High-molecular weight keratin (HMWK, HMWCK) refers to the group of large cytokeratins KRT1, KRT5, KRT10 and KRT14. Antibodies to HMWK are used to identify prostate basal cells and also squamous, ductal and other epithelial cells. HMWK is also positive in thyroid solid cell nests. Clone 34betaE12 (CK903) recognizes KRT1, KRT5, KRT10 and KRT14, while DE-SQ recognizes KRT13, KRT14, KRT15 and KRT16. HMWK antibodies should have strong cytoplasmic staining. They are used in the diagnosis of prostate cancer to determine presence of basal cells and to differentiate PIN (prostatic intraepithelial neoplasia, HMWK positive) and small benign acinar lesions (positive) from adenocarcinoma (typically negative). Furthermore, HMWK antibodies are used in breast cancer to distinguish lobular carcinoma in situ (positive) from ductal carcinoma in situ (negative). The list of HMWK-positive lesions also includes urothelial carcinoma, thyroid papillary carcinoma and CASTLE tumors, epithelioid mesothelioma, transitional cell carcinoma, nasopharyngeal carcinoma, high grade thymoma, squamous cell carcinoma, non-small cell carcinoma of the lung, kidney collecting duct carcinoma, endometrial carcinoma and ovarian clear cell carcinoma. HMWK is often paired with p63 and AMACR for increased sensitivity. References: Arch. Pathol. Lab. Med. 132 (3): 349–58, PMID: 18318578; Mod. Pathol. 15 (11): 1181–90, PMID: 12429797; Mod Pathol. 2004 Mar;17(3):360-79, PMID: 14739906; Am J Surg Pathol 2006;30:994, PMID:16861971; Int J Gynecol Pathol. 2001 Apr;20(2):155-9, PMID: 11293161; Appl Immunohistochem Mol Morphol 2000;8:42, PMID: 10937048