cyclin-d1 has been researched along with Sarcoma--Endometrial-Stromal* in 8 studies
8 other study(ies) available for cyclin-d1 and Sarcoma--Endometrial-Stromal
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Uterine Endometrial Stromal Tumors With Pure Low-Grade Morphology Harboring YWHAE::NUTM2 Fusions: Report of a Case Series Emphasizing Potential for High-Grade Transformation and Aggressive Behavior.
Uterine endometrial stromal sarcomas (ESS) with YWHAE::NUTM2 gene fusions are typically morphologically high-grade tumors composed of atypical round cells, sometimes associated with a low-grade fibromyxoid component; they are currently included in the category of high-grade ESS (HGESS). We report 5 morphologically pure low-grade endometrial stromal tumors harboring YWHAE::NUTM2 fusions, including 1 endometrial stromal nodule (ESN) and 4 low-grade endometrial stromal sarcomas (LGESS), an association only occasionally reported previously. Patients ranged from 30 to 51 (mean=43) years and tumors from 4.5 to 7.5 cm (mean=5.7). All were stage I at diagnosis (confined to the uterus). Microscopically, the 4 LGESS showed extensive "tongue-like" invasion of the myometrium, and the ESN was entirely confined to the endometrium with no myometrial invasion. All tumors were composed entirely of morphologically uniform bland ovoid cells resembling proliferative endometrial stroma. A fibromyxoid component was seen in 1 LGESS and the ESN; in the LGESS, this was the sole component. Atypical round cells characteristic of YWHAE::NUTM2 HGESS were not identified. Mitotic count ranged from <1 to 13 per 10 high-power fields (mean: 3). CD10 was positive in 2/4 (focal), estrogen receptor in 5/5 (focal=1; diffuse=4), progesterone receptor in 5/5 (focal=1; diffuse=4) and cyclin D1 was diffusely positive in 3/4. Follow-up was available in all 5 patients and ranged from 6 to 159 months (mean=72). Two patients with LGESS had recurrent disease at 15 and 155 months; 1 showed predominantly LGESS with rare round cells in the initial recurrence and pure HGESS in a subsequent recurrence, while the other patient's recurrent tumor was predominantly HGESS (90%) in a background of focal fibromyxoid LGESS (10%). Both patients rapidly progressed and died of disease within 5 months of high-grade recurrence. We show that rare cases of morphologically pure low-grade endometrial stromal tumors, some but not all with a fibromyxoid component, harbor YWHAE::NUTM2 fusions and may recur rapidly, with transformation to HGESS and aggressive behavior. Our findings suggest that at least a subset of YWHAE::NUTM2 HGESS evolves from LGESS. We suggest that cyclin D1 and CD10 staining should be performed in all LGESS. Diffuse staining for cyclin D1 and/or negative or focal staining for CD10 should suggest the possibility of a YWHAE::NUTM2 fusion, and appropriate molecular testing should be undertaken. Since no sing Topics: 14-3-3 Proteins; Biomarkers, Tumor; Cyclin D1; Endometrial Neoplasms; Endometrial Stromal Tumors; Endometrium; Female; Humans; Neoplasm Recurrence, Local; Sarcoma, Endometrial Stromal; Uterine Neoplasms | 2023 |
BCOR Internal Tandem Duplication Associated Uterine Sarcoma: Expanding the Clinicopathologic Spectrum.
The diagnosis of high-grade endometrial stromal sarcoma has become more refined following molecular characterization of these tumors. Recently BCOR internal tandem duplications (ITD) have been identified in a small number of high-grade endometrial stromal sarcoma. Here we present an additional case of this rare entity in a young woman in her late teens. She presented with menorrhagia and underwent resection of 2 uterine lesions. The tumor was a spindle cell neoplasm composed of long fascicles with low to moderate cellularity, mild to moderate cytologic atypia, and up to 2 mitotic figures per 10 high power fields. Necrosis was not identified. Immunohistochemical stains showed the tumor to be positive for cyclin D1 in >50% of tumor cells, focally positive for CD10, and negative for SMA, desmin, h-caldesmon, and ALK1. BCOR ITD was confirmed by polymerase chain reaction with subsequent Sanger sequencing. Clues to the diagnosis of BCOR ITD uterine sarcoma include young patient age, uniform nuclear features, and diffuse positivity for cyclin D1. These features should prompt further molecular interrogation for definitive diagnosis, which is important for prognostication. Topics: Adolescent; Biomarkers, Tumor; Cyclin D1; Endometrial Neoplasms; Female; Humans; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma, Endometrial Stromal; Uterine Neoplasms | 2022 |
Immunohistochemical Expression of Different Subtypes of Cytokeratins by Endometrial Stromal Sarcoma.
Endometrial stromal sarcomas (ESS) are rare and understudied gynecologic mesenchymal neoplasms. These tumors can be confused with many other gynecologic and nongynecologic tumors due to their variegated morphologic appearance and nonspecific immunohistochemical profile. ESS can express cytokeratin (CK) and, therefore, may be misdiagnosed as carcinoma especially in extrauterine locations and when recurrence/metastasis is present. In this study, we investigated the expression of a wide spectrum of CKs consisting of AE1/3, CAM 5.2, HMCK, MNF116, CK5, CK6, CK7, CK8/18, CK14, CK17, CK19, and CK20 in 6 low-grade and 5 high-grade ESS. In addition, staining for estrogen receptor, progesterone receptor, CD10, and cyclin D1 was performed. Our results showed that CKs AE1/3, CAM 5.2, MNF116, and CK8/18 are more expressed in low-grade ESS, whereas high-grade ESS express more AE1/3 and CAM 5.2. In problematic cases, especially in recurrences or metastases, the immunohistochemical panel of antibodies AE1/3, MNF116, CAM 5.2, and CK8/18, together with other classic immunohistochemical markers CD10, cyclin D1, estrogen receptor, and progesterone receptor, may be helpful in the differential diagnosis between ESS and other gynecologic and nongynecologic malignancies. Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cyclin D1; Diagnosis, Differential; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Middle Aged; Neprilysin; Receptors, Estrogen; Receptors, Progesterone; Sarcoma, Endometrial Stromal | 2019 |
[Endometrial stromal sarcoma: morphologic features and detection of JAZF1-SUZ12 and YWHAE FAM22 fusion genes].
To study the morphologic features, immunophenotype and significance of expression of JAZF1-SUZ12 and YWHAE-FAM22 fusion genes in endometrial stromal sarcoma (ESS).. Fifty-three cases of ESS were retrieved and the pathologic features were reviewed. Immunohistochemical study for estrogen receptor, progesterone receptor, CD10, cyclin D1, smooth muscle actin, desmin and H-caldesmon were carried out using tissue microarray technology. Reverse transcription-polymerase chain reaction (RT-PCR) was applied for detection of expression of JAZF1-SUZ12 and YWHAE-FAM22 fusion genes in 47 cases of ESS and 12 cases of other spindle cell neoplasia in uterus (including 2 cases of undifferentiated sarcoma, 3 cases of leiomyosarcoma, 3 cases of leiomyoma, 4 cases of adenosarcoma and 2 cases of uterine tumor resembling ovarian sex cord tumor).. The 53 cases of ESS studied included 43 cases of low-grade ESS and 10 cases of high-grade ESS. As for low-grade ESS, in addition to the classic morphologic features, smooth muscle differentiation was present in 7 cases (16.3%), sex cord-like differentiation in 2 cases (4.7%), rhabdoid differentiation in 1 case (2.3%), clear cell changes in 1 case (2.3%) and schwannoma-like palisading pattern in 1 case (2.3%). As for high-grade ESS, sex cord-like differentiation (1 case), mucinous microcystic changes (1 case) and focal clear cell changes (1 case) were also observed. The expression rate of estrogen receptor, progesterone receptor, CD10, cyclin D1, smooth muscle actin, desmin and H-caldesmon was 86.0%, 81.4%, 74.4%, 2.3%, 23.3%, 23.3% and 4.7% in low-grade ESS, respectively, and was 1/10, 6/10, 6/10, 7/10, 1/10, 1/10 and 0 in high-grade ESS, respectively. RNA extraction was successful in 47 cases of ESS, including 39 cases of low-grade ESS and 8 cases of high-grade ESS. The positive rate of JAZF1-SUZ12 fusion gene was 30.8% (12/39) in low-grade ESS. The positive rate of YWHAE-FAM22 fusion gene was 12.5% (1/8) in high-grade ESS. The 14 control cases were all negative for JAZF1-SUZ12 and YWHAE-FAM22 fusion genes.. As uncommon pathologic pattern may occur in both low-grade ESS and high-grade ESS, detection of JAZF1-SUZ1 and YWHAE-FAM22 fusion genes by RT-PCR would be helpful in diagnosis and differential diagnosis of ESS, especially for those tumors which lack typical morphologic features. Topics: 14-3-3 Proteins; Co-Repressor Proteins; Cyclin D1; DNA-Binding Proteins; Endometrial Neoplasms; Female; Humans; Leiomyosarcoma; Neoplasm Proteins; Polycomb Repressive Complex 2; Recombinant Proteins; Sarcoma, Endometrial Stromal; Tissue Array Analysis; Transcription Factors | 2016 |
Cyclin D1 does not distinguish YWHAE-NUTM2 high-grade endometrial stromal sarcoma from undifferentiated endometrial carcinoma.
Topics: Biomarkers, Tumor; Cyclin D1; Endometrial Neoplasms; Female; Gene Rearrangement; Humans; Oncogene Proteins, Fusion; Sarcoma, Endometrial Stromal | 2015 |
Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement.
Endometrial stromal sarcomas with the YWHAE-NUTM2A/B genetic fusion characteristically contain high-grade round to epithelioid cell component that is strongly and diffusely cyclin D1-positive and it may or may not show an associated low-grade fibroblastic/myxoid cell component. They are clinically more aggressive than endometrial stromal sarcomas with the JAZF1-SUZ12 genetic fusion and frequently demonstrate extrauterine extension at initial clinical presentation. In this setting, the tumor may be misdiagnosed as gastrointestinal stromal tumor. This study examines the expression of KIT and ANO1 in 14 YWHAE-NUTM2A/B tumors by immunohistochemistry. Staining localization was determined as membranous and/or cytoplasmic, and the staining intensity was assessed (negative, weak, moderate and strong). Of the 14 tumors, 6 contained only a high-grade round cell component, 2 only a low-grade fibroblastic component and 6 had both components in the slides evaluated. The high-grade round cell component displayed moderate to strong membranous/cytoplasmic KIT staining in all tumors (12 of 12). The low-grade fibroblastic cell component showed only weak cytoplasmic KIT staining in 3 of 8 tumors. In contrast, ANO1 was negative in all 14 neoplasms, irrespective of the component evaluated. Sanger sequencing analysis (exons 9, 11, 13 and 17) and Ampliseq Cancer Panel mutation screen (Ion Torrent) demonstrated no KIT mutations in three KIT-positive YWHAE-NUTM2A/B tumors. This study shows that the high-grade round cell component of YWHAE-NUTM2A/B endometrial stromal sarcoma consistently expresses KIT but lacks KIT hotspot mutations. KIT expression may represent a potential diagnostic pitfall in the evaluation of YWHAE-NUTM2A/B endometrial stromal sarcoma presenting with pelvic/abdominal mass, particularly in situations where its uterine origin is not definitive, and thus a panel of antibodies that includes ANO1 and cyclin D1 is necessary. Topics: 14-3-3 Proteins; Anoctamin-1; Biomarkers, Tumor; Chloride Channels; Cyclin D1; Endometrial Neoplasms; Female; Gene Rearrangement; Humans; Immunohistochemistry; Mutation; Neoplasm Proteins; Proto-Oncogene Proteins c-kit; Sarcoma, Endometrial Stromal | 2014 |
Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement.
Endometrial stromal sarcoma (ESS) characterized by YWHAE-FAM22 genetic fusion is histologically higher grade and clinically more aggressive than ESS with JAZF1-SUZ12 or equivalent genetic rearrangements, hence it is clinically important to recognize this subset of ESS. To identify diagnostic immunomarkers for this biologically defined ESS subset, we compared gene expression profiles between YWHAE-FAM22 ESS and JAZF1-rearranged ESS. These studies showed consistent upregulation of cyclin D1 in YWHAE-FAM22 ESS compared with JAZF1-SUZ12 ESS. Immunohistochemically, the high-grade round cell component of all 12 YWHAE-FAM22 ESS demonstrated diffuse (≥70%) moderate to strong nuclear cyclin D1 staining, and this diffuse positivity was not seen in 34 ESSs with JAZF1 and equivalent genetic rearrangements or in 21 low-grade ESS with no demonstrable genetic rearrangements. In a series of 243 non-ESS pure uterine mesenchymal and mixed epithelial-mesenchymal tumors, only 2 of 8 undifferentiated endometrial sarcomas with nuclear uniformity and 1 of 80 uterine leiomyosarcomas demonstrate diffuse cyclin D1 immunoreactivity. Both cyclin D1-positive undifferentiated endometrial sarcomas showed diffuse strong CD10 staining, which is consistently absent in the high-grade round cell component of YWHAE-FAM22 ESS. The low-grade spindle cell component of YWHAE-FAM22 ESS showed a spatially heterogenous cyclin D1 staining pattern that was weaker and less diffuse overall. Our findings indicate that cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22 ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS. Topics: Biomarkers, Tumor; Cell Nucleus; Cyclin D1; Endometrial Neoplasms; Female; Gene Rearrangement; Humans; In Situ Hybridization, Fluorescence; Leiomyosarcoma; Neoplasm Proteins; Oncogene Proteins, Fusion; Polycomb Repressive Complex 2; Sarcoma, Endometrial Stromal; Tissue Array Analysis; Transcription Factors; Up-Regulation | 2012 |
Coincident expression of beta-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas.
Aberrant activation of the Wnt signaling pathway has been implicated in tumorigenesis of a wide range of tumors, including colorectal cancer. Regarding endometrial stromal tumors and related high-grade sarcomas, there have been some reports regarding nuclear accumulation of beta-catenin. To clarify the function of the aberrant Wnt signaling pathway in these tumors, we searched for mutations of the CTNNB1 (beta-catenin) gene and APC gene by PCR direct sequencing and analyzed the methylation status of SFRP genes. We also examined overexpression of cyclin D1 and MMP-7, which are direct target genes of beta-catenin. Eight endometrial stromal nodules, 16 low-grade endometrial stromal sarcomas, and 13 undifferentiated endometrial sarcomas were examined. PCR and direct sequencing revealed no mutation of the beta-catenin gene or the APC gene. Concerning the promoter methylation status of SFRP genes, methylation-specific PCR revealed no significant difference between the group with nuclear beta-catenin expression and that without nuclear beta-catenin expression. Immunohistochemistry revealed overexpression of cyclin D1 in 2 out of 8 endometrial stromal nodules, 1 out of 17 low-grade endometrial stromal sarcomas, and 6 out of 13 undifferentiated endometrial sarcomas, and these 6 undifferentiated endometrial sarcomas simultaneously expressed nuclear beta-catenin. Interestingly, all six undifferentiated endometrial sarcoma cases with cyclin D1 overexpression histologically featured rather uniform nuclei. In contrast, the six cases of undifferentiated endometrial sarcoma with highly pleomorphic nuclei were all negative for cyclin D1. In conclusion, among endometrial stromal tumors and related sarcomas, undifferentiated endometrial sarcomas featuring uniform nuclei were characterized by frequent coincident expression of beta-catenin and cyclin D1. This finding raises the possibility that cyclin D1 is upregulated by beta-catenin in these high-grade sarcomas previously called high-grade endometrial stromal sarcoma. Topics: Adult; Aged; Aged, 80 and over; beta Catenin; Biomarkers, Tumor; Cell Nucleus; Co-Repressor Proteins; Cyclin D1; DNA Methylation; DNA Mutational Analysis; DNA-Binding Proteins; Endometrial Neoplasms; Female; Genes, APC; Glycoproteins; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Matrix Metalloproteinase 7; Middle Aged; Mutation; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Endometrial Stromal; Signal Transduction; Transcription Factors; Young Adult | 2010 |