Gynecologic & Obstetrics

ANNUAL MEETING ABSTRACTS Table 2. IHC for p63 and p40 in MPUC, LGUC or HGUC component of all cases studied and in tumors of different stages. MPUC HGUC LGUC <T2 ≥T2 Marker Positivity P values (n=20) (n=69) (n=42) (n=36) (n=62) P1 < 0.001, Positive 86.1 ± 64.2 ± P2 < 0.001, p63 Tumor Cells 0.0 ± 0.0 37.1 ± 30.9 22.3 ± 29.6 6.0 32.6 P3 < 0.001, (%) P4 < 0.001 P1 < 0.001, Positive 89.8 ± P2 < 0.001, p40 Tumor Cells 0.5 ± 1.5 51.4 ± 28.2 68.3 ± 32.6 38.5 ± 33.6 5.8 P3 < 0.001, (%) P4 < 0.001 Student T test. P1: MPUC vs. HGUC; P2: MPUC vs. LGUC; P3: HGUC vs. LGUC; P4: <T2 vs.≥T2 Conclusions: p63 expression is seen diffusely in all LGUCs, significantly decreased in HGUC and lost in MPUC. p40 expression is also decreased in HGUC and markedly decreased in MPUC. Based on these results, loss of p63 expression in a UC appears to be associated with adverse features—namely high grade, high stage, or MPUC. p40 is more frequently expressed in urothelial carcinoma irrespective of tumor grade, stage, or MPUC when compared to p63 and thus, may be a superior diagnostic marker than 4A4(p63). Further study including more cases and other UC variants are needed to substantiate these findings. 1611 Added Value of ERG to PIN Cocktail for Evaluation of Atypical Small Acinar Proliferations (ASAP) of Prostate EE Chang, DJ Luthringer, M de Peralta-Venturina, MB Amin. Cedars-Sinai Medical Center, Los Angeles, CA. Background: High correlation with prostate cancer (PCa) potentiates ERG as an additional marker to the PIN cocktail in determining ASAP versus PCa diagnosis. ERG is positive in 11-16% of atypical biopsies, but previous studies do not directly address the added diagnostic value of ERG to the PIN cocktail. This study determines the impact of ERG on the final diagnosis beyond assessment based on H&E and PIN cocktail (HE+PIN). Design: Biopsies from 7/2010-5/2012 diagnosed as ASAP after HE+PIN (PINATYP excluded) were stained retrospectively with ERG(EPR3864). All cores with ASAP by H&E received from 6/2012-9/2012 were evaluated with PIN cocktail and ERG results. Subsequently, all ERG-positive cases from both arms were independently reviewed by 3 urologic pathologists to render diagnostic impression based on H&E only, HE+PIN, and HE+PIN+ERG evaluation. A negative ERG result is non-contributory. Results: In the 107 retrospective cases, ERG was negative in 97. Of the 10(9%) ERGpositive cases, 3 cases by majority and 1 unanimously were upgraded from ASAP to PCa based on HE+PIN evaluation given absent basal cells and variably upregulated racemase. After HE+PIN+ERG, 1 case was upgraded to PCa based on ERG staining while 5 remained ASAP: 4 due to presence of rare basal cells despite increased racemase, 1 considered insufficient malignant histology by majority. In the prospective arm, ERG was positive in 3/24(13%). After HE+PIN, converted diagnoses were 13(54%) PCa and 5(21%) benign. One PCa was ERG-positive; benign cases were all ERG-negative. Of the remaining 7(29%) ASAP cases, 2 were positive for ERG: 1 was converted to PCa, the other remained ASAP due to weak inconsistent staining in suspicious glands and weak positivity in morphologically benign glands. In total, ERG was positive in 10%(13/131) of ASAPs; ERG impacted the diagnosis in 1.5%(2/131) of ASAPs. Conclusions: The difficulty in achieving unanimous consensus diagnosis highlights the subjective aspect of HE+PIN interpretation and ASAP designation. ERG positivity adds to the malignant quality of atypical glands, but whether this contribution to histology and PIN exceeds the threshold for diagnosis of PCa varies. Regardless, overall ERG positivity in ASAP is low, and even within ERG-positive cases, the same conclusion was often achieved by just HE+PIN. ASAPs with at least rare basal cells were never designated as PCa, and it is unlikely ERG would change this. The limited added utility should be considered with costs and resources for its upfront use in routine evaluation of ASAP within standard practice. 263A with microglandular pattern, 7 of which were also subjected to K-ras mutation analysis. Results: Fifteen of the 45 MGH cases (33.3%) had 5 or more mitoses/10 HPF. The highest mitotic count was 11/10 HPF, which was observed in 3 cases. Moderate cytologic atypia was seen in 13 MGH cases. Follow-up was available for 29 MGH patients (mean follow-up time 37 months), all of which were alive and well. K-ras mutation was absent in all 10 MGH cases tested. In the EAC group, 4 of the 7 cases tested positive for K-ras mutation. Conclusions: MGH of the cervix may show significant mitotic activity (up to 11/10 HPF) in a relatively high proportion of cases without negatively affecting the clinical prognosis. Therefore, mitotic activity cannot be reliably used to differentiate between MGH and EAC in small biopsies. K-ras mutation analysis may be a helpful adjunct in difficult cases. 1096 Genetic Reclassification of Undifferentiated Endometrial Sarcoma: Clinical Relevance RH Ali, S Kurihara, M Endo, M Rouzbahman, LN Hoang, N Melnyk, A MarinoEnriquez, P Dal Cin, JA Fletcher, E Oliva, DG Huntsman, Y Oda, MR Nucci, C-H Lee. University of British Columbia, Vancouver, Canada; Kyushu University, Fukuoka, Japan; University of Toronto, Toronto, Canada; Brigham and Women’s Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; British Columbia Cancer Agency, Vancouver, Canada. Background: Undifferentiated endometrial sarcoma (UES) is the current designation for tumors formerly considered as high-grade endometrial stromal sarcoma (ESS). Some UES exhibit uniform nuclear features (UES-U) whereas others exhibit nuclear pleomorphism (UES-P). We recently identified YWHAE-FAM22 genetic rearrangement in tumors diagnosed as UES or high-grade ESS. YWHAE-FAM22 tumors are clinically more aggressive than low-grade ESS with JAZF1-SUZ12 genetic rearrangement, but it is yet unclear whether YWHAE-FAM22 tumors differ in clinical course from UES lacking YWHAE-FAM22. Design: We employed YWHAE-FAM22 split-apart fluorescence in situ hybridization and RT-PCR assays to genetically classify 50 UES/high-grade ESS as YWHAE-FAM22 ESS vs. YWHAE-FAM22-negative UES (UES-U and UES-P). Results: Of the 50 tumors, 12 showed appreciable nuclear pleomorphism at 40x magnification (UES-P) and none of these had YWHAE-FAM22 rearrangement. Among the 38 tumors with uniform nuclear features, 24 had YWHAE-FAM22 rearrangement (YWHAE-FAM22 ESS), including 12 with focal low-grade component that mimicked classic low-grade ESS. The remaining 14 cases with uniform nuclear features lacked apparent YWHAE-FAM22 rearrangement (UES-U). The clinical features are shown in Table 1 with the result of Kaplan-Meier analysis shown in Figure 1. Table 1 Age (average +/- SE) FIGO (1988) stage 1 2-4 Follow-up (with >1 year) Died of disease Alive with disease Alive with no disease Adjuvant therapy Chemotherapy and/or radiation None YWHAE-FAM22 46 +/- 3 UES-U 55 +/-5 UES-P 60 +/-3 6 (27%) 16 (73%) 5 (42%) 7 (58% (...truncated)