Uterine Carcinosarcomas: Incidence and Trends in Management and Survival

Arrastia, Concepcion D.; Fruchter, Rachel G.; Clark, Melissa; Maiman, Mitchell; Remy, Jean; Macasaet, Milagros A.; Gates, E. Jason; Maio, Theresa Di; Marzec, Tomasz

doi:10.1006/gyno.1997.4629

Cited by 99 publications

(63 citation statements)

References 14 publications

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“…Indeed, there is evidence that most of these tumors are monoclonal in origin and that the carcinomatous component represents the true driving force of the disease (11). Regardless of their classification, however, the overall prognosis of patients diagnosed with this uncommon disease remains extremely poor (1,2,11). Our group has recently evaluated the genetic fingerprint of high-grade serous papillary uterine and ovarian carcinomas (3,4).…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas

Santin

Bellone

Siegel

et al. 2007

Clinical Cancer Research

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Purpose: To evaluate the expression levels of claudin-3 and claudin-4, the low-and high-affinity receptors, respectively, for the cytotoxic Clostridium perfringens enterotoxin (CPE) in uterine carcinosarcomas and explore the potential for targeting these receptors in the treatment of this aggressive uterine tumor. Experimental Design: We analyzed claudin-3 and claudin-4 receptor expression at mRNA and protein levels in flash frozen and formalin-fixed, paraffin-embedded carcinosarcoma specimens. Recombinant CPE was used as a novel therapy against chemotherapy-resistant carcinosarcoma cell lines in vitro.The therapeutic effect of sublethal doses of CPE was studied in severe combined immunodeficient mouse xenografts harboring large s.c. carcinosarcomas. Results: All flash-frozen carcinosarcoma biopsies (12 of 12) and short-term carcinosarcoma cell lines evaluated overexpressed claudin-3 and claudin-4 by quantitative reverse transcription-PCR. Membranous immunoreactivity for claudin-4 protein expression was documented in 80% (20 of 25) of primary tumors and 100% (6 of 6) of the metastatic carcinosarcomas, whereas negligible staining was found in normal endometrial cells. Regardless of their resistance to chemotherapeutic agents, all short-term carcinosarcoma cell lines tested died within 1h of exposure to 3.3 Ag/mL of CPE in vitro. Intratumoral injections of well-tolerated doses of CPE in large s.c. carcinosarcoma xenografts led to large areas of tumor cell necrosis and tumor disappearance in all treated animals. Conclusions: Claudin-3 and claudin-4 receptors are highly overexpressed in carcinosarcoma. These proteins may offer promising targets for the use of CPE as a novel type-specific therapy against this biologically aggressive variant of endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

“…They represent the most common of the uterine sarcomas accounting for 1,000 to 1,500 cases annually in the United States (1). They usually arise in elderly postmenopauasal women and, because of their aggressive biological behavior and early spreading pattern, are often diagnosed at advanced stage.…”

mentioning

confidence: 99%

Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas

Santin

Bellone

Siegel

et al. 2007

Clinical Cancer Research

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“…Extended, radical surgery is not routine (12), and the value of pelvic and paraaortic lymphadenectomy has been questioned (7,9). Residual tumor seems to be an important prognostic factor (7,13,14). The benefits of postoperative radiotherapy and chemotherapy are still under debate (5,7,11,(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Prophylactic pelvic irradiation as part of primary therapy in uterine sarcomas

Sorbe¹,

Johansson²

2008

Int J Oncol

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Abstract. In a complete geographic series of 155 cases of primary uterine sarcomas, prophylactic pelvic irradiation was used as standard postoperative therapy in the majority of the cases. Vaginal brachytherapy was also added as a boost. The histology was leiomyosarcoma in 62 cases (40%), carcinosarcoma in 60 (39%), endometrial stromal sarcoma in 25 (16%), and other types in 8 cases (5%). The primary surgery was extended hysterectomy in 11 cases (7%), simple hysterectomy in 110 (71%), and supravaginal hysterectomy in 12 (8%). In 22 cases (14%) no major surgery was possible. In the complete series, 62 recurrences (40%) were recorded. Local (9%), regional (9%), and distant recurrences (28%) were the most frequent. The type of surgery was associated with the risk of tumor recurrence. Extended surgery reduced the risk of local and regional recurrences. The 5-year overall survival rate was 42% and the recurrence-free survival (RFS) was 37%. The number of mitoses was significantly (P=0.007) associated with survival. The locoregional RFS rate was 75% for patients treated with adjuvant irradiation and 83% for patients treated with primary surgery alone. Serious late tissue reactions from the bladder and intestine occurred in 7% of the irradiated cases. The locoregional tumor control rate was high in this series of patients, but no significant difference was found between patients treated with surgery alone and surgery plus postoperative pelvic irradiation. This was true for all histological subtypes of the uterine sarcomas. However, this was not a randomized study and selection bias cannot be ruled out.

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“…Uterine sarcomas are rare, accounting for only 3–5% of all malignant uterine neoplasms [1, 2]. Traditionally, uterine sarcomas have been classified into 3 main histologic subgroups, in order of decreasing incidence: carcinosarcoma (CS), leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS).…”

Section: Introductionmentioning

confidence: 99%

Prognoses and Prognostic Factors of Carcinosarcoma, Endometrial Stromal Sarcoma and Uterine Leiomyosarcoma: A Comparison with Uterine Endometrial Adenocarcinoma

et al. 2006

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Aims: The aims of this study were to evaluate the factors affecting prognosis in patients with uterine sarcomas and to demonstrate that carcinosarcoma bears a similarity to high-grade endometrial carcinoma in terms of its prognosis and clinicopathological parameters. Methods: In June 2004, 17 Japanese institutions received questionnaires regarding uterine sarcomas. Study patients had uterine sarcomas initially treated at each institution between January 1990 and May 2004. Survival analyses and comparisons were performed by univariate methods. Patient data of 921 cases of endometrial adenocarcinoma were also analyzed and compared to the data with the uterine sarcomas. Results: One hundred twenty-one patients with uterine sarcomas were identified who met study eligibility criteria. In uterine sarcomas, carcinosarcoma had a worse prognosis than other sarcomas, but the difference was not significant (p = 0.302). In carcinosarcoma, significant differences were observed with age (p = 0.0388), stage (p < 0.01) and surgical procedure (with or without pelvic lymphadenectomy, p = 0.0316). In carcinosarcoma and G3 adenocarcinoma, no significant difference was identified with regard to overall survival in univariate (p = 0.191) and multivariate (p = 0.168) analyses. Conclusion: Our results demonstrate that the clinical behavior of carcinosarcoma strongly resembles that of G3 endometrial adenocarcinoma, setting it apart from other ‘pure’ uterine sarcomas.

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Uterine Carcinosarcomas: Incidence and Trends in Management and Survival

Cited by 99 publications

References 14 publications

Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas

Overexpression of Clostridium perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Uterine Carcinosarcomas

Prophylactic pelvic irradiation as part of primary therapy in uterine sarcomas

Prognoses and Prognostic Factors of Carcinosarcoma, Endometrial Stromal Sarcoma and Uterine Leiomyosarcoma: A Comparison with Uterine Endometrial Adenocarcinoma

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