the protein. The circulating levels of anti-Sp17 antibodies, determined by ELISA, were significantly elevated in ESCC patients when compared with normal subjects (p < 0.001). Increasing Sp17 antibody titers were observed to be associated with the progressive disease in 4 patients. In conclusion, the study demonstrates expression of Sp17 protein in esophageal tumor as well as dysplastic tissues, suggesting it to be an early event in the development of ESCC. To our knowledge, this is the first report showing elevated levels of anti-Sp17 antibodies in ESCC patients.
Gupta
Garima
G
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Sharma
Rinu
R
Chattopadhyay
Tushar K
TK
Gupta
Siddarth D
SD
Ralhan
Ranju
R
D000328:Adult; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004947:Esophagus / Q000276:immunology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000912:Antibodies, Neoplasm; D000954:Antigens, Surface; D001324:Autoantigens; D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C090172:SPA17 protein, human