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George L. Mutter - One of the best experts on this subject based on the ideXlab platform.

  • REPORTS Altered PTEN Expression as a Diagnostic Marker for the Earliest Endometrial
    2015
    Co-Authors: George L. Mutter, Jan P. A. Baak, Ming-chieh Lin, Jeffrey T. Fitzgerald, Jennifer B, Jacqueline A, Liang-ping Weng, Charis Eng
    Abstract:

    Background: PTEN tumor suppressor gene mutations are the most frequent genetic lesions in Endometrial adeno-carcinomas of the endometrioid sub-type. Testing the hypothesis that al-tered PTEN function precedes the appearance of Endometrial adenocarci-noma has been difficult, however, partly because of uncertainties in pre-cancer diagnosis. Methods: Two series of Endometrial cancer and precancer (Endometrial Intraepithelial Neoplasia, as diagnosed by computerized morpho-metric analysis) tissue samples were studied, one for PTEN mutations by th

  • Endometrial Intraepithelial Neoplasia with secretory differentiation: diagnostic features and underlying mechanisms
    Modern Pathology, 2013
    Co-Authors: Carlos E Parra-herran, Nicolas M Monte, George L. Mutter
    Abstract:

    Endometrial Intraepithelial Neoplasia (EIN) with secretory differentiation and ordinary EIN occurring in a secretory context are rare but recognized findings. We determined how often secretory differentiation in EIN was associated with evidence of circulating progestins in the background endometrium, and studied clinical characteristics and clinical outcomes of affected patients. We selected 41 patients with secretory differentiation in either the EIN itself ( n =31) and/or background endometrium ( n =38). Most (90%, 28/31) secretory EINs were associated with circulating progestins. Rare exceptions were observed, suggesting that secretory EIN may occur as a hormone-independent phenomenon. Circulating progestins are not sufficient, however, to induce EIN secretory differentiation, as 26% (10/38) of EIN within a secretory background were of the ordinary (non-secretory) type. EIN patients with secretory endometrium in the background are younger (averaging 45 years) than the aggregate group of all patients with EIN (53 years in previously published studies) and are often premenopausal with a cyclical source of endogenous progestins. Involution of EIN during follow-up was more frequent (81%, 17/21) for those with a secretory background at the time of initial EIN diagnosis compared with historical averages (25%, 36/142). These results suggest a potential role for endogenous progesterone, as well as therapeutic progestins, in modulating EIN outcomes.

  • Management of Endometrial Precancers
    Obstetrics & Gynecology, 2012
    Co-Authors: Cornelia L. Trimble, Richard J. Zaino, Olga B. Ioffe, Michael Method, Mario M. Leitao, Moss Hampton, Robert V. Higgins, George L. Mutter
    Abstract:

    In the United States, Endometrial cancer is the most commonly diagnosed cancer of the female reproductive system. Strategies to sensitively and accurately diagnose premalignant Endometrial lesions are sorely needed. We reviewed studies pertaining to the diagnostic challenges of Endometrial precancers, their predictive value, and evidence to support management strategies. Currently, two diagnostic schemas are in use: the four-class 1994 World Health Organization hyperplasia system, based on morphologic features of architectural complexity and nuclear atypia and, more recently, the two-class Endometrial Intraepithelial Neoplasia system, which is quantitative. Diagnosis should use criteria and terminology that distinguish between clinicopathologic entities that can be managed differently. In some instances, such as for women with hereditary nonpolyposis colon cancer, biomarkers may aid in diagnosis, but the clinical utility of biomarkers has yet to be determined. Total hysterectomy is curative for atypical Endometrial hyperplasia or Endometrial Intraepithelial Neoplasia, and provides a definitive standard for assessment of a concurrent carcinoma, when clinically appropriate. If hysterectomy is performed for atypical Endometrial hyperplasia or Endometrial Intraepithelial Neoplasia, then intraoperative assessment of the uterine specimen for occult carcinoma is desirable, but optional. Nonsurgical management may be appropriate for patients who wish to preserve fertility or those for whom surgery is not a viable option. Treatment with progestin therapy may provide a safe alternative to hysterectomy; however, clinical trials of hormonal therapies for atypical Endometrial hyperplasia or Endometrial Intraepithelial Neoplasia have not yet established a standard regimen. Future studies will need to determine the optimal nonsurgical management of atypical Endometrial hyperplasia or Endometrial Intraepithelial Neoplasia, standardizing agent, dose, schedule, clinical outcomes, and appropriate follow-up.

  • utility of pax2 as a marker for diagnosis of Endometrial Intraepithelial Neoplasia
    American Journal of Clinical Pathology, 2012
    Co-Authors: Charles M. Quick, Anna R Laury, Nicolas M Monte, George L. Mutter
    Abstract:

    Diagnosis of Endometrial Intraepithelial Neoplasia (EIN) requires learning new criteria. Two trainees rendered diagnoses based on biopsy findings, and then measured the effect of reviewing PAX2 on their interpretation. Fifty-two Endometrial biopsy specimens diagnosed as having EIN were evaluated using EIN criteria. Background Endometrial pattern, altered differentiation, and any features complicating diagnosis were noted. PAX2 stains were scored as confusing, helpful, or noncontributory. Fifty-two cases generated 104 passes; 82% were rediagnosed as EIN. The diagnosis was complicated because of altered differentiation (14%), EIN and background separation (13%), large lesions lacking background (11%), and secretory background (8%). PAX2 was most helpful in cases with secretory backgrounds and when EIN lacked adjacent normal tissue, and most confusing when scoring was ambiguous (14%). The diagnosis of EIN can be difficult when: (1) the lesion cannot be easily compared with background; (2) there is a confounding process; and (3) gland differentiation is altered. PAX2 can be of assistance in delimiting EIN lesions.

  • Utility of PAX2 as a Marker for Diagnosis of Endometrial Intraepithelial Neoplasia
    American Journal of Clinical Pathology, 2012
    Co-Authors: Charles M. Quick, Anna R Laury, Nicolas M Monte, George L. Mutter
    Abstract:

    Diagnosis of Endometrial Intraepithelial Neoplasia (EIN) requires learning new criteria. Two trainees rendered diagnoses based on biopsy findings, and then measured the effect of reviewing PAX2 on their interpretation. Fifty-two Endometrial biopsy specimens diagnosed as having EIN were evaluated using EIN criteria. Background Endometrial pattern, altered differentiation, and any features complicating diagnosis were noted. PAX2 stains were scored as confusing, helpful, or noncontributory. Fifty-two cases generated 104 passes; 82% were rediagnosed as EIN. The diagnosis was complicated because of altered differentiation (14%), EIN and background separation (13%), large lesions lacking background (11%), and secretory background (8%). PAX2 was most helpful in cases with secretory backgrounds and when EIN lacked adjacent normal tissue, and most confusing when scoring was ambiguous (14%). The diagnosis of EIN can be difficult when: (1) the lesion cannot be easily compared with background; (2) there is a confounding process; and (3) gland differentiation is altered. PAX2 can be of assistance in delimiting EIN lesions.

Petra M. Casey - One of the best experts on this subject based on the ideXlab platform.

  • oral progestogens versus levonorgestrel releasing intrauterine system for treatment of Endometrial Intraepithelial Neoplasia
    Journal of Womens Health, 2017
    Co-Authors: Mary L. Marnach, Kristina A. Butler, Michael R. Henry, Catherine E. Hutz, Carrie L. Langstraat, Christine M. Lohse, Petra M. Casey
    Abstract:

    Abstract Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of Endometrial reassessment for women with Endometrial Intraepithelial Neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p < 0.001). Among 332 women with follow-up Endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometria...

  • Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia*
    Journal of Womens Health, 2016
    Co-Authors: Mary L. Marnach, Kristina A. Butler, Michael R. Henry, Catherine E. Hutz, Carrie L. Langstraat, Christine M. Lohse, Petra M. Casey
    Abstract:

    Abstract Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of Endometrial reassessment for women with Endometrial Intraepithelial Neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p 

Mary L. Marnach - One of the best experts on this subject based on the ideXlab platform.

  • oral progestogens versus levonorgestrel releasing intrauterine system for treatment of Endometrial Intraepithelial Neoplasia
    Journal of Womens Health, 2017
    Co-Authors: Mary L. Marnach, Kristina A. Butler, Michael R. Henry, Catherine E. Hutz, Carrie L. Langstraat, Christine M. Lohse, Petra M. Casey
    Abstract:

    Abstract Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of Endometrial reassessment for women with Endometrial Intraepithelial Neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p < 0.001). Among 332 women with follow-up Endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometria...

  • Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia*
    Journal of Womens Health, 2016
    Co-Authors: Mary L. Marnach, Kristina A. Butler, Michael R. Henry, Catherine E. Hutz, Carrie L. Langstraat, Christine M. Lohse, Petra M. Casey
    Abstract:

    Abstract Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of Endometrial reassessment for women with Endometrial Intraepithelial Neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p 

Alp Usubutun - One of the best experts on this subject based on the ideXlab platform.

  • The Role of Frozen-Section in the Surgical Management of Patients with Endometrial Intraepithelial Neoplasia.
    Türk Patoloji Dergisi, 2015
    Co-Authors: Mehmet Coskun Salman, Alp Usubutun, Derman Basaran, Nejat Ozgul, Kunter Yuce
    Abstract:

    OBJECTIVE Patients with Endometrial Intraepithelial Neoplasia may have concurrent Endometrial cancer if managed surgically or develop cancer in time if managed conservatively. Therefore, intraoperative assessment of the uterus may be helpful if a surgical approach is decided on. Our study aimed to investigate the role of frozen-section examination in patients with Endometrial Intraepithelial Neoplasia. MATERIAL AND METHOD Patients with Endometrial Intraepithelial Neoplasia who were subjected to hysterectomy with intraoperative frozen-section assessment were included. Main outcome measures were the rates of concurrent Endometrial cancer and concurrent high-risk Endometrial cancer as well as the efficacy of frozen-section in the detection of concurrent invasive disease and in the designation of low-risk and high-risk features. RESULTS The study group consisted of seventy-three patients. Permanent pathology revealed Endometrial adenocarcinoma in 19.2% whereas only one patient (1.4%) had high-risk disease necessitating surgical staging. Frozen-section diagnoses were consistent with final pathology in 93.2% of patients in terms of the presence or absence of co-existent carcinoma. When frozen-section reports were further evaluated in terms of the presence or absence of high-risk Endometrial carcinoma, consistency with the final pathology was seen in 98.6% of patients. CONCLUSION Co-existent Endometrial cancer is not uncommon in Endometrial Intraepithelial Neoplasia. Intraoperative frozen-section evaluation should therefore be considered whenever possible. Frozen-section is effective in the detection of coexistent invasive disease and in the designation of low-risk features. Although coexistent high-risk cancer is extremely rare, frozen-section assessment is not successful in determining high-risk features. Therefore, a re-staging surgery may be required on rare occasions.

  • Reproducibility of Endometrial Intraepithelial Neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists
    Modern Pathology, 2012
    Co-Authors: Alp Usubutun, George L. Mutter, Arzu Saglam, Anil Dolgun, Eylem Akar Özkan, Aytekin Akyol, H Dilek Bulbul, Zerrin Calay, Tan Ince, Funda Eren
    Abstract:

    Endometrial Intraepithelial Neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal Endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for Endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two Endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as Endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

  • Reproducibility of Endometrial Intraepithelial Neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists
    Modern Pathology, 2012
    Co-Authors: Alp Usubutun, George L. Mutter, Arzu Saglam, Anil Dolgun, Eylem Akar Özkan, Tan A. Ince, Aytekin Akyol, H Dilek Bulbul, Zerrin Calay, Funda Eren
    Abstract:

    Reproducibility of Endometrial Intraepithelial Neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists

  • the selective expression of ret finger protein in Endometrial cancer can rfp be a marker of serous carcinomas
    Türk Patoloji Dergisi, 2012
    Co-Authors: Gaye Guler Tezel, Zehra Ordulu, Cigdem Himmetoglu, Alp Usubutun
    Abstract:

    OBJECTIVE: Endometrial cancer is a common malignancy of the gynecological system and has been classified into two major groups, Types I and II. Type I tumors are estrogen-related, low-grade endometrioid tumors, whereas type II tumors are aggressive, high-grade non-endometrioid tumors. Ret finger protein is a nuclear transcription factor with a tripartite motif that is highly expressed in different tumor cells. MATERIAL AND METHOD: To analyze the expression of ret finger protein in Endometrial tissues and cancer, 18 cases of secretory and proliferative endometrium, Endometrial polyp, Endometrial hyperplasia and Endometrial Intraepithelial Neoplasia and 21 cases of types I and II Endometrial carcinoma were evaluated immunohistochemically. RESULTS: Although rare cases of secretory endometrium showed a weak focal nuclear positivity, remaining proliferative endometrium, Endometrial hyperplasia and type I endometrioid cancer cases were negative. In contrast, all cases of serous cancers showed strong nuclear positivity. After these strong positive results for serous Endometrial cancer, 12 more cases of ovarian and Endometrial serous carcinoma cases were added to the study. All of the additional cases were also strongly positive for ret finger protein. CONCLUSION: We suggest that ret finger protein might play a role in the carcinogenesis of the serous tumors of gynecological system and can be used to differentiate serous carcinomas from other epithelial tumors.

  • Comparison of WHO and Endometrial Intraepithelial Neoplasia classifications in predicting the presence of coexistent malignancy in Endometrial hyperplasia.
    Journal of Gynecologic Oncology, 2010
    Co-Authors: Mehmet Coskun Salman, Alp Usubutun, K. Boynukalin, Kunter Yuce
    Abstract:

    1 Objective: The most commonly used classification system for Endometrial hyperplasia is the World Health Organi- zation system which is based on subjective criteria. Another classification system is Endometrial Intraepithelial Neoplasia (EIN) system which uses diagnostic criteria including cytological demarcation, crowded gland architecture, minimum size of 1 mm, and careful exclusion of mimics, and aims to identify a precancer or cancer. The objective of this study was to compare the two classification systems in terms of predicting the presence of a coexistent cancer in surgically treated patients. Methods: Biopsy and hysterectomy specimens of 49 women who were subjected to surgery with a preoperative diagnosis of Endometrial hyperplasia (EH) according to the WHO system were re-evaluated retrospectively by using EIN system. Results: Among the 49 patients, 69.4% had complex atypical EH and 75.5% had EIN at biopsy specimens. EIN was detected in 94.1% of complex atypical EH, and 41.7% of non-atypical EH. Nine women (18.4%) had Endometrial cancer. Among women with cancer, all had complex atypical EH or EIN. The rate of coexistent Endometrial cancer was 26.5% in women with complex atypical EH and 24.3% in women with EIN. Conclusion: Diagnoses of atypical or complex atypical EH and EIN had similar sensitivities and negative predictive values in predicting the coexistent Endometrial cancer. Either of these two classification systems may be used safely when an experienced pathologist is available. However, use of the objective EIN system may be preferred whenever possible to prevent diagnostic errors in centers where an experienced pathologist is not available.

Kristina A. Butler - One of the best experts on this subject based on the ideXlab platform.

  • oral progestogens versus levonorgestrel releasing intrauterine system for treatment of Endometrial Intraepithelial Neoplasia
    Journal of Womens Health, 2017
    Co-Authors: Mary L. Marnach, Kristina A. Butler, Michael R. Henry, Catherine E. Hutz, Carrie L. Langstraat, Christine M. Lohse, Petra M. Casey
    Abstract:

    Abstract Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of Endometrial reassessment for women with Endometrial Intraepithelial Neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p < 0.001). Among 332 women with follow-up Endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometria...

  • Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia*
    Journal of Womens Health, 2016
    Co-Authors: Mary L. Marnach, Kristina A. Butler, Michael R. Henry, Catherine E. Hutz, Carrie L. Langstraat, Christine M. Lohse, Petra M. Casey
    Abstract:

    Abstract Background: Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of Endometrial reassessment for women with Endometrial Intraepithelial Neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. Methods: We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Results: Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m2 vs. 31 kg/m2; p