Prognostic determinants in patients with uterine and ovarian clear carcinoma

Rauh‐Hain, J. Alejandro; Winograd, Dina; Growdon, W.B.; Schorge, John O.; A, Goodman; Boruta, David M.; Horowitz, Noya; Carmen, Marcela del

doi:10.1016/j.ygyno.2011.12.221

Cited by 5 publications

(9 citation statements)

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“…They found lower CDC42 mRNA in OCCCs compared to the high-grade serous subtype (50), although our observations indicated the converse—higher CDC42 levels in OCCC than in the EM and high-grade serous subtypes. The discrepancy may be due to differences in stage between the two studies, with the majority of tumors in the present study being stage I, whereas the tumors in the study by Canet et al were primarily stage III and IV (8, 9). However, our findings correlate well with CDC42 and RhoB expression levels found in the Ovarian cancer database of Cancer Science Institute Singapore (CSIOVDB), reporting significantly higher CDC42 and RhoB levels in OCCC compared to the other subtypes (51).…”

Section: Discussioncontrasting

confidence: 79%

“…They are considered type 1 tumors, arising gradually through progression from benign precursors associated with endometriosis, and eventually developing into invasive carcinomas (6, 7). Although often diagnosed in early stages, and with a younger median age at diagnosis compared to, e.g., high-grade serous ovarian carcinomas, stage III–IV OCCC confers an inferior prognosis relative to stage-matched serous tumors (8, 9). The outcome for patients with OCCC, regardless of stage, is also worse than for patients with EM ovarian cancer (10).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

et al. 2017

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ObjectiveOvarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30–50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome.MethodsGene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2). Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3) was used for validation by immunohistochemistry and chromogenic in situ hybridization.ResultsGene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors.ConclusionOCCCs appear genetically heterogeneous, but harbor frequent alterations in chromatin remodeling genes. Overexpression of TFAP2A and ERBB2 was observed on the mRNA level in relation to other ovarian cancer subtypes. However, overexpression of ERBB2 was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct biological features of OCCC discovered here may provide a basis for novel targeted treatment strategies.

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Section: Discussioncontrasting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

et al. 2017

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“…It has been previously reported that 70-90% of tumor-related deaths occurred within 18 months after diagnosis (2,12). However, a recent study reported that the prognosis of uterine carcinosacomas had improved, with an overall median survival of 39 months (13).…”

Section: Discussionmentioning

confidence: 98%

Carcinosarcoma of the uterus: A case report

Adachi

Nonogaki

Minamiguchi

et al. 2016

Molecular and Clinical Oncology

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Abstract. Carcinosarcoma is a rare malignant tumor of the uterus with a poor prognosis. We herein present a case of uterine carcinosarcoma in a 67-year-old woman suffering from pervaginal bleeding for 3 months, with progressive anemia. Upon biopsy of the endometrium, the tumor was diagnosed as endometrioid adenocarcinoma. Total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection were performed. The histological examination revealed that the tumor consisted of serous adenocarcinoma and sarcoma of homologous components. After the operation, chemotherapy with paclitaxel and carboplatin was administered. At approximately 3 years postoperatively, the patient remains alive and recurrence-free.

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“…In contrast to type I cancers, type II endometrial tumors are high-grade (grades 2-3) with a spectrum of histologies, including uterine serous carcinoma (USC), carcinosarcoma, and clear cell carcinoma [3,6,7].These cancers typically (40%-50%) present with disease outside the uterus (stage III or IV) and have a high propensity to recur after primary therapy. Common sites of metastasis include pelvic or para-aortic lymph nodes, the vagina, lungs, liver, and peritoneum, although spread to the brain, bones, and distant lymph nodes has been reported [3,8,9]. Unlike type I EnCa, upfront treatment of type II tumors frequently requires multimodality therapy, combining aggressive cytoreductive surgery to remove visible tumor, platinum-containing chemotherapy, and pelvic or abdominal radiation [10,11].While type II cancers account for only 15%-25% of all EnCa, these tumors are responsible for 75% of the mortality observed, likely related to their higher grade and stage at presentation [3].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer

et al. 2015

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Endometrial cancer is the most common gynecologic cancer in the United States, diagnosed in more than 50,000 women annually.While the majority of women present with low-grade tumors that are cured with surgery and adjuvant radiotherapy, a significant subset of women experience recurrence and do not survive their disease. A disproportionate number of the more than 8,000 annual deaths attributed to endometrial cancer are due to high-grade uterine cancers, highlighting the need for new therapies that target molecular alterations specific to this subset of tumors. Numerous correlative scientific investigations have demonstrated that the HER2 (ERBB2) gene is amplified in 17%-33% of carcinosarcoma, uterine serous carcinoma, and a subset of high-grade endometrioid endometrial tumors. In breast cancer, this potent signature has directed women to anti-HER2-targeted therapies such as trastuzumab and lapatinib. In contrast to breast cancer, therapy with trastuzumab alone revealed no responses in women with recurrent HER2 overexpressing endometrial cancer, suggesting that these tumors may possess acquired or innate trastuzumab resistance mechanisms. This review explores the literature surrounding HER2 expression in endometrial cancer, focusing on trastuzumab and other anti-HER2 therapy and resistance mechanisms characterized in breast cancer but germane to endometrial tumors. Understanding resistance pathways will suggest combination therapies that target both HER2 and key oncogenic escape pathways in endometrial cancer. The Oncologist 2015; 20:1058-1068Implications for Practice: This review summarizes the role of HER2 in endometrial cancer, with a focus on uterine serous carcinoma. The limitations to date of anti-HER2 therapy in this disease site are examined, and mechanisms of drug resistance are outlined based on the experience in breast cancer. Potential opportunities to overcome inherent resistance to anti-HER2 therapy in endometrial cancer are detailed, offering opportunities for further clinical study with the goal to improve outcomes in this challenging disease.

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Prognostic determinants in patients with uterine and ovarian clear carcinoma

Cited by 5 publications

References 0 publications

Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

Carcinosarcoma of the uterus: A case report

The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer

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