Skp2 Protein Expression in Soft Tissue Sarcomas

2003 ◽  
Vol 21 (4) ◽  
pp. 722-727 ◽  
Author(s):  
Andre M. Oliveira ◽  
Scott H. Okuno ◽  
Antonio G. Nascimento ◽  
Ricardo V. Lloyd

Background: p45 S phase kinase-associated protein-2 (p45skp2), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCFskp2). The latter has been implicated in the ubiquitination and degradation of p27kip1 (p27) and G1-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated. Methods: Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were studied in 182 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. Results: The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (≥ 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P = .002) and Ki-67 proliferative index (r = 0.44; P < .0001), but not with p27 expression (r = −0.02; P = .80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival. Conclusion: These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors.

2013 ◽  
Vol 31 (13) ◽  
pp. 1649-1655 ◽  
Author(s):  
Alessandro Gronchi ◽  
Rosalba Miceli ◽  
Elizabeth Shurell ◽  
Fritz C. Eilber ◽  
Frederick R. Eilber ◽  
...  

Purpose Integration of numerous prognostic variables not included in the conventional staging of retroperitoneal soft tissue sarcomas (RPS) is essential in providing effective treatment. The purpose of this study was to build a specific nomogram for predicting postoperative overall survival (OS) and disease-free survival (DFS) in patients with primary RPS. Patients and Methods Data registered in three institutional prospective sarcoma databases were used. We included patients with primary localized RPS resected between 1999 and 2009. Univariate (Kaplan and Meier plots) and multivariate (Cox model) analyses were carried out. The a priori chosen prognostic covariates were age, tumor size, grade, histologic subtype, multifocality, quality of surgery, and radiation therapy. External validation was performed by applying the nomograms to the patients of an external cohort. The model's discriminative ability was estimated by means of the bootstrap-corrected Harrell C statistic. Results In all, 523 patients were identified at the three institutions (developing set). At a median follow-up of 45 months (interquartile range, 22 to 72 months), 171 deaths were recorded. Five- and 7-year OS rates were 56.8% (95% CI, 51.4% to 62.6%) and 46.7% (95% CI, 39.9% to 54.6%. Two hundred twenty-one patients had disease recurrence. Five- and 7-year DFS rates were 39.4% (95% CI, 34.5% to 45.0%) and 35.7% (95% CI, 30.3% to 42.1%). The validation set consisted of 135 patients who were identified at the fourth institution for external validation. The bootstrap-corrected Harrell C statistics for OS and DFS were 0.74 and 0.71 in the developing set and 0.68 and 0.69 in the validating set. Conclusion These nomograms accurately predict OS and DFS. They should be used for patient counseling in clinical practice and stratification in clinical trials.


Author(s):  
Eva-María García-Fontán ◽  
Miguel-Ángel Cañizares-Carretero ◽  
Montserrat Blanco-Ramos ◽  
Jose-María Matilla-González ◽  
Rommel Carrasco-Rodríguez ◽  
...  

Abstract OBJECTIVES Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the importance of different histopathological factors in their prognosis. METHODS Multicentre cooperative group EMETNE prospectively reviewed 153 patients operated on between 1998 and 2016 with diagnosis of atypical carcinoids. Clinical variables and histopathological features were assessed. RESULTS Mean age was 54.36 years, similar for both genders. Concerning pathological study, mean tumour size was 31.7 mm. Rosettes were presented in 17% of the cases and tumoural necrosis in 23.3%. The cell proliferation factor Ki-67 index was 10.7%. The 2- and 5-year overall survival rates were 95.8% and 88.9%, respectively. In the univariate study, statistically significant differences in survival were found for each of the categories of T, N and M factors. Mitotic index and quantification of expression of Ki-67 showed influence in overall survival, although without statistical significance. In the multivariate analysis, factors N, M and mitotic index behaved as independent prognostic factors related to survival. Median disease-free interval in the series was 163.35 months. In cases with loco-regional recurrence, 53% had positive hiliar or mediastinal nodal involvement at the time of the surgery. In the univariate analysis, we observed statistically significant differences in disease-free interval in patients with nodal involvement (P = 0.024) and non-anatomical resections (P = 0.04). Histological characteristics showed no statistically significant differences in disease-free interval. CONCLUSIONS Lymph node involvement, the development of distant metastasis and mitotic index, more than Ki-67 determination, were shown as independent prognostic factors related to survival of these patients.


2006 ◽  
Vol 92 (2) ◽  
pp. 92-97 ◽  
Author(s):  
Sergio Frustaci ◽  
Massimiliano Berretta ◽  
Alessandro Comandone ◽  
Ettore Bidoli ◽  
Antonino De Paoli ◽  
...  

Aims and Background After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice. Methods A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 μg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles. Results From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively. Conclusions The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.


Hand ◽  
2016 ◽  
Vol 12 (5) ◽  
pp. 493-500 ◽  
Author(s):  
Matthew T. Houdek ◽  
Brian E. Walczak ◽  
Benjamin K. Wilke ◽  
Sanjeev Kakar ◽  
Peter S. Rose ◽  
...  

Background: Soft tissue sarcomas (STS) of the hand are exceedingly rare. The aim of this study was to review our institution’s experience with STS of the hand to identify factors affecting outcomes and survivorship. Methods: We retrospectively reviewed the records of 46 hand STS treated with definitive surgery at our institution between 1992 and 2013. Pertinent demographics as well as information regarding the surgical procedure, and disease status at latest follow-up were reviewed. Mean age at diagnosis was 38 years with a mean follow-up of 5 years. Results: The most common tumor subtypes were epithelioid (n = 10) and synovial sarcoma (n = 8). Sixty-one percent were superficial in location. Thirty-three patients had had a nononcologic resection prior to definitive surgical treatment at our institution. Ultimately, negative margins were obtained in all cases. Local recurrence was observed in 5 patients and distant metastases in 14 patients. Tumor sizes ≥2 cm, American Joint Committee on Cancer (AJCC) grade, and depth of the tumor were found to adversely affect the outcome in terms of disease-free and overall survival. Reexcision of an inadvertently excised tumor at an outside institution did not adversely affect the outcome. The 10-year overall and disease-free survival was 72% and 63%. Conclusions: Local recurrence after a wide excision was observed infrequently; however, distant disease was relatively common. Tumors with a size ≥2 cm were associated with a worse disease-free and overall survival, highlighting the aggressive nature of these tumors.


2020 ◽  
Author(s):  
Kyoung Min Kim ◽  
Usama Khamis Hussein ◽  
See-Hyoung Park ◽  
Young Jae Moon ◽  
Zhongkai Zhang ◽  
...  

Abstract BackgroundIL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited. MethodsThis study investigated the expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. ResultsIn human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001). ConclusionsThis study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kyoung Min Kim ◽  
Usama Khamis Hussein ◽  
See-Hyoung Park ◽  
Young Jae Moon ◽  
Zhongkai Zhang ◽  
...  

Abstract Background IL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited. Methods This study investigated the immunohistochemical expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. Immunohistochemical staining for IL4Rα and IL13Rα1 were scored according to a combination of staining intensity and staining area in tissue microarray samples. Positivity for the immunohistochemical expression of IL4Rα and IL13Rα1 were determined using receiver operating curve analysis. Statistical analysis was performed using regression analysis and a chi-square test. Results In human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001). Conclusions This study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.


Author(s):  
Cecilia Tetta ◽  
Maria Carpenzano ◽  
Areej Tawfiq J Algargoush ◽  
Marwah Algargoosh ◽  
Francesco Londero ◽  
...  

Background: Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Introduction: We performed a literature review to evaluate outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). Method: After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. Results: The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. : In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease-free interval from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. : Local control showed high percentage for both procedures. Conclusion: SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and in patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. : Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.


1994 ◽  
Vol 86 (7) ◽  
pp. 549-554 ◽  
Author(s):  
Marija Drobnjak ◽  
Esther Latres ◽  
Daphna Pollack ◽  
Martin Karpeh ◽  
Maria Dudas ◽  
...  

Author(s):  
Kunhi Mohammed K. P. ◽  
Snehasis Pradhan ◽  
Supratim Bhattacharyya ◽  
Prafulla Kumar Das ◽  
Muhammed Navas N. K.

Background: Soft tissue sarcomas are a rare and heterogeneous group of malignant tumors of mesenchymal origin that comprise less than 1 percent of all adult malignancies. Although they occur anywhere in the body, they involve most commonly in extremities, trunk, retroperitoneum and head and neck. The aim of the study was to analyze clinical and histopathological features of various soft tissue sarcomas.Methods: This was a retrospective study, conducted in tertiary cancer centre in Odisha during the period 2015 to 2018. We collected clinical parameters like age, sex, site of swelling, any associated pain and biopsy reports and these variables were correlated with final histopathology reports.Results: A total of 107 patients were included in the study, with male to female ratio of 2:1(71 and 36) and average age of 43.45 years. All of them presented with a swelling. The lower extremities were the most common sites i.e. 44.62%. Pleomorphic sarcoma was the most frequent histologic variety comprising 43% and less frequent variety were angiosarcoma, and myxoid sarcoma.Conclusions: Soft tissue sarcoma are predominant in males and middle aged population are frequently affected. Most common affected site is lower extremity and pleomorphic sarcoma is the prominent histologic type.


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