%0 Journal Article
%T P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas
%A Dinka Sundov
%A Ana Caric
%A Ivana Mrklic
%A Dijana Gugic
%A Vesna Capkun
%A Irena Drmic Hofman
%A Branka Petric Mise
%A Snjezana Tomic
%J Diagnostic Pathology
%D 2013
%I BioMed Central
%R 10.1186/1746-1596-8-21
%X Eighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples.Of 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P£¿<£¿0.001) and topoII alpha (P£¿=£¿0.001), with Ki67 median 56.5 vs. 19 in low-grade group (P£¿<£¿0.001). The difference in immunoexpression of active MAPK between low- and high-grade group was also significant (P£¿=£¿0.003). MAPK positive immunostaining was detected in 63.6% of low-grade vs. 17.1% of high-grade OSCs. The frequency of KRAS mutation was significantly higher in low-grade as compared to high-grade group (P£¿=£¿0.006). None of the samples had BRAF mutation. In addition, we detected positive MAPK immunoexpression in 13/59 samples with wild-type KRAS, suggesting that activation of MAPK pathway is not ultimately related either to KRAS or BRAF mutation. Seven morphologically high-grade samples (11.7%) showed both KRAS mutation and p53 immunopositivity.Although this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears to be quite reliable in ruling out a KRAS mutation if the staining is negative.The virtual slide(s) for this article can be found here: h
%K Ovary
%K Serous Carcinomas
%K Carcinogenesis
%K Type I
%K Type II
%K Ovar
%K ser£¿se Karzinome
%K Karzinogenesis
%K Typ I Tumoren
%K Typ II Tumoren
%U http://www.diagnosticpathology.org/content/8/1/21