WT1 expression associated with platinum-sensitivity and improved progression-free survival in uterine serous carcinoma

2021 ◽  
Vol 162 ◽  
pp. S337-S338
Author(s):  
Jennifer McEachron ◽  
Nancy Zhou ◽  
Agha Wajdan Baqir ◽  
Absia Jabbar ◽  
Kyra Gassmann ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Free Survival ◽  
Platinum Sensitivity ◽  
Uterine Serous Carcinoma

BRCA1 Immunohistochemical Staining as a Prognostic Indicator in Uterine Serous Carcinoma

2013 ◽  
Vol 23 (1) ◽  
pp. 113-118 ◽  
Author(s):  
James P. Beirne ◽  
Jennifer E. Quinn ◽  
Perry Maxwell ◽  
Steve E. Kalloger ◽  
Jessica McAlpine ◽  
...  
Keyword(s):  
Protein Expression ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
Serous Carcinoma ◽  
Nuclear Staining ◽  
Cell Nuclei ◽  
Brca1 Protein ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
Uterine Serous Carcinoma

ObjectivesThe objective of this study was to investigate the relationship between BRCA1 protein expression, as determined by immunohistochemistry, and clinical outcome in uterine serous carcinoma (USC).MethodsA tissue microarray containing duplicate cores of 73 cases of USC was immunohistochemically stained with mouse anti-BRCA1 (Ab-1) mouse monoclonal (MS110) antibody. The cores were scored in a semiquantitative manner evaluating both the distribution and intensity of nuclear staining. BRCA1 protein expression was correlated with progression-free survival.ResultsSeventy-two of 73 cases were assessable, and there was a statistically significant decreased progression-free survival for those cases exhibiting tumor cell nuclei staining of 76% or greater (P = 0.0023).ConclusionsOur study illustrates that a low level of BRCA1 protein expression is a favorable prognostic indicator in USC, similar to what is observed in high-grade serous ovarian carcinoma. Further studies should focus on the BRCA1 status of USCs at a molecular level and also investigate whether BRCA1 protein expression is associated with response to chemotherapy in USC.

scholarly journals Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu

2018 ◽  
Vol 36 (20) ◽  
pp. 2044-2051 ◽  
Author(s):  
Amanda N. Fader ◽  
Dana M. Roque ◽  
Eric Siegel ◽  
Natalia Buza ◽  
Pei Hui ◽  
...  
Keyword(s):  
Phase Ii Trial ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Randomized Phase Ii ◽  
Control Versus ◽  
Epidermal Growth ◽  
Uterine Serous Carcinoma

Purpose Uterine serous carcinoma is a rare, aggressive variant of endometrial cancer. Trastuzumab is a humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of uterine serous carcinoma. This multicenter, randomized phase II trial compared carboplatin-paclitaxel with and without trastuzumab in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu. Methods Eligible patients had primary stage III or IV or recurrent HER2/neu-positive disease. Participants were randomly assigned to receive carboplatin-paclitaxel (control arm) for six cycles with or without intravenous trastuzumab (experimental arm) until progression or unacceptable toxicity. The primary end point was progression-free survival, which was assessed for differences between treatment arms via one-sided log-rank tests. Results From August 2011 to March 2017, 61 patients were randomly assigned. Forty progression-free survival–related events occurred among 58 evaluable participants. Among all patients, median progression-free survival was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage III or IV disease undergoing primary treatment ( P = .013; HR, 0.40; 90% CI, 0.20 to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among 17 patients with recurrent disease ( P = .003; HR, 0.14; 90% CI, 0.04 to 0.53). Toxicity was not different between treatment arms, and no unexpected safety signals emerged. Conclusion Addition of trastuzumab to carboplatin-paclitaxel was well tolerated and increased progression-free survival. These encouraging results deserve further investigation to determine their impact on overall survival in patients with advanced or recurrent uterine serous carcinoma who overexpress HER2/neu.

scholarly journals High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Katharina Bischof ◽  
Stian Knappskog ◽  
Ingunn Stefansson ◽  
Emmet Martin McCormack ◽  
Jone Trovik ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Expression ◽  
Serous Carcinoma ◽  
Free Survival ◽  
Uterine Serous Carcinoma

scholarly journals Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcinoma

2020 ◽  
Vol 477 (5) ◽  
pp. 677-685
Author(s):  
Ben Davidson ◽  
Arild Holth ◽  
Hiep Phuc Dong
Keyword(s):  
Stem Cell ◽  
Survival Analysis ◽  
Cancer Stem Cell ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
Stem Cell Marker ◽  
Serous Carcinoma ◽  
High Grade ◽  
Poor Survival ◽  
Free Survival

Abstract The objective of the present study was to perform a quantitative analysis of cancer stem cell (CSC) marker expression in ovarian carcinoma effusions. The clinical role of SSEA1 in metastatic high-grade serous carcinoma (HGSC) was additionally analyzed. CD133, Nanog, SOX2, Oct3/4, SSEA1, and SSEA4 protein expressions were quantitatively analyzed using flow cytometry (FCM) in 24 effusions. SSEA1 expression by immunohistochemistry was analyzed in 384 HGSC effusions. Highly variable expression of CSC markers by FCM was observed, ranging from 0 to 78% of Ber-EP4-positive cells in the case of CD133, with the largest number of negative specimens seen for SSEA4. SSEA1 expression by immunohistochemistry was found in HGSC cells in 336/384 (89%) effusions, most commonly focally (< 5% of cells). SSEA1 was overexpressed in post-chemotherapy disease recurrence specimens compared with chemo-naïve HGSC effusions tapped at diagnosis (p = 0.029). In univariate survival analysis, higher SSEA1 expression was significantly associated with poor overall survival (p = 0.047) and progression-free survival (p = 0.018), though it failed to retain its prognostic role in Cox multivariate survival analysis in which it was analyzed with clinical parameters (p = 0.059 and p = 0.111 for overall and progression-free survival, respectively). In conclusion, CSC markers are variably expressed in ovarian carcinoma effusions. SSEA1 expression is associated with disease progression and poor survival in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.

scholarly journals Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution Registry of a Rare Tumor

2015 ◽  
Vol 33 (24) ◽  
pp. 2675-2682 ◽  
Author(s):  
David M. Gershenson ◽  
Diane C. Bodurka ◽  
Karen H. Lu ◽  
Lisa C. Nathan ◽  
Ljiljana Milojevic ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Primary Therapy ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Carcinoma Of The Ovary

Purpose Low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is a rare subtype of ovarian or peritoneal cancer characterized by young age at diagnosis and relative resistance to chemotherapy. The purpose of this study is to report our updated experience with women diagnosed with LGSOC or LGSPC to assess the validity of our original observations. Patients and Methods Eligibility criteria for patients from our database were: stage I to IV LGSOC or LGSPC, original diagnosis before January 2012, and adequate clinical information. All patients were included in progression-free survival, overall survival, and multivariable Cox regression analyses. A subset analysis was performed among patients with stage II to IV low-grade serous carcinoma treated with primary surgery followed by platinum-based chemotherapy. Results We identified 350 eligible patients. Median progression-free survival was 28.1 months; median overall survival was 101.7 months. In the multivariable analysis, compared with women age ≤ 35 years, those diagnosed at age > 35 years had a 43% reduction in likelihood of dying (hazard ratio, 0.53; 95% CI, 0.37 to 0.74; P < .001). Having disease present at completion of primary therapy was associated with a 1.78 increased hazard of dying compared with being clinically disease free (P < .001). Similar trends were noted in the smaller patient cohort. In this cohort, women with LGSPC had a 41% decreased chance of dying (hazard ratio, 0.59; 95% CI, 0.36 to 0.98; P = .04) compared with those with LGSOC. Conclusion Women age < 35 years with low-grade serous carcinoma and those with persistent disease at completion of primary therapy have the worst outcomes. Patients with LGSPC seem to have a better prognosis than those with LGSOC.

Multicenter Clinicopathological Study of High-Grade Serous Carcinoma Presenting as Primary Peritoneal Carcinoma

2018 ◽  
Vol 28 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Shinichi Komiyama ◽  
Yoshihiro Nishijima ◽  
Haruhiro Kondo ◽  
Hiroyuki Nomura ◽  
Satoshi Yamaguchi ◽  
...  
Keyword(s):  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Serous Carcinoma ◽  
Tumor Diameter ◽  
Gynecologic Oncology Group ◽  
High Grade ◽  
Debulking Surgery ◽  
Free Survival ◽  
Primary Debulking Surgery

ObjectiveWe conducted a multicenter clinicopathological study to characterize patients with high-grade serous carcinoma presenting as primary peritoneal carcinoma (clinical PPC).MethodsAt 9 sites in Japan, patients with clinical PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian involvement by high-grade serous carcinoma. There was no systematic detailed histopathological review of the fallopian tubes to determine whether they were involved by serous carcinoma.ResultsThere were 139 patients and 64% were aged 60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL. Pretreatment performance status was poor in more than 50%, endometrial cytology was positive in 40.3%, and the preoperative clinical diagnosis was correct in 72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64% underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). The main tumor sites were the upper abdomen (greater omentum), extrapelvic peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of patients undergoing systematic retroperitoneal node dissection. The optimal surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with postoperative chemotherapy. Median progression-free survival was 19.0 months and median overall survival was 41.0 months. Multivariate analysis showed that prognostic factors for progression-free survival were NAC and residual tumor diameter after debulking surgery, whereas the only prognostic factor for overall survival was the residual tumor diameter.ConclusionsThis study identified various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a reasonable treatment strategy, and complete debulking surgery is optimum.

scholarly journals PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

2021 ◽  
Vol 65 (1) ◽  
Author(s):  
Caroline Eymerit-Morin ◽  
Anna Ilenko ◽  
Thomas Gaillard ◽  
Justine Varinot ◽  
Eva Compérat ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Histological Subtypes ◽  
Free Survival ◽  
Ovarian Cancers ◽  
Cancer Subtype ◽  
Grade 3 ◽  
Subtype A

Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones – QR1 and E1L3N – with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.

A phase II trial of the Wee1 inhibitor adavosertib (AZD1775) in recurrent uterine serous carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6009-6009
Author(s):  
Joyce F. Liu ◽  
Niya Xiong ◽  
Susana M. Campos ◽  
Alexi A. Wright ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Serous Carcinoma ◽  
Clinical Activity ◽  
Targeted Next Generation Sequencing ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response ◽  
Uterine Serous Carcinoma ◽  
Grade 3

6009 Background: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma characterized by TP53 mutations ( > 90%), often concomitantly with oncogenic mutations or amplifications that can increase replication stress. As such, USC may therefore be uniquely sensitive to further interference of cell cycle regulation by Wee1 inhibition. This two-stage single arm Phase 2 study was conducted to assess the activity of the Wee1 inhibitor adavosertib as monotherapy in recurrent USC. Methods: Women with recurrent USC (defined as non-carcinosarcoma uterine cancers with any serous component) were eligible. Patients (pts) were required to have had at least one prior platinum-based chemotherapy regimen; those with known MSI-H/MMRd disease were required to have received prior PD1/PDL1 therapy or to be ineligible for such therapy. There was no upper limit on the number of prior lines pts could have received. All pts were required to have RECIST measurable disease. Pts received adavosertib 300mg daily on days 1 through 5 and 8 through 12 of a 21-day cycle. Coprimary endpoints were objective response and progression-free survival at 6 months (PFS6). Results: Between OCT-11-2018 and SEP-30-2019, 35 pts enrolled on study. Median follow-up is 4.6 months. The median number of prior lines was 3 (range 1-8). 34 pts were considered evaluable for response. In these pts, 9 confirmed and 1 unconfirmed responses were observed, for an ORR of 29.4% (95% CI 15.1-47.5%). The PFS at 6 months was 58.7% (95% CI: 39.5-73.7%). The median PFS is 6.1 months and the median duration of response is 9.0 months. Frequently observed Grade 3 or higher related adverse events included neutropenia (32.3%), anemia (20.6%), and fatigue (23.5%). Immunohistochemistry and targeted next-generation sequencing were performed to investigate potential biomarkers of response. Conclusions: Adavosertib monotherapy demonstrates promising clinical activity in women with USC. The observed monotherapy activity is higher than in other diseases, and additional exploration of the biology of Wee1 inhibition in USC is needed. Further studies of adavosertib in this patient population are planned. Clinical trial information: NCT03668340.

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