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Gynecologic &Amp ANNUAL MEETING ABSTRACTS 263A Table 2. IHC for p63 and p40 in MPUC, LGUC or HGUC component of all cases studied and in with microglandular pattern, 7 of which were also subjected to K-ras mutation analysis. tumors of different stages. Results: Fifteen of the 45 MGH cases (33.3%) had 5 or more mitoses/10 HPF. The MPUC HGUC LGUC <T2 ≥T2 Marker Positivity P values highest mitotic count was 11/10 HPF, which was observed in 3 cases. Moderate (n=20) (n=69) (n=42) (n=36) (n=62) P1 < 0.001, cytologic atypia was seen in 13 MGH cases. Follow-up was available for 29 MGH Positive 86.1 ± 64.2 ± P2 < 0.001, p63 Tumor Cells 0.0 ± 0.0 37.1 ± 30.9 22.3 ± 29.6 patients (mean follow-up time 37 months), all of which were alive and well. K-ras 6.0 32.6 P3 < 0.001, (%) mutation was absent in all 10 MGH cases tested. In the EAC group, 4 of the 7 cases P4 < 0.001 P1 < 0.001, tested positive for K-ras mutation. Positive 89.8 ± P2 < 0.001, Conclusions: MGH of the cervix may show significant mitotic activity (up to 11/10 p40 Tumor Cells 0.5 ± 1.5 51.4 ± 28.2 68.3 ± 32.6 38.5 ± 33.6 5.8 P3 < 0.001, HPF) in a relatively high proportion of cases without negatively affecting the clinical (%) P4 < 0.001 prognosis. Therefore, mitotic activity cannot be reliably used to differentiate between Student T test. P1: MPUC vs. HGUC; P2: MPUC vs. LGUC; P3: HGUC vs. LGUC; P4: <T2 MGH and EAC in small biopsies. K-ras mutation analysis may be a helpful adjunct vs.≥T2 in difficult cases. 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 1096 Genetic Reclassification of Undifferentiated Endometrial be associated with adverse features—namely high grade, high stage, or MPUC. p40 is Sarcoma: Clinical Relevance more frequently expressed in urothelial carcinoma irrespective of tumor grade, stage, RH Ali, S Kurihara, M Endo, M Rouzbahman, LN Hoang, N Melnyk, A Marino- or MPUC when compared to p63 and thus, may be a superior diagnostic marker than Enriquez, P Dal Cin, JA Fletcher, E Oliva, DG Huntsman, Y Oda, MR Nucci, C-H 4A4(p63). Further study including more cases and other UC variants are needed to Lee. University of British Columbia, Vancouver, Canada; Kyushu University, Fukuoka, substantiate these findings. Japan; University of Toronto, Toronto, Canada; Brigham and Women’s Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; British Columbia Cancer Agency, Vancouver, Canada. 1611 Added Value of ERG to PIN Cocktail for Evaluation of Atypical Background: Undifferentiated endometrial sarcoma (UES) is the current designation Small Acinar Proliferations (ASAP) of Prostate for tumors formerly considered as high-grade endometrial stromal sarcoma (ESS). EE Chang, DJ Luthringer, M de Peralta-Venturina, MB Amin. Cedars-Sinai Medical Some UES exhibit uniform nuclear features (UES-U) whereas others exhibit nuclear Center, Los Angeles, CA. pleomorphism (UES-P). We recently identifiedYWHAE-FAM22 genetic rearrangement Background: High correlation with prostate cancer (PCa) potentiates ERG as an in tumors diagnosed as UES or high-grade ESS. YWHAE-FAM22 tumors are clinically additional marker to the PIN cocktail in determining ASAP versus PCa diagnosis. more aggressive than low-grade ESS with JAZF1-SUZ12 genetic rearrangement, but ERG is positive in 11-16% of atypical biopsies, but previous studies do not directly it is yet unclear whether YWHAE-FAM22 tumors differ in clinical course from UES address the added diagnostic value of ERG to the PIN cocktail. This study determines lacking YWHAE-FAM22. the impact of ERG on the final diagnosis beyond assessment based on H&E and PIN Design: We employed YWHAE-FAM22 split-apart fluorescence in situ hybridization cocktail (HE+PIN). and RT-PCR assays to genetically classify 50 UES/high-grade ESS as YWHAE-FAM22 Design: Biopsies from 7/2010-5/2012 diagnosed as ASAP after HE+PIN (PINATYP ESS vs. YWHAE-FAM22-negative UES (UES-U and UES-P). excluded) were stained retrospectively with ERG(EPR3864). All cores with ASAP by Results: Of the 50 tumors, 12 showed appreciable nuclear pleomorphism at 40x H&E received from 6/2012-9/2012 were evaluated with PIN cocktail and ERG results. magnification (UES-P) and none of these hadYWHAE-FAM22 rearrangement. Among Subsequently, all ERG-positive cases from both arms were independently reviewed by the 38 tumors with uniform nuclear features, 24 had YWHAE-FAM22 rearrangement 3 urologic pathologists to render diagnostic impression based on H&E only, HE+PIN, (YWHAE-FAM22 ESS), including 12 with focal low-grade component that mimicked and HE+PIN+ERG evaluation. A negative ERG result is non-contributory. classic low-grade ESS. The remaining 14 cases with uniform nuclear features lacked Results: In the 107 retrospective cases, ERG was negative in 97. Of the 10(9%) ERG- apparent YWHAE-FAM22 rearrangement (UES-U). The clinical features are shown in positive cases, 3 cases by majority and 1 unanimously were upgraded from ASAP to Table 1 with the result of Kaplan-Meier analysis shown in Figure 1. PCa based on HE+PIN evaluation given absent basal cells and variably upregulated Table 1 racemase. After HE+PIN+ERG, 1 case was upgraded to PCa based on ERG staining YWHAE-FAM22 UES-U UES-P while 5 remained ASAP: 4 due to presence of rare basal cells despite increased racemase, Age (average +/- SE) 46 +/- 3 55 +/-5 60 +/-3 1 considered insufficient malignant histology by majority. In the prospective arm, ERG FIGO (1988) stage was positive in 3/24(13%). After HE+PIN, converted diagnoses were 13(54%) PCa 1 6 (27%) 5 (42%) 5 (45%) and 5(21%) benign. One PCa was ERG-positive; benign cases were all ERG-negative. 2-4 16 (73%) 7 (58%) 6 (55%) Follow-up (with >1 year) Of the remaining 7(29%) ASAP cases, 2 were positive for ERG: 1 was converted to Died of disease 6 (32%) 7 (58%) 8 (80%) PCa, the other remained ASAP due to weak inconsistent staining in suspicious glands Alive with disease 8 (42%) 2 (17%) 0 and weak positivity in morphologically benign glands. In total, ERG was positive Alive with no disease 5 (26%) 3 (25%) 2 (20%) in 10%(13/131) of ASAPs; ERG impacted the diagnosis in 1.5%(2/131) of ASAPs. Adjuvant therapy Conclusions: The difficulty in achieving unanimous consensus diagnosis highlights the Chemotherapy and/or radiation 12 (75%) 11 (84%) 10 (91%) None 4 (25%) 2 (16%) 1 (9%) 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. Gynecologic & Obstetrics 1095 Mitotically Active Microglandular Hyperplasia of the Cervix: Absence of K-Ras Mutation and Implications for Differential Diagnosis R Abi-Raad, A Alomari, P Hui, N Buza. Yale University School of Medicine, New Haven, CT. Background: Microglandular hyperplasia (MGH) of the cervix is a benign lesion characterized by proliferation of tightly packed endocervical glands with relatively uniform nuclei and rare to absent mitoses. Endometrioid endometrial adenocarcinomas (EAC) with a microglandular pattern can closely mimic MGH of the cervix resulting in a significant diagnostic dilemma, especially when present in the endocervical curettage. Significant nuclear atypia and increased mitotic activity (>1 mitosis/10 high power field (HPF)) are generally considered to be in favor of EAC. Design: The aim of this study was to review the morphologic features of MGH with special focus on mitotic activity and nuclear atypia in correlation with K-ras mutation analysis. A total of 380 cases of MGH were identified in our departmental archives between January 2005 and June 2012. Of those, 68 were identified in endocervical polyps, which were subjected to an initial screening to further select the final study Conclusions: Due to the high-grade nuclear features present, YWHAE-FAM22 ESS population of 45 cases with extensive MGH arising in endocervical polyps. All available is frequently classified as UES. Our findings suggest that YWHAE-FAM22 ESS is slides were reviewed by two gynecologic pathologists and the mitotic activity and associated with a better prognosis than UES and it is therefore important to distinguish degree of nuclear atypia were evaluated. Ten cases with increased mitotic activity (5 YWHAE-FAM22 ESS from UES. or more mitoses/ 10 HPF) were subjected to K-ras mutation analysis by single-strand conformation polymorphism. Clinical history and follow-up data were retrieved from the patients’ electronic medical records. For a control group, we identified 10 cases of EAC 264A ANNUAL MEETING ABSTRACTS 1097 Correlation and Prognostic Significance of Mismatch Repair Table2: Multivariate analysis of biomarkers in VSCC (MMR) Protein and ARID1A Gene Expression in Endometrial Carcinomas Feature OS PFS (ECs) HR p HR p HPV histo 0.65 0.25 0.54 0.044 G Allo, S Kalloger, A Pollett, M Bernardini, B Clarke. University of Toronto, Toronto, p16+ 0.59 0.14 0.46 0.015 Canada; Toronto General Hospital, Toronto, Canada; Mount Sinai Hospital, Toronto, p53 abnormal 0.84 0.58 0.8 0.4 Canada; Princess Margaret Hospital, Toronto, Canada; University of British Columbia, HPV DNA CISH+ 0.23 0.045 0.33 0.061 Vancouver, Canada.
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