Overexpression of the osteopontin correlates with the aggressiveness of endometrial cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16048-16048
Author(s):  
C. Cho ◽  
S. Cha ◽  
S. Kwon ◽  
Y. Kwon ◽  
S. Kang ◽  
...  

16048 Background: To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of endometrial cancer. Methods: The status of OPN expression in benign and malignant endometrial cancer cell lines and tissues was analyzed by real time PCR, Western blot, and immunohistochemistry. Nonparametric Spearman's correlation coefficient method was used to assess the statistical significance of the correlation between clinicopathologic characteristics of tumor and OPN expression. Results: An increased expression of OPN was observed in the endometrial cancer compared to normal endometrial tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign endometrial hyperplasia was slightly increased at 1.2, whereas the OPN level in the highly malignant endometrial carcinoma tissue was greatly increased by nearly 3–5 folds. Amongst the 160 cases examined immunohistochemically, of the 43 grade 1 endometrial carcinomas, 31 were unstained and 12 stained weakly positive (+). For the 41 grade 3 or serous type endometrial carcinomas analyzed, 25 (60%) stained strongly positive (+++), 8 (19%) stained moderately positive (++) and 4 (9%) stained weakly positive (+). These results showed that the level of OPN expressed between grade 1 and grade 3 or more was significantly different (Spearman's correlation coefficient method, p = 0.001). However, Kaplan-Meier survival analysis showed that the increased level of OPN expression was not significantly associated with reduced survival time of the patients. Conclusion: The results suggest that the increased OPN level may be involved in the malignant transformation of endometrial adenocarcinoma cells. No significant financial relationships to disclose.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5038-5038
Author(s):  
C. Cho ◽  
S. Kwon ◽  
S. Ramachandran ◽  
S. Kwon ◽  
K. Kwon ◽  
...  

5038 Background: To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of endometrial cancer. We studied OPN expression in endometrial cell carcinomas and correlated OPN expression levels with clinicopathologic tumor features. Methods: The status of OPN expression in benign and malignant endometrial cancer cell lines and tissues was analyzed by Western blot and immunohistochemistry. Nonparametric Spearman’s correlation coefficient method was used to assess the statistical significance of the correlation between clinicopathologic characteristics of tumor and OPN expression. Results: An increased expression of OPN was observed in the endometrial cancer compared to normal endometrial tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign endometrial hyperplasia was slightly increased at 1.2, whereas the OPN level in the highly malignant endometrial carcinoma tissue was greatly increased by nearly 3- 5 folds. Amongst the 70 cases examined immunocytochemically, of the 23 grade 1 endometrial carcinomas, 6 were unstained and 12 stained weakly positive (+). For the 20 grade 3 or serous type endometrial carcinomas analyzed, 8 (40%) stained strongly positive (+++), 8 (40%) stained moderately positive (++) and 1 stained weakly positive (+). These results showed that the level of OPN expressed between grade 1 and grde 3 or more was significantly different (Spearman’s correlation coefficient method, p = 0.001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly associated with reduced survival time of the patients. Conclusions: The results suggest that the increased OPN level may be involved in the malignant transformation of endometrial adenocarcinoma cells and OPN expression level is an important determinant for patient survival. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6087-6087
Author(s):  
Giovanni Scambia ◽  
Sileny N. Han ◽  
Amit M. Oza ◽  
Nicoletta Colombo ◽  
Ana Oaknin ◽  
...  

6087 Background: SAP (TAK-228, MLN0128) is a selective dual inhibitor of mammalian target of rapamycin complexes 1 and 2. In endometrial tumor xenograft models, SAP+PAC exhibited stronger antitumor efficacy than PAC alone. Methods: Female pts with histologic/cytologic diagnosis of endometrial cancer were randomized to receive SAP 4 mg by mouth (days [d] 2–4, 9–11, 16–18, 23–25) plus PAC 80 mg/m2 intravenously (d 1, 8, 15), or PAC alone, in 28-day cycles until unacceptable toxicity or disease progression. Randomization was stratified by histologic subtype, lines of prior chemotherapy (1 vs. 2), and prior taxane therapy. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR; ORR + stable disease), and safety. Additional treatment arms of SAP alone (weekly dosing) and SAP+TAK-117 were closed after futility analyses. Results: 180 pts were randomized to SAP+PAC (n=90) or PAC (n=90); 86 and 87 pts received SAP+PAC and PAC, respectively; 3 pts from each arm were ongoing on treatment at data cut (30 July 2019). Baseline characteristics were balanced between arms. After a median follow-up of 17.2 vs. 14.4 mos with SAP+PAC vs. PAC, median PFS was 5.6 mos vs. 3.7 mos (hazard ratio [HR] 0.82; 95% CI 0.58–1.15). In pts with endometrioid histology (n=116), median PFS was 5.7 mos with SAP+PAC vs 3.3 mos with PAC (HR 0.66; 95% CI 0.43–1.03). In pts with nonendometrioid histology (n=64), median PFS was 3.6 mos with SAP+PAC vs. 5.4 mos with PAC (HR 1.09; 95% CI 0.62–1.90). Median OS was 13.7 mos with SAP+PAC vs. 14.6 mos with PAC (HR 1.01; 95% CI 0.67–1.53). Confirmed ORR was 24% with SAP+PAC vs. 18% with PAC (endometrioid, 23% vs. 16%; nonendometrioid, 28% vs. 22%); CBR was 80% vs. 58% (endometrioid, 84% vs. 55%; nonendometrioid, 72% vs. 63%). Median number of cycles received was 5 (range 1–23) with SAP+PAC and 4 (range 1–37) with PAC. Rates of grade ≥3 treatment-emergent adverse events (TEAEs) were 90% with SAP+PAC vs. 54% with PAC; the most common included anemia (21% vs.12%), neutropenia (12% vs. 3%), fatigue (12% vs. 5%), hypophosphatemia (12% vs. 1%), and pulmonary embolism (11% vs. 3%). Conclusions: Median PFS was longer with SAP+PAC vs. PAC in pts with endometrial cancer but did not reach statistical significance. PFS was particularly longer in the endometrioid subtype but again was not significant, and further studies are warranted. Incidence of grade ≥3 TEAEs was higher with SAP+PAC vs. PAC, but SAP+PAC toxicity was manageable, with no new safety signals. Clinical trial information: NCT02725268.


2010 ◽  
Vol 18 (1-2) ◽  
pp. 38-39
Author(s):  
Christopher Bryant ◽  
Jay Shah ◽  
Sanjeev Kumar ◽  
Adnan Munkarah ◽  
Robert Morris ◽  
...  

The incidence of bone metastases in endometrial cancer is reported to occur in less than 15% of patients with metastatic disease. The medical literature is limited to only case reports, although none describing a sacral recurrence after adjuvant chemo-radiation therapy. We present the case of a 64-year-old woman who underwent surgery for endometrial adenocarcinoma followed by 'sandwich' chemoradiation therapy at our institution, July 2006 (FIGO stage IB grade 3). In spite of adjuvant therapy, which was delivered in August 2008 the patient, developed an isolated sacral recurrence. The optimal therapeutic modality for endometrial cancer patients with high-risk disease remains controversial. The increasing use of combined modality therapy for early stage, high-risk patients may produce different recurrence patterns than described in historical controls.


2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Syeda Sadia Zaidi ◽  
Vipul T. Lakhani ◽  
Oluwole Fadare ◽  
Dineo Khabele

This case report describes a woman treated for stage 1 B grade 3 endometrial adenocarcinoma with surgery and adjuvant radiation therapy who presented 6 months later with pain and symptoms of adrenal insufficiency. A large right adrenal mass revealed adenocarcinoma consistent with the endometrial primary.


2013 ◽  
Vol 23 (7) ◽  
pp. 1252-1257 ◽  
Author(s):  
Onur Guralp ◽  
Susan M. Sheridan ◽  
Josephine Harter ◽  
James Louis Hinshaw ◽  
Songwon Seo ◽  
...  

ObjectiveDuring saline-infused sonohysterography (SIS), the distension fluid is typically discarded. If cytology analysis could identify those patients with endometrial cancer, many women would be spared from further procedures.MethodsThirty consecutive patients with clinical stage I or II endometrial adenocarcinoma were prospectively recruited preoperatively. Saline-infused sonohysterography was performed by instilling 5 mL of saline, withdrawing and sending for analysis. Saline was reinfused until complete SIS images were obtained and sent separately for cytology.ResultsOf the 30 women enrolled, SIS was technically successful in 29. Demographics included mean age (60.5 ± 6.99 years), body mass index (35.55 ± 8.18 kg/m2), endometrioid histology (76%), and grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%), dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology specimens were obtained in 66% of the 5 mL flushes and 72% of the complete SIS collections. Of adequate specimens, the sensitivities to detect endometrial cancer for the 5-mL, complete, and combined fluid samples were 26% (95% confidence interval, 9%–51%), 36% (17%–59%), and 42% (22%–63%). Sensitivity based on the whole study sample (N = 30) was 33% (17%–53%). Statistical significance was not found in the association between a positive test and age, body mass index, grade, diagnostic method, or volume instilled or aspirated.ConclusionsMost patients with early endometrial cancer can undergo SIS procedures with adequate cytology specimens obtained from distention media. However, the sensitivity is low, and refinements are necessary before utilizing as a diagnostic test. In cases with positive results, the patient may be able to avoid other costly and painful procedures.


2008 ◽  
Vol 18 (6) ◽  
pp. 1339-1343 ◽  
Author(s):  
S. Kang ◽  
S. S. Seo ◽  
H. J. Chang ◽  
C. W. Yoo ◽  
S. Y. Park ◽  
...  

In endometrial carcinomas (ECs), previous report suggested that PIK3CA mutations do not coexist with KRAS mutations, but the significant mutual exclusiveness has not been demonstrated. In this study, we examined the mutation frequency of PIK3CA in EC and its mutual exclusiveness with KRAS mutation. We performed mutational analysis of PIK3CA through a polymerase chain reaction single-strand conformation polymorphism assay in 44 cases of endometrial cancer and analyzed the correlation with loss of PTEN, KRAS mutation, and RASSF1A hypermethylation. Somatic mutations of PIK3CA were detected in 14 of 44 (31.8%) of endometrial cancers. In exon 9, seven PIK3CA mutations were located, while seven mutations were located in exon 20. The most common mutation was E545A (35.7%), followed by H1047R (28.6%). Concomitant loss of PTEN expression and PIK3CA mutation was found in four cases of endometrial cancer. KRAS mutations were mutually exclusive with PIK3CA mutations, and those mutations were inversely correlated with statistical significance (P= 0.039). Also, we found that mutations in ERBB2 were mutually exclusive with PIK3CA mutations. RASSF1A and hMLH1 methylation were not correlated with the presence of PIK3CA mutations. PIK3CA was frequently mutated in endometrial cancers. KRAS and PIK3CA mutations are inversely correlated, suggesting that genetic alterations of KRAS and PIK3CA may play equivalent roles in endometrial carcinogenesis.


2018 ◽  
Vol 28 (7) ◽  
pp. 1271-1277
Author(s):  
Rohit Gunan Ganju ◽  
Ossama Tawfik ◽  
Laura Brown ◽  
Allen M. Chen ◽  
Andrea Jewell ◽  
...  

ObjectiveUndifferentiated endometrial carcinoma (UEC) represents a recently recognized and rare diagnosis that is commonly misclassified on histopathologic evaluation. These cancers account for less than 10% of carefully reviewed series of endometrial cancers from academic medical centers. We reviewed a single-institutional experience with the management of UEC focusing on clinicopathologic characteristics and treatment outcomes.MethodsThe medical records of all patients treated for histologically proven endometrial carcinoma between 2007 through 2016 were reviewed. Analysis was limited to 24 consecutive patients with histologically proven endometrial carcinomas that had at least a component of undifferentiated carcinoma on central pathology review. All patients were initially treated by definitive surgical resection. Grade 3 endometrioid carcinomas treated over the same period were used as a control group. The Kaplan-Meier method was used to estimate survival outcomes.ResultsThe median age at diagnosis was 66 years (range, 37–74 years). Ten patients presented with locally advanced or metastatic disease (42%). Fifteen patients (63%) received adjuvant chemotherapy with carboplatin and paclitaxel, 12 patients (50%) received adjuvant pelvic external beam radiation, and 10 patients (42%) received adjuvant vaginal cuff brachytherapy. With a median follow-up of 14 months (range, 0.5–115 months), 4 patients (21%) had developed disease recurrence and/or progression, 2 patients (11%) had died of disease, and 1 patient died of treatment complications. Twelve patients (63%) were alive with no evidence of disease at last contact. Outcomes were comparable to those with grade 3 endometrioid carcinoma.ConclusionsOur data are consistent with prior studies demonstrating that UEC represents a rare clinical entity characterized by high rates of locally advanced disease at presentation. However, survival outcomes appear to be comparable to other high-grade endometrial cancers. Further studies investigating optimal adjuvant therapy in these patients are warranted.


2020 ◽  
Vol 31 (1) ◽  
pp. 78-84
Author(s):  
Melica Nourmoussavi Brodeur ◽  
Vanessa Samouëlian ◽  
Yohann Dabi ◽  
Béatrice Cormier ◽  
Marie-Claude Beauchemin ◽  
...  

BackgroundHistorically, radical hysterectomy followed by adjuvant radiotherapy has been offered to patients with endometrial cancer who have gross cervical involvement; however, this approach is known to carry considerable morbidity. Neoadjuvant radiotherapy followed by extra-fascial hysterectomy has been proposed as an alternative treatment but has been poorly studied to date.ObjectiveTo evaluate the locoregional control rate associated with neoadjuvant radiotherapy followed by extra-fascial hysterectomy.MethodsA retrospective cohort study of 30 patients with endometrial cancer with gross cervical involvement treated between May 2006 and January 2016 was performed. Eligible patients were those aged >18 years with non-metastatic endometrial adenocarcinoma and gross cervical disease treated with curative intent at the Centre hospitalier de l’Université de Montréal. Treatment protocol consisted of pelvic neoadjuvant radiotherapy and high-dose rate brachytherapy followed by extra-fascial hysterectomy. Kaplan-Meier curves were used for survival analysis.ResultsThe median age was 60 (range 37–82) and median body mass index was 32 kg/m2 (range 16–55). Twenty-four (80%) patients were diagnosed with a positive cervical/endocervical biopsy. Clinical staging confirmed 36.7% (n=11) as stage II, 20% (n=6) stage IIIB, 30% (n=9) stage IIIC1, and 13.3% (n=4) stage IIIC2. Seventy-seven per cent (n=23) of patients had an endometrioid histology. Locally advanced disease was identified by imaging alone in six patients. Rates of parametrial, adnexal, vaginal, and nodal invasion were 10% (n=3), 6.7% (n=2), 13.3% (n=4), and 43.3% (n=13) at diagnosis, respectively. All patients completed pelvic radiotherapy (13.3% extended field) and 90% received brachytherapy. Twenty per cent (n=6) of surgeries were performed using minimal invasive technique. On surgical specimen, 63.3% (n=19) had complete cervical response, 90% (n=27) had negative margins, and 10% (n=3) had residual nodal involvement. Median follow-up time was 62 months (range 1–120). Six recurrences were identified; all except one involved distant failure, and two with locoregional failure. Five-year locoregional control rate, disease-free, overall, and disease-specific survival were 90.5%, 78.5%, 92.6%, and 96.2%, respectively. Two patients (6.7%) had grade 3+ acute radiation-related complications (all grade 3). Grade 3+ post-operative morbidity was noted in 2 (6.7%) patients.ConclusionsNeoadjuvant radiotherapy followed by extra-fascial hysterectomy offers good locoregional control with low treatment-related morbidity in patients with endometrial cancer with overt cervical involvement.


2011 ◽  
Vol 30 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Jan Hauke ◽  
Tomasz Kossowski

Comparison of Values of Pearson's and Spearman's Correlation Coefficients on the Same Sets of Data Spearman's rank correlation coefficient is a nonparametric (distribution-free) rank statistic proposed by Charles Spearman as a measure of the strength of an association between two variables. It is a measure of a monotone association that is used when the distribution of data makes Pearson's correlation coefficient undesirable or misleading. Spearman's coefficient is not a measure of the linear relationship between two variables, as some "statisticians" declare. It assesses how well an arbitrary monotonic function can describe a relationship between two variables, without making any assumptions about the frequency distribution of the variables. Unlike Pearson's product-moment correlation coefficient, it does not require the assumption that the relationship between the variables is linear, nor does it require the variables to be measured on interval scales; it can be used for variables measured at the ordinal level. The idea of the paper is to compare the values of Pearson's product-moment correlation coefficient and Spearman's rank correlation coefficient as well as their statistical significance for different sets of data (original - for Pearson's coefficient, and ranked data for Spearman's coefficient) describing regional indices of socio-economic development.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16549-e16549
Author(s):  
Margarita Romeo ◽  
Laia Capdevila ◽  
Sara Cros ◽  
Antoni Tarrats ◽  
Maya Takeuchi ◽  
...  

e16549 Background: The classic adjuvant treatment for high-risk endometrial cancer is RT. Several phase III trials explored the role of CT, as single treatment or added to RT sequentially (ST) or concurrently (CR), but design heterogeneity hampers conclusions. We report the results of a single-institution protocol with adjuvant CT + RT for advanced stages or type II histologies. Key points: (1) ST and CR permitted. (2) CT used pre-, post- and/or during RT: carboplatin AUC 5 + paclitaxel 175 mg/m2 (150 during RT) Q3W, 4-6 cycles (“carbotaxol”). (3) since 2010, cisplatin 50 mg/m2 was used for CR (on day 1 and 28 of RT). CR was preceded/followed by carbotaxol. Methods: All patients (PT) included in the protocol between 1/2005 and 9/2011 were retrospectively revised. Endpoints were survival and toxicity grade 3-4. Kaplan Meier and Fisher test were used. Conclusions: CR-carbotaxol showed a longer progression-free and overall survival than ST without reaching statistical significance (log rank, p= 0.14 and p=0.33). Median survivals with CR-cisplatin were not reached because of shorter follow-up. Statistical differences in toxicities were not found. In the CR-carbotaxol arm, 5 PT had grade 3-4 acute diarrhoea vs none in the others. [Table: see text]


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