The Clinical Significance of K-Ras Mutation in Endometrial "Surface Epithelial Changes" and Their Associated Endometrial Adenocarcinoma
Jinjun Xiong, Mai He, Cynthia L Jackson, Virgina Breese, Katrine Hansen, W Dwayne Lawrence. Women & Infants Hospital, Alpert Medical School of Brown University, Providence, RI; Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI
Background: The entity of so-called 'surface epithelial changes' (SECs) was first described in 1995. Morphologically, SECs usually arise directly from malignant glands at the most superficial aspect of endometrioid carcinomas (EC) and impart the appearance of a 'maturational' phenomenon at the surface of the cancer. SECs typically show bland mucinous, syncytial, squamoid, and papillary features that mimic a variety of benign entities, particularly endocervical microglandular hyperplasia. Studies have reported SECs to be associated with approximately half of ECs many of which showed focal mucinous differentiation. Therefore, despite their morphologically benign histology, some workers have questioned whether the presence of SECs represents a 'marker' for an underlying malignancy. Since the biologic nature of SECs is unknown, we aimed to study the prevalence of K-ras gene mutations in SECs and the underlying EC from which they directly arise.
Design: 14 cases with biopsy proven SECs and ECs in their subsequent hysterectomies were retrieved from our institutional archives. In 8 of 14 cases, only SECs were present in the endometrial biopsy but ECs were found in each uterine corpus after hysterectomy. 6 endometrial samplings showed concomitant SECs and ECs. All tumors associated with SECs were so-called 'type 1' ECs. Genomic DNA, derived from microdissected SECs and ECs to ensure >80% lesional cells, was extracted from formalin-fixed paraffin-embedded tissue sections. PCR amplification for K-ras codons 12 and 13 was performed with subsequent sequencing by capillary electrophoresis.
Results: K-ras codons 12 and 13 mutations were detected in 11 of 14 (78%) SECs and 11 of 14 (78%) ECs. 9 of 11 point mutations were identified at codon 12 with the most prevalent mutation (4 of 9) being G12D (codon 12; GGT > GAT). Only 2 point mutations were seen at codon 13, both being G13D. All SECs had the same k-ras mutation as their underlying EC.
Conclusions: 78% of cases with SECs had K-ras mutations, and in each case the mutation in the SECs was identical to that in the associated underlying ECs. These findings strongly suggest that SECs, despite their bland appearance and varied histology, are neoplastic surface manifestions of the underlying EC. Therefore, their presence in endometrial biopsies/curettages, particularly in postmenopausal women, should raise suspicion for an associated EC.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 11:30 AM
Platform Session: Section E, Tuesday Morning