Peter W. Schlosshauer

Prophylactic oophorectomy: a morphologic and immunohistochemical study.

The tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia‐associated markers in prophylactically removed ovaries, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium.

A comparative analysis of 57 serous borderline tumors with and without a noninvasive micropapillary component.

The literature concerning serous borderline tumors with a noninvasive micropapillary component suggests an association with invasive implants. We compared the clinicopathologic features of micropapillary serous borderline tumors (MSBTs) with typical SBTs to determine the following: 1) the importance of focal micropapillary architecture in an otherwise typical SBT, 2) the behavior of low-stage MSBTs, 3) whether high-stage MSBTs are inherently more aggressive than high-stage SBTs, and 4) whether invasive implants are prevalent in an MSBT cohort without referral selection bias. The 57 borderline tumors studied were diagnosed at a university hospital between 1981 and 1998; they included 14 MSBTs, 35 SBTs, and 8 SBTs with focal micropapillary features. None of the specimens were referrals for expert pathologic consultation, thus distinguishing our study group from most of those previously reported. Neither MSBTs nor SBTs were associated with invasive implants at diagnosis (0 of 14 and 0 of 43, respectively). They also did not differ with respect to overall stage at diagnosis, but MSBTs were more frequently bilateral than SBTs (71% versus 23%, p = 0.001). There was an increased risk of recurrence in MSBT versus SBT (3 of 14 versus 1 of 43, p = 0.035), but this was stage related; there was no difference between groups when evaluating recurrence in stage I disease (0 of 8 versus 0 of 27). There was no difference in recurrence or stage at diagnosis between SBTs with focal micropapillary features and other SBTs. There was 100% survival in all groups. We conclude that high-stage MSBTs with noninvasive implants should be considered a subtype of SBTs with an increased risk of recurrence. Stage I MSBTs demonstrate clinical features that are similar to low-stage SBTs. Focal micropapillary architecture (<5 mm) has no bearing on outcome. MSBTs in the general population are not strongly associated with invasive implants.

Rapamycin by Itself and Additively in Combination with Carboplatin Inhibits the Growth of Ovarian Cancer Cells

OBJECTIVE The current standard treatment for ovarian carcinoma, consisting of surgery followed by chemotherapy with carboplatin and paclitaxel, is fraught with a high rate of recurrences. We hypothesized that targeted inhibition of specific signaling pathways in combination with conventional drugs may increase chemotherapeutic efficacy. METHODS We analyzed the expression and activation profiles of various signaling pathways in nine established ovarian cancer cell lines (CAOV-3, ES2, PA-1, SKOV-3, NIHOVCAR3, OV90, TOV112D, A1847, A2780) and 24 freshly procured human ovarian tumors. The PI3 kinase pathway component Akt was frequently overexpressed and/or activated in tumor cells. The effect of several PI3K pathway inhibitors (rapamycin, LY294002, SH-6) and rapamycin in combination with carboplatin on various tumor cell growth characteristics was tested in cell lines and fresh tumor-derived transient monolayer and organ cultures. RESULTS Rapamycin by itself and additively with carboplatin inhibited the growth and invasion, and increased the sensitivity to anoikis of most of the ovarian cancer cell lines and fresh tumors. The additive inhibitory effect may be due to enhanced apoptosis as demonstrated by Poly-ADP-Ribose Polymerase (PARP) cleavage and Annexin V staining in cells treated with both rapamycin and carboplatin. CONCLUSIONS Rapamycin in combination with standard chemotherapeutic agents may improve the efficiency of ovarian cancer treatment.

Loss of p16INK4A expression in low-grade ovarian serous carcinomas.

According to a tumor progression model, low-grade ovarian serous carcinomas may evolve from serous borderline tumors or micropapillary tumors. We sought to investigate the role of and associations between BRAF mutational status, extracellular signal regulated kinase activation, and p16INK4A expression in various types of ovarian serous tumors. We analyzed 29 typical ovarian serous borderline tumors, 8 micropapillary tumors, 4 low-grade invasive ovarian serous carcinomas, and 24 high-grade invasive ovarian serous carcinomas for the BRAF mutational status at codon 600; in addition, expression levels of the downstream signaling protein extracellular signal regulated kinase and the p16INK4A tumor suppressor protein were assessed by immunohistochemistry. There was a decline in p16INK4A expression from serous borderline tumors to micropapillary tumors with almost complete loss in low-grade invasive carcinomas. High-grade carcinomas had a variable p16INK4A expression pattern. We found a T1799A BRAF mutation in 12 typical serous borderline tumors (41%) and 1 micropapillary tumor (12.5%). No mutations were found in the low-grade and high-grade invasive carcinomas (0%). Among the typical borderline tumors, cases with BRAF mutations tended to have stronger p16INK4A expression compared with cases with wild-type BRAF. No other correlations were identified between the BRAF mutational status and expression levels of the analyzed proteins. Loss of p16INK4A expression may be a pathogenetic factor in the progression from serous borderline tumors to low-grade invasive carcinomas. The divergent molecular profiles support the theory that high-grade carcinomas are unrelated to serous borderline tumors or low-grade carcinomas.

Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer

BackgroundRNA-Seq allows a theoretically unbiased analysis of both genome-wide transcription levels and mutation status of a tumor. Using this technique we sought to identify novel candidate therapeutic targets expressed in epithelial ovarian cancer (EOC).MethodsSpecifically, we sought candidate invasion/migration targets based on expression levels across all tumors, novelty of expression in EOC, and known function. RNA-Seq analysis revealed the high expression of CD151, a transmembrane protein, across all stages of EOC. Expression was confirmed at both the mRNA and protein levels using RT-PCR and immunohistochemical staining, respectively.ResultsIn both EOC tumors and normal ovarian surface epithelial cells we demonstrated CD151 to be localized to the membrane and cell-cell junctions in patient-derived and established EOC cell lines. We next evaluated its role in EOC dissemination using two ovarian cancer-derived cell lines with differential levels of CD151 expression. Targeted antibody-mediated and siRNA inhibition or loss of CD151 in SKOV3 and OVCAR5 cell lines effectively inhibited their migration and invasion.ConclusionTaken together, these findings provide the first proof-of-principle demonstration for a next generation sequencing approach to identifying candidate therapeutic targets and reveal CD151 to play a role in EOC dissemination.

Laparoscopic morcellation of didelphic uterus with cervical and renal aplasia.

Laparoscopic morcellation of the obstructed hemiuterus may be the preferred treatment of this congenital anomaly following failure of a surgical cervical fistula.

Early pathologic diagnosis of gynecologic cancer including a clinician's view

Early Diagnosis of Vulvar Cancer Early Diagnosis of Cervical Cancer Early Diagnosis of Endometrial Cancer Early Diagnosis of Ovarian Cancer A Clinicians View of Early Diagnosis of Gynecologic Cancer.