KRAS mutations in mucinous lesions of the uterus

Objectives: The current study examined the KRAS mutation status in a spectrum of mucinous lesions of the uterus, including mucinous metaplasia (MM), atypical mucinous proliferation (AMP), endocervical mucosa, and microglandular hyperplasia (MGH). Methods: Thirty-nine cases, including 15 AMPs, nine MMs, nine MGHs, and six normal endocervical mucosas, were selected from the departmental archive. All AMP cases with follow-up biopsies or hysterectomies were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and KRAS codons 12 and 13 sequence analyzed. Results: KRAS codon 12 and 13 mutations were detected in 10 (67%) of the 15 AMP cases. No KRAS mutations were identified in MMs, MGHs, and endocervical mucosas (P = .002, AMP vs MM or MGH, Fisher exact test). Most women with AMP were postmenopausal (13/15 [86.7%]) and presented with dysfunctional uterine bleeding. Among the 10 cases of AMP harboring KRAS mutations, six (60%) cases were subsequently diagnosed with carcinoma, one with atypical complex hyperplasia, and two with AMP within endometrial polyps. Conclusions: The results suggest a possible association between KRAS mutations and mucinous differentiation in endometrial carcinogenesis. KRAS status can help in assessing benign from precursor or malignant mucinous lesions as well as differentiate endometrial lesions from those of cervical origin.