Primary squamous cell carcinoma of the endometrium: clinicopathologic and molecular characteristics.

Molecular alterations leading to cell cycle dysregulation in primary squamous cell carcinoma of the endometrium (PSCCE) and correlation with clinical outcome are incompletely described. Molecular variables of 5 cases of PSCCE were compared with 8 controls of endometrial endometrioid adenocarcinoma and correlated with overall survival. Immunohistochemical expression of pRB, p18, p19, CDK4, CDK6, Cyclin D1, p16, HPVE7, pTEN, ER, PR, and p53 was independently scored (intensity: 0-3 and proportion: 0-5) twice by 2 reviewers. Scores were averaged and expression was categorized as positive or negative. Human papillomavirus (HPV) DNA amplification and Braf and Kras mutations were assessed by polymerase chain reaction. Distribution differences between cases and controls were tested for significance using χ/Fisher exact tests. Differences in overall survival and correlation with variables were calculated using Kaplan-Meier and tested for significance using log rank tests. All cases and controls were mostly positive for pRB, p19, CDK6, and Cyclin D1 and mostly negative for p16, p18, CDK4, HPVE7, pTEN, and p53. Cases were mostly negative for ER and PR, whereas controls were mostly positive. All were negative for HPV DNA amplification and Braf mutations. One case and 2 controls had a Kras mutation. Only the ER and PR distribution difference was significant (P=0.03 and 0.02, respectively) and differences in overall survival did not correlate with any variable. PSCCE has molecular alterations involving the pRB-Cyclin D1-CDK4/6-p16 pathway, and pTEN. In contrast to the type I EACC, PSCCE is not hormonally sensitive, suggesting a unique pathogenesis.