SERPINB5 (maspin) is a serine protease inhibitor regulated by TP53 that has putative tumor suppressor functions. It is involved in mammary gland development via EGFR signaling. In cancer, both the degree of expression and the cellular localization of SERPINB5 correlates with stage and progression in some cancers. For example, SERPINB5 has generally nuclear positivity in normal epithelium, and primarily cytoplasmic localization of SERPINB5 is associated with tumorigenesis in lung, prostate and esophageal adenocarcinoma. Cytoplasmic SERPINB5 may be a useful early diagnostic biomarker for the transformation of normal epithelia and Barrett’s esophagus into esophageal adenocarcinoma; overall expression of SERPINB5 appears to decrease with stage and cellular distribution trends from nuclear to cytoplasmic alongside progression. SERPINB5 expression is lost in invasive subtypes, and predominantly cytoplasmic expression may be indicative of pre-neoplastic lesions with a greater risk of progression to adenocarcinoma. Dzinic et al have indicated that SERPINB5 may only have tumor suppressive functions while localized to the nucleus, where it suppresses HDAC1 suppression, plays a role in chromatin folding and contributes to genetic stability. Predominantly cytoplasmic expression and absence in the nucleus may thus lead to an increase in DNA mutations and ultimately promote tumor cell survival. In immunohistochemistry of normal tissue, SERPINB5 has both cytoplasmic and nuclear positivity in the esophagus, prostate, skin, intestine, lung, cerebral cortex, thymus, testis and tongue. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Neurol Res. 2010 Apr;32(3):303-8, PMID: 19909580; Science. 263 (5146): 526–9, PMID: 8290962; PLoS One. 2016; 11(7): e0159856, PMID: 27447178; PLoS One. 2019 Apr 19;14(4):e0215089, PMID: 31002675; Cancer Res. 2006 Sep 15;66(18):9323-9, PMID: 16982778