k-ras mutation may be an early event in mucinous ovarian tumorigenesis

We explored the possible pathogenetic pathway for mucinous ovarian tumorige nesis by examining the k-ras mutational patterns in ovarian mucinous tumors (OMTs) with benign, borderline, and invasive epithelium in which the diffe rent types of mucinous epithelium are in close proximity. Sixteen patients with ovarian mucinous borderline tumors (OMBTs) and 4 patients with grade 1 ovarian mucinous adenocarcinomas (OMCs) were selected for the presence of a single histologic section which contained a clear "transition" zone from benign mucinous epithelium to borderline mucinous epithelium, and in four c ases, to invasive epithelium. A PixCell II Laser Capture Microscope was use d to microdissect and retrieve benign, borderline, and invasive epithelium separately from the 20 OMTs. Normal ovarian stroma from the same histologic section in each case was also microdissected and retrieved for use os a co ntrol. k-ras mutations were detected in these samples by PCR-SSCP analysis followed by direct PCR cycle sequencing, k-ras mutations were found in 8/16 (50%) of the OMBTs and 2/4 (50%) of the grade 1 OMCs. In 6 of these 10 cas es (4 in OMBTs, 2 in grade 1 OMCs), the same k-ras mutation was found in bo th the benign and borderline land invasive) regions. In 3 cases in which k- ras mutations were identified, the mutation was found in either the benign or borderline tissue samples alone, and in one case, two distinct mutations were found. No k-ras mutations were identified in the normal ovarian strom a. The presence of a k-ras mutation in adjacent benign and borderline regio ns of a single OMT may suggest a progression in the development of OMTs fro m benign to borderline and grade 1 OMCs. k-ras mutations, when they occur, are likely early genetic changes but may not alone be sufficient for malign ant transformation of ovarian epithelium.