Abstract
Squamous cell carcinoma antigen (SCCA) belongs to the serine protease inhibitor (Serpin) family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC) in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360) and normal breast epithelium (n = 124). SCCA expression was scored on a tiered scale (0-3) independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%), Grade II (2.5%), and Grade III (9.4%) breast cancers (p<0.0001). Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005). No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124). SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR) double-negative tumors (p = 0.0009). Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively). This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment.
Highlights
Squamous cell carcinoma antigens (SCCA) are members of the serpin family of endogenous serine proteinase inhibitors
The 8H11 antibody, which was described to recognize SCCA1 (Santa Cruz Biotechnology Product Information; [8]), failed to do so in our hands. These results indicate that Clone FL-390 is a reliable and more efficient antibody for recognizing both SCCA1 and SCCA2
Studies have shown that the SCCA levels in the serum of cervical squamous cell carcinoma patients correlates with the severity of the cancer [18]
Summary
Squamous cell carcinoma antigens (SCCA) are members of the serpin family of endogenous serine proteinase inhibitors. The first variant of SCCA, SCCA1, was originally identified in squamous cell carcinoma (SCC) of the uterine cervix [1]. Further studies found that SCCA1 and its isoform, SCCA2, are produced by two tandemly arranged genes located on chromosome 18q21 [2]. SCCA1 and SCCA2 are approximately 98% and 92% homologous at their nucleotide and amino acid levels, respectively. SCCA1 and SCCA2 inhibit different classes of proteases, dictated by differences in amino acids located in the reactive site loop (RSL), both isoforms are expressed in stratified squamous epithelia and have been found to be produced in SCCs [3,4]. Immunohistochemistry on tissue biopsies and ELISA-based detection of circulating SCCA (including both SCCA1 and SCCA2) are currently used as valuable predictors of nodal metastasis, response to treatment, and tumor recurrence in SCCs of the uterine cervix, lung, head and neck, esophagus, and liver [5,6]
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