Glassy Cell Carcinoma Predominantly Commits to a Squamous Lineage and is Strongly Associated with High-risk Type Human Papillomavirus Infection

Glassy cell carcinoma (GCC) has been believed to have originated from reserve or uncommitted cells as a poorly differentiated adenosquamous carcinoma. This study includes immunoprofiles of p63, cytokeratin 17 (CK17), and CD44 to clarify which lineage of GCC is committed to human papillomavirus (HPV) detection, and to verify whether or not HPV plays a role in GCC. Nine uterine GCCs showing overwhelmingly glassy features were evaluated by an HPV genotyping chip and by immunohistochemistry for E-cadherin, CD44, p63, CEA, erb-B2, cytokeratin 17, and p16. An HPV genotyping DNA chip array with multiple oligonucleotide probes of L1 sequences from 26 types of HPV was introduced. GCCs were variably stained, except for CD44 which was stained unanimously. A lack of E-cadherin was found in 4 cases, frequent expression of p63 in 6/9 (66.7%), mucin stain or CEA in 5/9 (55.6%), and coexpression of p63 in 4. HPV prevalence in GCC was found in 6/9 cases (66.7%). HPV-18 and HPV-32 were the most common types detected. The remaining cancers were infected by HPV-31, HPV-35, HPV-39, and HPV-68. Multiple infections were found in 2 out of 6 cases. GCC could not be precisely categorized, but was committed to squamous lineages and was strongly associated with high-risk type HPV infection.